EpiGene
Gene OMIM gene Disease OMIM phenotype Pubmed Seizure Phenotype description Key metabolic tests/metabolites
Gene OMIM gene Disease OMIM phenotype Pubmed Seizure Phenotype description Key metabolic tests/metabolites
AAAS 605378 ACHALASIA-ADDISONIANISM-ALACRIMA SYNDROME; AAAS 231550 16264411 3 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Head and Neck Head HP:0000252 (microcephaly)
Eyes HP:0000522 (alacrima)
HP:0009916 (anisocoria) due to HP:0002459 (Dysautonomia)
HP:0000648 (optic atrophy)
Cardiovascular - Abnormal cardiovascular reflexes due to HP:0002459 (Dysautonomia)
HP:0001278 (postural hypotension)
Abdomen Gastrointestinal HP:0002571 (achalasia)
Skin, Nails, Hair Skin HP:0000953 (hyperpigmentation)
HP:0010765; HP:0007556 (hyperkeratosis of the palms and soles)
HP:0000971 (Abnormalities of sweating) due to HP:0002459 (Dysautonomia)
Muscle, Soft Tissue - HP:0002460 (distal muscle weakness) and atrophy
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
HP:0001251 (ataxia)
HP:0001249 (Intellectual disability)
HP:0001347 (Hyperreflexia)
HP:0003487 (Extensor plantar responses)
HP:0001260 (Dysarthria)
HP:0000649 (Abnormal visual evoked potentials)
HP:0003324 (Muscle weakness)
HP:0002459 (Dysautonomia)
HP:0000971 (Abnormalities of sweating)
HP:0001278 (postural hypotension)
HP:0009916 (anisocoria)
Peripheral Nervous System HP:0007002 (Motor neuropathy)
Endocrine Features - Adrenocorticotropic hormone (ACTH)-resistant HP:0000846 (Adrenal insufficiency)
HP:0008220 (Glucocorticoid insufficiency)
HP:0004319 (Mineralocorticoid insufficiency) (in 15%)
Laboratory Abnormalities - Schirmer test shows HP:0000522 (alacrima)
Miscellaneous - Onset in early childhood
HP:0003676 (Progressive disorder)
HP:0000846 (Adrenal insufficiency) usually develops later (first decade)
Neurologic symptoms may develop decades later
Variable neurologic phenotype
 
AARS 601065 EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 29; EIEE29 616339   1 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Other HP:0001511 (Intrauterine growth retardation)
HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000252 (microcephaly) (-4 SD)
Eyes HP:0000643 (Blepharospasm)
HP:0000639 (Nystagmus)
Mouth Orobuccal HP:0100660 (dyskinesia)
Abdomen Gastrointestinal Gastrointestinal reflux
Skeletal Pelvis congenital HP:0002827 (Hip dislocations)
Feet Vertical tali
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System HP:0004319 (nonprogressive encephalopathy)
HP:0001263 (Delayed psychomotor development), profound
HP:0002072 (Chorea)
HP:0007325 (generalized dystonia)
HP:0001257 (Spasticity)
HP:0002123 (Myoclonic seizures), refractory
HP:0002069 (Tonic-clonic seizures)
Diffuse slow background activity seen on EEG
Multifocal polyspike and slow-wave discharges
High-amplitude paroxysmal fast activity
HP:0002283 (global brain atrophy), progressive
HP:0003429 (Hypomyelination)
Peripheral Nervous System HP:0009830 (Peripheral neuropathy)
HP:0001284 (Areflexia)
Miscellaneous - HP:0003577 (Onset at birth)
Seizure onset in first months of life
 
ABAT 137150 GABA-TRANSAMINASE DEFICIENCY #613163   1,5 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height Accelerated linear growth (in 1 of 2 patients)
Head and Neck Face HP:0000278 (Retrognathia), mild (in 1 of 2 patients)
Eyes HP:0000494 (Downslanting palpebral fissures) (in 1 of 2 patients)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early), severe
Neurologic Central Nervous System HP:0001263 (global developmental delay), severe
Seizures, refractory
HP:0001347 (Hyperreflexia)
Tonic posturing
HP:0001254 (Lethargy)
HP:0002415 (Leukodystrophy) (in 1 of 2 patients)
HP:0001274 (agenesis of corpus callosum) (in 1 of 2 patients)
HP:0001321 (Cerebellar hypoplasia) (in 1 of 2 patients)
HP:0002536 (Abnormal gyri) (in 1 of 2 patients)
HP:0007291 (Posterior fossa cyst) (in 1 of 2 patients)
Voice - High-pitched cry
Laboratory Abnormalities - Increased gamma-aminobutyric acid in plasma, urine, and cerebrospinal fluid (CSF)
Increased beta-alanine (in 1 of 2 patients)
Increased growth hormone (in 1 of 2 patients)
Decreased hepatic GABA transaminase activity
Early death
Molecular Basis - Caused by mutation in the 4-aminobutyrate aminotransferase gene (ABAT, 137150.0001)
Increased gamma-aminobutyric acid (P, U, C)
Increased beta-alanine
ABCC8 600509 HYPOGLYCEMIA, LEUCINE-INDUCED; LIH 240800   3 Inheritance - HP:0000006 (Autosomal dominant)
Growth Weight HP:0001520 (large for gestational age) (in some patients)
Head and Neck Eyes HP:0000486 (Strabismus), alternating (in some patients)
Abdomen Pancreas HP:0004510 (Islet cell hyperplasia)
Neurologic Central Nervous System HP:0002173 (Hypoglycemic seizures)
HP:0000737 (Irritability)
HP:0002329 (Drowsiness)
HP:0001252 (muscle hypotonia)
Staring
Coma
HP:0001249 (Intellectual disability)
HP:0002131 (episodic ataxia)
HP:0001257 (Spasticity)
HP:0001347 (Increased deep tendon reflexes)
Metabolic Features - HP:0001943 (Hypoglycemia), leucine-induced
HP:0001943 (Hypoglycemia), oral protein-induced
Endocrine Features - Hyperinsulinemic HP:0001943 (Hypoglycemia)
Laboratory Abnormalities - Intermittent severe HP:0001943 (Hypoglycemia) (in some patients)
Hypoglycemia
Hyperinsulinemia
ABCD1 300371 ADRENOLEUKODYSTROPHY; ALD 300100   5 Inheritance - HP:0001419 (X-linked recessive)
Head and Neck Ears HP:0000410 (Hearing loss, mixed)
Eyes HP:0000572 (Visual loss)

Abdomen Gastrointestinal HP:0002607 (Fecal incontinence)

Genitourinary External Genitalia (Male) HP:0000802 (Impotence)
Bladder HP:0000020 (Urinary incontinence)

Neurologic Central Nervous System HP:0002180 (Neurodegeneration), progressive
HP:0001268 (cognitive decline)
HP:0002371 (Loss of speech)
HP:0000726 (Dementia)
HP:0001283 (Bulbar palsy)
Seizures
HP:0002385 (Paraparesis)
HP:0001257 (Spasticity)
HP:0002311 (Incoordination)
HP:0001251 (ataxia)
HP:0002500 (White matter abnormalities)
Cerebral HP:0007305 (CNS demyelination) and inflammation
Peripheral Nervous System Sensory loss
Distal axonopathy (adrenomyeloneuropathy)
Behavioral Psychiatric Manifestations Behavioral changes
HP:0007018 (HP:0007018 (Attention deficit hyperactivity disorder)-hyperactivity disorder)
HP:0000729 (autistic behaviour)
HP:0000709 (Psychosis)

Endocrine Features - HP:0000846 (Adrenal insufficiency) (Addison disease)
Laboratory Abnormalities - Systemic accumulation of very long chain fatty acids (VLCFA)
Miscellaneous - HP:0003812 (Variable phenotype), ranging from asymptomatic to death by age 3 years
Onset ranges from childhood (severe phenotype) to adulthood (limited phenotype)
HP:0003676 (Progressive disorder)
Heterozygous female carriers may manifest symptoms
Estimated incidence of 1 in 17,000
Very long chain fatty acids (P, U, C)
ACADM 607008 ACYL-CoA DEHYDROGENASE, MEDIUM-CHAIN, DEFICIENCY OF; ACADMD 201450   2 Inheritance - HP:0000007 (Autosomal recessive)
Abdomen Liver HP:0002240 (Hepatomegaly)
HP:0001397 (Fatty infiltration of liver)
Gastrointestinal HP:0002013 (Vomiting)

Neurologic Central Nervous System HP:0001254 (Lethargy)
Seizures
Coma
HP:0002181 (Cerebral edema)
HP:0012758 (neurodevelopmental delay) if undiagnosed or untreated
HP:0008947 (Hypotonia, early)

Metabolic Features - Absent to trace urine and plasma ketones
Mild HP:0001942 (metabolic acidosis)
HP:0001943 (Hypoglycemia)
Laboratory Abnormalities - Mildly HP:0001987 (hyperammonemia)
HP:0002910 (Increased liver enzymes)
Medium chain HP:0003215 (dicarboxylic aciduria)
Decreased plasma carnitine
Acylglycinuria
Deficiency of medium-chain acyl-CoA dehydrogenase
Miscellaneous - Most common disorder of fatty acid oxidation (1/13,000 births)
Clinical presentation varies from asymptomatic to fulminant course
Onset precipitated by fasting or illness
Medium chain dicarboxylic aciduria
Decreased carnitine (P)
Acylglycinuria
Absent to trace urine and plasma ketones
Hypoglycemia
ACADS 606885 ACYL-CoA DEHYDROGENASE, SHORT-CHAIN, DEFICIENCY OF; ACADSD 201470   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other Chronic HP:0001508 (Failure to thrive)
Head and Neck Face Facial HP:0003324 (Muscle weakness)
EyesExternal HP:0000544 (Ophthalmoplegia), progressive (rare)
Cardiovascular Heart HP:0001638 (Cardiomyopathy) (rare)
Abdomen Gastrointestinal HP:0011968 (feeding difficulties)
Skeletal - HP:0004576 (large joint contractures)
Spine HP:0002650 (Scoliosis)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
HP:0003324 (Muscle weakness)
HP:0003756 (Myopathy)
Multiminicore HP:0003756 (Myopathy)
Lipid storage HP:0003756 (Myopathy)
Neurologic Central Nervous System HP:0008947 (Hypotonia, early)
HP:0012758 (neurodevelopmental delay)
HP:0000750 (Speech delay)
HP:0001254 (Lethargy)
Seizures
HP:0002500 (White matter abnormalities) (uncommon)
Behavioral Psychiatric Manifestations HP:0000709 (Psychosis) (rare)
Metabolic Features - Acute metabolic decompensation
HP:0001942 (metabolic acidosis), episodic
Laboratory Abnormalities - Ethylmalonic aciduria
Methylsuccinic aciduria
Decreased SCAD activity
Increased serum acyl carnitines
Increased serum butyryl carnitine
Miscellaneous - Onset birth to early childhood
HP:0003812 (Variable phenotype), ranging from asymptomatic to severe
Ethylmalonic aciduria
Methylsuccinic aciduria
Increased butyryl carnitine (P)
ACAT1 607809 ALPHA-METHYLACETOACETIC ACIDURIA 203750   3 Inheritance - HP:0000007 (Autosomal recessive)
Abdomen Gastrointestinal HP:0002013 (Vomiting)
Neurologic Central Nervous System HP:0001249 (Intellectual disability) (in some cases)
Metabolic Features - HP:0001993 (ketoacidosis), episodic
HP:0001944 (Dehydration)
Laboratory Abnormalities - Increased urinary 2-methyl-3-hydroxybutyric acid
Increased urinary 2-methylacetoacetic acid
Increased urinary tiglylglycine
Increased urinary 2-butanone
Miscellaneous - Onset at 5-24 months
Infections may precipitate ketotic episodes
Patients with T2 deficiency and urinary abnormalities may be asymptomatic
Ketoacidosis, episodic
2-Ethylhydracrylic acid (U)
2-Methyl-3-hydroxybutyric acid (U)
2-Methyl-3-hydroxy-butyrylcarnitine (P, B)
2-Methylacetoacetic acid (U)
3-Hydroxy-n-butyric acid (U, B)
Dicarboxylic acids (U)
ACMSD 608889 Cortical myoclonus, epilepsy and parkinsonism   23955123 2 0 0
ACO2 100850 INFANTILE CEREBELLAR-RETINAL DEGENERATION; ICRD 614559   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Weight HP:0004325 (Low weight)
Other HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000252 (microcephaly), progressive
Ears HP:0000407 (sensorineural hearing loss) (in 2 patients)
Eyes HP:0000556 (Retinal dystrophy)
HP:0000648 (optic atrophy)
HP:0000486 (Strabismus)
Abnormal pursuit
HP:0000639 (Nystagmus)
Muscle, Soft Tissue - Decreased glutamate oxidation (about 63% of normal)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development), severe
HP:0001249 (Intellectual disability), severe to profound
Only some achieve rolling or sitting
HP:0001251 (ataxia)
Seizures
HP:0002305 (Athetosis)
Head bobbing
HP:0008947 (Hypotonia, early)
HP:0002120 (Cortical atrophy), progressive
HP:0001272 (Cerebellar atrophy), progressive
HP:0002079 (Thin corpus callosum)
HP:0002500 (White matter abnormalities)
Peripheral Nervous System HP:0001265 (Hyporeflexia)
HP:0001284 (Areflexia)
HP:0007108 (demyelinating peripheral neuropathy)
Miscellaneous - HP:0003593 (Onset in infancy)
0
ACOX1 609751 PEROXISOMAL ACYL-CoA OXIDASE DEFICIENCY 264470   5 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000248 (Brachycephaly)
Face HP:0002007 (Frontal bossing)
Ears HP:0000407 (sensorineural hearing loss), bilateral
HP:0000369 (Low-set ears)
Eyes HP:0000639 (Nystagmus)
HP:0000486 (Strabismus)
HP:0000316 (Hypertelorism), mild
HP:0000648 (optic atrophy)
HP:0000547 (Tapetoretinal degeneration)
HP:0000580 (Pigmentary retinopathy)
Flattened or absent electroretinogram (ERG)
HP:0007965 (undetectable visual evoked potentials) (VER)
Nose HP:0007965 (Broad nasal bridge)
HP:0005280 (depressed nasal bridge)
Chest External Features HP:0003186 (Inverted nipples) (uncommon)
Abdomen Liver HP:0002240 (Hepatomegaly), mild
HP:0001397 (Liver steatosis), diffuse
Liver biopsy shows normal numbers of enlarged peroxisomes
HP:0002910 (HP:0002910 (abnormal liver enzymes) tests)
Gastrointestinal HP:0002015 (Dysphagia)
Neurologic Central Nervous System HP:0008947 (Hypotonia, early), neonatal
Seizures
EEG shows epileptiform discharges
HP:0001263 (Delayed psychomotor development)
HP:0001268 (Cognitive decline)ion after age 2 years
HP:0001276 (Muscle hypertonia) (after age 2 years)
HP:0001249 (Intellectual disability), severe
HP:0007256 (Pyramidal tract signs)
HP:0007325 (generalized dystonia)
HP:0003487 (Extensor plantar responses)
Brain imaging shows white-matter hypodensities and HP:0007305 (CNS demyelination)
HP:0002415 (Leukodystrophy)
Behavioral Psychiatric Manifestations HP:0008763 (No social interaction)
HP:0000737 (Irritability)
Stereotypical movements
Laboratory Abnormalities - Increased plasma levels of very-long chain fatty acids (VLCFA)
Decreased or absent peroxisome acyl-CoA oxidase activity and protein
Normal serum plasmalogen
Miscellaneous - HP:0003593 (Onset in infancy)
HP:0002344 (Neurologic deterioration) is severe after age 2 to 2.5 years
Very-long chain fatty acids (P)
Normal serum plasmalogen
ACP5 171640 SPONDYLOENCHONDRODYSPLASIA WITH IMMUNE DYSREGULATION; SPENCDI ?term=ACP5+epilepsy 607944   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Head and Neck Ears HP:0000369 (Low-set ears)
HP:0000388 (Otitis media), multiple episodes
Nose Narrow, pointy nose
Respiratory - HP:0200117 (Recurrent respiratory tract infections) (upper and lower)
Lung HP:0002090 (Pneumonia)
HP:0002091 (Restrictive lung disease)
Interstitial fibrosis
Skeletal - HP:0002657 (Spondylometaphyseal dysplasia)
Spine HP:0000926 (Platyspondyly)
Irregular vertebral endplates
Limbs Sclerotic, HP:0003025 (irregular metaphyses) (distal radii and ulnae, distal femurs, proximal fibulae)
Skin, Nails, Hair Skin HP:0001034 (Hyperpigmented macules)
Hypopigmented skin patches on arms (HP:0001045 (vitiligo)
Hair Normal hair shaft morphology
Neurologic Central Nervous System Normal intelligence
Endocrine Features - HP:0000821 (Hypothyroidism) (autoimmune)
Hematology - HP:0001973 (Idiopathic thrombocytopenic purpura) (ITP)
Immunology - HP:0005387 (combined immunodeficiency)
HP:0002783 (Recurrent infections) (HP:0002090 (Pneumonia), HP:0000246 (sinusitis), fulminant varicella)
HP:0002960 (Autoimmune disorders) (i.e., ITP, juvenile rheumatoid arthritis (JRA), HP:0000821 (Hypothyroidism), Crohn disease)
Decreased T cell response to mitogens
Decreased numbers of circulating T cells
Decreased specific antibodies
Normal to elevated IgG
HP:0002716 (Lymphadenopathy)
 
ACSF3 614245 COMBINED MALONIC AND METHYLMALONIC ACIDURIA; CMAMMA 614265   2 0 Methylmalonic and malonic acid (U) with MMA/MA ratio greater than 5
ACTB 102630 BARAITSER-WINTER SYNDROME 1; BRWS1 243310   2 Inheritance - HP:0000006 (Autosomal dominant)
Growth Height HP:0004322 (short stature)
Height in childhood <5th percentile
Weight Weight in childhood <5th percentile
Other HP:0008897 (Postnatal growth retardation)

Head and Neck Head HP:0005487 (Metopic ridging)
HP:0000243 (Trigonocephaly)
HP:0000252 (microcephaly)
Face HP:0000343 (Long philtrum)
Prominent/full/wide cheeks
HP:0000307 (Pointed chin)
HP:0000278 (Retrognathia) (in some patients)
Ears HP:0000369 (Low-set ears)
HP:0000396 (Overfolded helices)
HP:0000377 (Abnormally shaped ears)
HP:0000407 (sensorineural hearing loss) (in some patients)
Eyes HP:0000508 (Ptosis)
HP:0000316 (Hypertelorism)
Prominent HP:0000286 (Epicanthus)
Iris HP:0000589 (coloboma) (in some patients)
HP:0000567 (Chorioretinal coloboma)
HP:0000568 (Microphthalmia) (rare)
HP:0002553 (Arched eyebrows) (rare)
HP:0000637 (Long palpebral fissures)
Nose HP:0007965 (Broad nasal bridge)
HP:0003196 (Short nose)
HP:0000463 (Upturned nose)
Large, squared nose tip
HP:0000426 (Prominent nasal root) on profile
Mouth HP:0000219 (Thin upper lip)
HP:0000154 (wide mouth)
Thick/prominent/HP:0000179 (Thick lower lip vermilion)
HP:0000202 (HP:0100333 (Unilateral cleft lip)/palate) (in some patients)
Neck HP:0000470 (Short neck)

Cardiovascular Heart HP:0001647 (Bicuspid aortic valve)
HP:0001650 (Aortic stenosis)
Vascular HP:0001643 (Patent ductus arteriosus)

Genitourinary External Genitalia (Male) HP:0000054 (Small penis)
Internal Genitalia (Male) HP:0000028 (Cryptorchidism)

Skeletal Spine HP:0002808 (Kyphosis)/HP:0002650 (Scoliosis) (in some patients)
HP:0000766 (Pectus deformities) (in some patients)
Limbs Limited extension of knees and elbows (in some patients)
Feet HP:0010066 (Duplicated hallux) (rare)

Skin, Nails, Hair Hair HP:0002162 (Low posterior hair line)

Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
HP:0001249 (Intellectual disability)
HP:0008947 (Hypotonia, early)
Seizures
HP:0001274 (Agenesis of corpus callosum)
Focal HP:0001302 (pachygyria)
HP:0001339 (Lissencephaly)
Band HP:0002282 (heterotopia)s (in some patients)
HP:0002119 (ventriculomegaly) (in some patients)
HP:0001257 (Spasticity) of lower limbs (in some patients)

Laboratory Abnormalities - Chromosome inversion - inv2(p12q14) in 2 patients
 
ACTG1 102560 BARAITSER-WINTER SYNDROME 2; BRWS2 614583   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Head HP:0000243 (Trigonocephaly)/HP:0005487 (metopic ridge)
Face Prominent/full/wide cheeks
HP:0000307 (Pointed chin)
HP:0000278 (Retrognathia) (in some patients)
Ears HP:0000377 (Abnormally shaped ears)
Deafness (in some patients)
Eyes HP:0000568 (Microphthalmia) (in some patients)
HP:0002553 (Arched eyebrows)
HP:0000637 (Long palpebral fissures)
Eye HP:0000589 (coloboma) (in some patients)
HP:0000316 (Hypertelorism)/ HP:0000506 (telecanthus)
HP:0000508 (Ptosis)
Nose Short, HP:0000463 (Upturned nose)
Large, squared nose tip
HP:0000426 (Prominent nasal root) on profile
Mouth Thick/prominent/HP:0000179 (Thick lower lip vermilion)
HP:0000202 (HP:0100333 (Unilateral cleft lip)/palate) (in some patients)
HP:0000343 (Long philtrum)
HP:0000219 (Thin upper lip)
HP:0000154 (wide mouth)
Neck HP:0000470 (Short neck) (in some patients)
HP:0000465 (Pterygium colli) (in some patients)
Cardiovascular Heart HP:0002564 (Congenital heart defect) (in some patients)
Skeletal Spine HP:0002808 (Kyphosis) /HP:0002650 (Scoliosis) (in some patients)
HP:0000766 (Pectus deformities) (in some patients)
Neurologic Central Nervous System HP:0002119 (ventriculomegaly) (in some patients)
HP:0001249 (Intellectual disability)
HP:0001302 (pachygyria)/HP:0001339 (Lissencephaly)
HP:0001274 (Agenesis of corpus callosum) (in some patients)
Epilepsy
 
ACVRL1 601284 TELANGIECTASIA, HEREDITARY HEMORRHAGIC, TYPE 2; HHT2 600376   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Eyes HP:0000524 (Conjunctival telangiectases)
Choriocapillaris atrophy
Nose Spontaneous, recurrent HP:0000421 (epistaxis) (onset in childhood)
Nasal mucosa HP:0100579 (Mucosal telangiectases)
Mouth Lip HP:0001009 (Cutaneous telangiectases)
Tongue HP:0100579 (Mucosal telangiectases)
Palate HP:0100579 (Mucosal telangiectases)
Cardiovascular Heart Right-to-left shunt
Vascular HP:0100026 (Arteriovenous malformation) (cerebral, spinal, pulmonary, liver)
Respiratory - HP:0002094 (dyspnea)
Lung Pulmonary HP:0100026 (Arteriovenous malformation) (PAVM)
HP:0000961 (Cyanosis)
A subset of patients develop HP:0002092 (pulmonary arterial hypertension)
Abdomen HP:0001394 (liver cirrhosis)
Liver HP:0100026 (Arteriovenous malformation)
Gastrointestinal HP:0002239 (Gastrointestinal hemorrhage) (onset usually 5th-6th decade)
HP:0000471 Angiodysplasia
HP:0100026 (Arteriovenous malformation)
HP:0100579 (Mucosal telangiectases) (stomach, duodenum, small bowel, colon)
Melena
Hematochezia
Hematemesis
Skin, Nails, Hair Skin HP:0001009 (Cutaneous telangiectases) (especially on tongue, lips, palate, face, conjunctiva, trunk, nail beds, fingers, and finger pads)
Nails Nail bed HP:0001009 (Cutaneous telangiectases)
Neurologic Central Nervous System HP:0002076 (Migraine)
Brain abscess
HP:0002326 (Transient ischemic attack)
Ischemic HP:0001297 (stroke)
Seizure
HP:0001342 (Intracerebral hemorrhage)
HP:0001276 (Subarachnoid hemorrhage)
Cerebral HP:0100026 (Arteriovenous malformation)
Spinal HP:0100026 (Arteriovenous malformation)
Hematology - HP:0001901 (Polycythemia)
HP:0001903 (Anemia)
Miscellaneous - Definite diagnosis if 3/4 criteria present epistaxis, HP:0001009 (Telangiectasia), visceral lesion, or family history)
Genetic heterogeneity (see HHT1 187300)
PAVM more frequent in HHT1 than HHT2
 
ACY1 104620 AMINOACYLASE 1 DEFICIENCY; ACY1D 609924   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Ears HP:0000407 (sensorineural hearing loss)
Eyes HP:0000316 (Hypertelorism)
Nose HP:0000431 (Broad nasal bridge)
Muscle, Soft Tissue - HP:0003324 (Muscle weakness)
HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System Seizures
HP:0001263 (global developmental delay), mild to moderate
Acute HP:0004319 (nonprogressive encephalopathy)
HP:0002283 (global brain atrophy)
HP:0001272 (Cerebellar atrophy)
HP:0012448 (Delayed myelination)
Behavioral Psychiatric Manifestations HP:0000752 (Hyperactivity)
Laboratory Abnormalities - Decreased aminoacylase-1 activity
Increased urinary N-acetylated amino acids
Miscellaneous - HP:0003812 (Variable phenotype)
Some patients are asymptomatic and detected only by newborn screening
Seizures may occur with illness
Patients may show normal development
Increased N-acetylated amino acids (U)
ADAM22 603709 Progressive encephalopathy with cortical atrophy and epilepsy   27066583 1 0  
ADAMTSL2 612277 GELEOPHYSIC DYSPLASIA 1; GPHYSD1 231050   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Normal upper/lower segment ratio
Weight Normal birth weight
Head and Neck Head Normal head circumference
Face HP:0000311 (Round face)
HP:0000343 (Long philtrum), HP:0000319 (smooth philtrum)
'Pleasant, happy-nature' appearance
Ears HP:0000391 (Thickened helices)
Eyes HP:0000582 (Upward slanting palpebral fissures)
Nose HP:0003196 (Short nose)
HP:0000463 (Anteverted nares)
Mouth HP:0000154 (Wide mouth)
Cardiovascular Heart HP:0001635 (Cardiac failure)
HP:0001718 (Mitral stenosis)
HP:0010446 (Tricuspid stenosis)
Vascular HP:0001650 (Aortic stenosis)
Respiratory Airways HP:0002777 (Tracheal stenosis)
Brainstem bronchi stenosis
Chest Ribs, Sternum, Clavicles and Scapulae HP:0000767 (HP:0000766 (Pectus deformities) excavatum)
Abdomen Liver HP:0002240 (Hepatomegaly)
Skeletal - HP:0000938 (Osteopenia)
Skull HP:0002680 (J-shaped sella turcica)
Pelvis HP:0002673 (Coxa valga)
Limbs Shortened long tubular bones
Small, HP:0005041 (irregular capital femoral epiphyses)
Hands HP:0004279 (Short hands)
Wrist HP:0004576 (large joint contractures)
Finger HP:0004576 (large joint contractures)
HP:0010049 (Short metacarpals)with rounded proximal ends
Feet HP:0001773 (Small feet)
Short, plump tubular bones
Skin, Nails, Hair Skin HP:0001072 (Thickened skin)
Tight skin
Nails HP:0001792 (Small nails)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
Seizures
Voice - HP:0001620 (High-pitched voice)
Miscellaneous - Lysosomal storage vacuoles in trachea, liver, cartilage, and heart
 
ADAT3 615302 MENTAL RETARDATION, AUTOSOMAL RECESSIVE 36; MRT36 615286 26842963 2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000252 (microcephaly) (in some patients)
Eyes HP:0000565 (Esotropia)
HP:0000486 (Strabismus)
Neurologic Central Nervous System HP:0001249 (Intellectual disability)
HP:0008947 (Hypotonia, early)
Mild brain anomalies on MRI (e.g., HP:0002119 (Ventriculomegaly) (in some patients)
Miscellaneous - HP:0003593 (Onset in infancy)
0
ADCK3 606980 COENZYME Q10 DEFICIENCY, PRIMARY, 4; COQ10D4 612016   2 Inheritance - HP:0000007 (Autosomal recessive)
Skeletal Feet HP:0001761 (Pes cavus)
Talus valgus
Muscle, Soft Tissue - HP:0003546 (Exercise intolerance)
HP:0008947 (Hypotonia, early)
HP:0003701 (proximal muscle weakness)HP:0003324 (Muscle weakness)
Decreased coenzyme Q
Decreased activity of respiratory complex II+III
Decreased activity of respiratory complex I+III
Muscle biopsy shows mitochondrial aggregates
Muscle biopsy shows lipid droplets
Neurologic Central Nervous System cerebellar HP:0001251 (ataxia)
HP:0001272 (Cerebellar atrophy)
HP:0002322 (Resting tremor) (less common)
HP:0001336 (myoclonus) (less common)
HP:0007256 (Pyramidal tract signs) (less common)
HP:0001263 (global developmental delay), variable (in some patients)
HP:0001249 (Intellectual disability), variable (in some patients)
Seizure (in some patients)
Peripheral Nervous System HP:0001347 (Hyperreflexia)
Metabolic Features - HP:0003128 (Lactic acidosis)
Laboratory Abnormalities - HP:0002151; HP:0002490 (Increased serum and CSF lactate)
Miscellaneous - Onset in early to late childhood
HP:0003828 (Variable severity)
Seizures and cognitive involvement are variable findings
Oral supplementation with ubiquinone does not result in major clinical improvement
Increased lactate (P, C)
ADGRG1 604110 POLYMICROGYRIA, BILATERAL FRONTOPARIETAL; BFPP #606854   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes Dysconjugate gaze
HP:0000565 (Esotropia)
HP:0000639 (Nystagmus)
HP:0000486 (Strabismus)
HP:0000577 (Exotropia)
Muscle, Soft Tissue - HP:0001276 (Hypertonicity)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
HP:0001263 (global developmental delay)
HP:0001249 (Intellectual disability), moderate to severe
HP:0001276 (Hypertonicity)
HP:0001347 (Hyperreflexia)
HP:0003487 (Extensor plantar responses)
Ankle HP:0002169 (Clonus)
Seizures
HP:0001317 (Cerebellar signs)
HP:0007256 (Pyramidal tract signs)
HP:0002136 (Wide-based gait)
Truncal HP:0001251 (ataxia)
Finger HP:0001310 (Dysmetria)
HP:0002126 (Polymicrogyria), most severe in the frontoparietal regions
HP:0002126 (Polymicrogyria), anterior to posterior gradient
Areas of HP:0007266 (Dysmyelination) on MRI
HP:0002365 (Brainstem hypoplasia)
HP:0001321 (Cerebellar hypoplasia)
 
ADGRV1 602851 FEBRILE SEIZURES, FAMILIAL, 4; FEB4 604352   2 Inheritance - HP:0000006 (Autosomal dominant)
Neurologic Central Nervous System HP:0002373 (febrile seizures)
Generalized HP:0002069 (Tonic-clonic seizures)
Hypertonic seizures
Hypotonic seizures
Seizures occur in absence of intracranial infection or defined pathologic or traumatic cause
Seizures usually last less than 15 minutes
Seizures recur in 33% of patients
Patients show normal psychomotor development
Between 2 and 7% of children will develop afebrile seizure disorders later in life
Miscellaneous - Onset 3 months of age up to 5 years
Seizures remit by age 5 years
Genetic heterogeneity (see FEB1 121210)
Mutation in the MASS1 gene has been identified in 1 of 48 families with familial HP:0002373 (febrile seizures) linked to 5q14
 
ADK 102750 HYPERMETHIONINEMIA DUE TO ADENOSINE KINASE DEFICIENCY 614300   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000256 (Macrocephaly)
HP:0002007 (Frontal bossing)
Ears HP:0000407 (sensorineural hearing loss) (in some)
Eyes HP:0000316 (Hypertelorism)
Cardiovascular Heart HP:0001627 (congenital heart defects) (in some)
HP:0001631 (Atrial septal defect)
HP:0001642 (Pulmonary stenosis)
Vascular HP:0001680 (Coarctation of aorta)
Abdomen Liver HP:0001410 (Liver dysfunction), mild
HP:0001397 (Liver steatosis)
HP:0001396 (Cholestasis)
HP:0006580 (Portal fibrosis), mild
Skeletal Hands Slender hands
Feet Slender feet
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
HP:0003202 (Muscle wasting)
Neurologic Central Nervous System Global HP:0012758 (neurodevelopmental delay), severe
HP:0008947 (Hypotonia, early)
Seizures
HP:0000750 (language delay)
HP:0002283 (global brain atrophy)
White matter degeneration
Laboratory Abnormalities - HP:0002910 (HP:0002910 (abnormal liver enzymes) tests)
HP:0002904 (Hyperbilirubinemia)
Hypermethioninemia
Increased serum S-adenosylmethionine
Increased serum S-adenosylhomocysteine
Normal serum homocysteine
Increased urinary adenosine
Miscellaneous - HP:0003593 (Onset in infancy)
HP:0003676 (Progressive disorder)
Hypermethioninemia
Increased S-adenosylmethionine (P)
Increased S-adenosylhomocysteine (P)
Increased adenosine (U)
ADNP 611386 HELSMOORTEL-VAN DER AA SYNDROME; HVDAS 615873   2 Inheritance - HP:0000006 (Autosomal dominant)
Growth Height HP:0004322 (short stature)
Weight HP:0001513 (Obesity)
Head and Neck Head HP:0011220 (Prominent forehead)
Face HP:0000319 (smooth philtrum)
Eyes HP:0000494 (Downslanting palpebral fissures)
Notched eyelid
HP:0000508 (Ptosis)
HP:0000486 (Strabismus)
HP:0000540 (Hypermetropia)
HP:0000505 (Visual impairment)
Nose HP:0007965 (Broad nasal bridge)
HP:0003196 (Short nose)
Mouth HP:0000219 (Thin upper lip)
Cardiovascular Heart HP:0002564 (Congenital heart defect) (less common)
Abdomen Gastrointestinal HP:0011968 (feeding difficulties)
Skeletal - HP:0001388 (Joint laxity)
Hands HP:0200055 (Small hands)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
HP:0012758 (neurodevelopmental delay) apparent in infancy
HP:0001249 (Intellectual disability), mild to severe
HP:0002463 (Language impairment)
Seizures (less common)
Behavioral Psychiatric Manifestations HP:0000729 (autistic behaviour)
HP:0000722 (Obsessive-compulsive behavior)
HP:0000733 (Stereotypic behavior)
HP:0000752 (Hyperactivity)
Immunology - HP:0002783 (Recurrent infections)
Miscellaneous - HP:0003593 (Onset in infancy)
Variable extraneurologic features
 
ADRA2B 104260 EPILEPSY, FAMILIAL ADULT MYOCLONIC, 2; FAME2 607876   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Eyes Eyelid twitching

Neurologic - Involuntary rhythmic myoclonic movements (tremor) of the distal extremities, usually fingers
Movements (tremor) characterized by 8 to 10-Hz discharges
Eyelid twitching
HP:0001336 (myoclonus)
Postural hand HP:0002322 (Resting tremor)
Generalized HP:0002069 (Tonic-clonic seizures)(GTCS), infrequent
HP:0100543 (Cognitive impairment) (in some patients)
EEG shows generalized and focal spike and wave complexes
Photoparoxysmal response on EEG
Electrophysiologic studies indicate cortical origin
Giant somatosensory evoked potentials (SEPs)
Enhancement of the C-reflex
Jerk-locked preHP:0001336 (myoclonus) spikes

Miscellaneous - Adult onset (range 12 to 59 years)
Nonprogressive or slowly progressive
 
ADSL 608222 ADENYLOSUCCINASE DEFICIENCY 103050   1 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0008897 (Postnatal growth retardation)
Head and Neck Head HP:0000248 (Brachycephaly)
HP:0000252 (microcephaly) (less common)
HP:0005487 (Metopic ridging)
Face Long HP:0000319 (smooth philtrum)
Ears HP:0000369 (Low-set ears)
Eyes HP:0000486 (Strabismus)
HP:0000639 (Nystagmus)
Nose HP:0003196 (Small nose)
HP:0000463 (Anteverted nostrils)
Mouth HP:0000219 (Thin upper lip)
HP:0000154 (Wide mouth)
Muscle, Soft Tissue - HP:0003202 (Muscle wasting)
Neurologic Central Nervous System HP:0001263 (global developmental delay), severe
HP:0001249 (Intellectual disability)
HP:0008947 (Hypotonia, early)
HP:0001251 (ataxia)
HP:0002540 (inability to walk)
HP:0000817 (Poor eye contact)
HP:0000750 (language delay)
Seizures, refractory
HP:0001257 (Spasticity)
HP:0002179 (Opisthotonus)
HP:0001336 (myoclonus)
HP:0001348 (Brisk reflexes)
HP:0002283 (global brain atrophy)
HP:0001272 (Cerebellar atrophy)
HP:0003429 (Hypomyelination)
Behavioral Psychiatric Manifestations HP:0000729 (autistic behaviour)
HP:0000752 (Hyperactivity)
HP:0000718 (Aggressive behavior)
Temper tantrums
HP:0000733 (Stereotypic behavior)
HP:0000742 (Self-mutilation)
HP:0040082 (Happy demeanor)
HP:0000748 (Inappropriate laughter) (reported in 1 family)
Laboratory Abnormalities - Increased succinyladenosine (S-Ado) in serum, urine, and CSF
Increased succinylaminoimidazole carboxamide ribotide (SAICAr)
Decreased S-Ado:SAICAr ratio
Adenylosuccinase deficiency
Miscellaneous - HP:0003593 (Onset in infancy)
HP:0003812 (Variable phenotype), ranging from neonatal HP:0004319 (nonprogressive encephalopathy) to mild HP:0001249 (Intellectual disability) with HP:0000729 (autistic behaviour)
The lower the S-Ado:SAICAr ratio, the more severe the phenotype
Increased succinyladenosine (S-Ado) (P, C, U)
Increased succinylaminoimidazole carboxamide ribotide (SAICAr) (U)
Decreased S-Ado:SAICAr ratio
AFG3L2 604581 SPASTIC ATAXIA 5, AUTOSOMAL RECESSIVE; SPAX5 #614487    2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes HP:0000657 (Oculomotor apraxia)
HP:0000508 (Ptosis)
Abdomen Gastrointestinal HP:0002015 (Dysphagia)
Muscle, Soft Tissue - Distal HP:0003202 (Muscle atrophy), affecting the lower limbs
HP:0002460 (distal muscle weakness), affecting the lower limbs
Misplaced mitochondria seen on skeletal muscle biopsy
Large lipid droplets
Decreased mtDNA
Neurologic Central Nervous System HP:0001257 (Spasticity)
HP:0002313 (spastic paraparesis)
HP:0001251 (ataxia)
HP:0001336 (myoclonus)
HP:0002123 (Myoclonic seizures)
HP:0002505 (Progressive inability to walk)
Generalized HP:0002069 (Tonic-clonic seizures)
HP:0007325 (generalized dystonia)
HP:0002075 (Dysdiadochokinesis)
HP:0001310 (Dysmetria)
HP:0001260 (Dysarthria)
HP:0100543 (Cognitive impairment), mild (in some patients)
HP:0001272 (Cerebellar atrophy)
Peripheral Nervous System HP:0003477 (Peripheral axonal neuropathy)
Chronic demyelinating/remyelinating process seen on sural nerve biopsy
Miscellaneous - HP:0003593 (Onset in infancy) or early childhood
HP:0003676 (Progressive disorder)
HP:0003828 (Variable severity)
Not all patients have all features
 
AGA 613228 ASPARTYLGLUCOSAMINURIA; AGU 208400   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Head and Neck Head HP:0000248 (Brachycephaly)
HP:0000252 (microcephaly)
Face HP:0000280 (Coarse facies)
HP:0000283 (Broad face)
Eyes Crystal-like HP:0000518 (lens opacities)
Nose HP:0005280 (depressed nasal bridge)
HP:0000463 (Anteverted nostrils)
Mouth HP:0000158 (Macroglossia)
HP:0000154 (Wide mouth)
HP:0012471 (Thick lips)
Cardiovascular Heart HP:0001653 (Mitral insufficiency)
Respiratory Lung HP:0002205 (Recurrent respiratory infections)
Abdomen External Features HP:0100790 (Hernias)
Liver HP:0002240 (Hepatomegaly)
Gastrointestinal HP:0002014 (Diarrhea)
Genitourinary External Genitalia (Male) HP:0000053 (Macroorchidism)
Skeletal - HP:0002750 (Delayed bone age)
Mild HP:0000943 (dysostosis multiplex)
Skull HP:0002684 (Thick calvaria)
HP:0002738 (Underdeveloped frontal sinuses)
Spine HP:0002808 (Kyphosis)
HP:0002650 (Scoliosis)
HP:0000926; HP:0004568 Flattening and anterior beaking of vertebral bodies
HP:0003304 (Spondylolysis)
HP:0003302 (Spondylolisthesis)
Limbs HP:0001388 (Joint laxity)
HP:0002756 (Pathologic fractures)
Skin, Nails, Hair Skin HP:0001071 (HP:0001014 (Angiokeratoma) corporis diffusum)
Acne
Neurologic Central Nervous System HP:0000750 (Speech delay)
HP:0001268 (cognitive decline) in childhood
HP:0001249 (Intellectual disability)
HP:0008947 (Hypotonia, early)
HP:0001257 (Spasticity)
HP:0002283 (global brain atrophy)
Seizures (adult)
Voice - HP:0001609 (Hoarse voice)
Hematology - HP:0001922 (Vacuolated lymphocytes)
HP:0001875 (Neutropenia)
Immunology - HP:0002783 (Recurrent infections)
Laboratory Abnormalities - Aspartylglucosaminuria
Little to absent aspartylglucosaminuria activity
Decreased prothrombin time
Miscellaneous - Increased frequency in the Finnish population
98% of Finnish cases due to one mutation
Carrier frequency in Finland 1/40
Onset of symptoms 2-6 years of age
Aspartylglucosaminuria
AIFM1 300169 COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 6; COXPD6 300816   2 Inheritance - HP:0001419 (X-linked recessive)
Respiratory - HP:0002093 (Respiratory insufficiency) due to HP:0003324 (Muscle weakness)
Muscle, Soft Tissue - HP:0003324 (Muscle weakness)
HP:0003202 (Muscle atrophy)
Mitochondrial DNA depletion (20 to 35% of normal) seen on skeletal muscle biopsy
Decreased activity of multiple mitochondrial respiratory complex enzymes
HP:0003200 (Ragged-red fibers)
Increased fatty and connective tissue in skeletal muscle
Neurologic Central Nervous SystemHP:0002376 (Psychomotor regression) (onset within first year of life)
HP:0001263 (global developmental delay), severe
HP:0008947 (Hypotonia, early)
HP:0002375 (Hypokinesia)
HP:0002375 (Involuntary movements)
HP:0002380 (Fasciculations)
HP:0002445 (Tetraplegia)
Seizures
HP:0001265 (Hyporeflexia) or HP:0001284 (Areflexia)
Brain MRI shows HP:0012751 (signal abnormalities in the basal ganglia)
Peripheral Nervous System HP:0009830 (peripheral polyneuropathy)
Laboratory Abnormalities - HP:0002490; HP:0002151 (Increased lactate in serum and CSF)
Increased pyruvate in serum and CSF
Miscellaneous - Onset in first year of life
HP:0003676 (Progressive disorder)
Increased lactate (P, C)
Increased pyruvate (P, C)
AIMP1 603605 LEUKODYSTROPHY, HYPOMYELINATING, 3; HLD3 #260600   5 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0000280 (Coarse facies)
Eyes Horizontal or rotary HP:0000639 (Nystagmus)
Pale fundi
Slow pupillary reflexes
HP:0000505 (visual impairment)
Skeletal - Joint HP:0004576 (large joint contractures), progressive
Spine HP:0002751 (kyphoscoliosis)
Muscle, Soft Tissue - Atrophy of the lower limbs
Neurologic Central Nervous System Global HP:0012758 (neurodevelopmental delay), severe
No speech acquisition
Axial HP:0008947 (Hypotonia, early)
HP:0002313 (spastic paraparesis)
HP:0007256 (Pyramidal tract signs)
Seizures (variable)
Abnormal EEG
Brain MRI shows arrest in myelination
Decreased N-acetylaspartate
HP:0002283 (global brain atrophy)
HP:0007371 (Atrophy of the corpus callosum)
Miscellaneous - Onset in first months of life
HP:0003676 (Progressive disorder)
HP:0000639 (Nystagmus) is often the presenting sign
 
AIMP2 600859 Epilepsy   26795593 2 0  
AKT1 164730 PROTEUS SYNDROME 176920 25451314 2 Inheritance - HP:0001428 (Somatic mutation)
Growth Other HP:0001528 (Hemihypertrophy)
Generalized, unilateral or localized disproportionate HP:0001548 (overgrowth) of any tissue
Head and Neck Head HP:0000256 (Macrocephaly)
HP:0100774 (Hyperostosis) of calvaria, facial bones, and mandible
HP:0000268 (Dolichocephaly)
FaceHP:0000276 (Long face)
Eyes HP:0001140 (Epibulbar dermoids)
HP:0000494 (Downslanting palpebral fissures)
HP:0000508 (Ptosis)
Nose HP:0005280 (depressed nasal bridge)
Wide or HP:0000463 (Anteverted nostrils)
Mouth HP:0000194 (Open mouth)
Cardiovascular Vascular Capillary malformations
HP:0012721 (Venous malformations)
Lymphatic malformations
HP:0002625 (Deep venous thrombosis)
Respiratory Lung Lung cysts
Abdomen Spleen HP:0001744 (Splenomegaly)
Skeletal Spine Megaspondylodysplasia
HP:0002751 (kyphoscoliosis)
Spinal stenosis from angular HP:0002751 (kyphoscoliosis)
Limbs Overgrown long bones
Thin cortices
Skin, Nails, Hair Skin Cerebriform connective tissue nevus
HP:0100764 (Lymphangioma)
HP:0012032 (Lipoma)
Lipohypoplasia
Epidermal nevi
Hypertrophy of skin of soles
Depigmentation/HP:0000953 (hyperpigmentation)
HP:0001028 (Hemangioma), especially thorax and upper abdomen
Skin Histology Highly collagenized connective tissue
HP:0000956 (Acanthosis)
HP:0007543 (epidermal hyperkeratosis)
HP:0007510 (Focal dermal hypoplasia)
Neurologic Central Nervous System Brain malformations
Spinal cord compression by tumor infiltration
HP:0001249 (Intellectual disability), moderate (in some patients)
Neoplasia - Ovarian cystadenoma
Parotid monomorphic adenoma
Miscellaneous - HP:0003593 (Onset in infancy)
HP:0003745 (sporadic) occurrence
Mosaic distribution of lesions
HP:0003676 (Progressive disorder)
 
AKT2 164731 HYPOINSULINEMIC HYPOGLYCEMIA WITH HEMIHYPERTROPHY; HIHGHH #240900   3 Inheritance - HP:0000006 (Autosomal dominant)
Growth Other Macrosomia, neonatal
HP:0001528 (Hemihypertrophy), left-sided
Head and Neck Face Left-sided HP:0001528 (Hemihypertrophy) of face
Chest Breasts HP:0000771 (Gynecomastia)
Abdomen External Features Truncal HP:0001513 (Obesity)
Neurologic Central Nervous System Reduced consciousness, HP:0001943 (Hypoglycemia)-related
HP:0002173 (Hypoglycemic seizures)
Metabolic Features - Hypoinsulinemic HP:0001943 (Hypoglycemia)
Laboratory Abnormalities - Low serum levels of ketone bodies
Low serum levels of branched-chain amino acids
No elevation of free fatty acids
 
AKT3 611223 MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME 2; MPPH2 615937   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Head HP:0000256 (Macrocephaly)
Cardiovascular Vascular Vascular malformations (in some patients)
Skeletal Hands HP:0001162 (Postaxial hand polydactyly)
HP:0001830 (Postaxial feet polydactyly)
Skin, Nails, Hair Skin HP:0000974 (Hyperextensible skin)
Connective tissue dysplasia
HP:0000965 (Cutis marmorata)
Neurologic Central Nervous System HP:0001249 (Intellectual disability)
HP:0000238 (Hydrocephalus)
HP:0002119 (ventriculomegaly)
HP:0007206 (Hemimegalencephaly)
Seizures (in some patients)
HP:0002126 (Polymicrogyria)
HP:0002079 (Thin corpus callosum)
Most cases result from de novo mutations
 
ALAD 125270 PORPHYRIA, ACUTE HEPATIC 612740   3 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Respiratory Lung HP:0002203 (Respiratory paralysis)
Abdomen Gastrointestinal HP:0002013 (Vomiting)
Abdominal colic
Muscle, Soft Tissue - HP:0008947 (Hypotonia)
Muscle HP:0003324 (Muscle weakness)
Neurologic HP:0007141 (Sensorimotor neuropathy)
HP:0003401 (Paresthesia)
Paralysis
Hematology - Hemolytic HP:0001903 (Anemia)
Porphyria
Laboratory Abnormalities - Erythrocyte delta-aminolevulinate dehydratase (ALAD) deficiency
Elevated urinary delta-aminolevulinic acid and porphyrins
Miscellaneous - Very rare
Asymptomatic heterozygotes susceptible to lead toxicity
Exacerbation following stress, decreased food intake, or alcohol use
Hemolytic anemia
Elevated urinary delta-aminolevulinic acid and porphyrins
ALDH18A1 138250 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIIA; ARCL3A 219150   2 Inheritance - HP:0000007 (Autosomal recessive)
HP:0003745 (Isolated cases)
Growth Other HP:0001511 (Intrauterine growth retardation) (IUGR)
HP:0001508 (Failure to thrive)
HP:0001510 (Growth delay)
Head and Neck Head HP:0000248 (Brachycephaly)
HP:0011220 (Prominent forehead)
HP:0000239 (Large fontanels)
Face HP:0005328 (Progeroid appearance)
Ears HP:0000369 (Low-set ears)
HP:0000400 (macrotia)
(HP:0007957 (Corneal opacity)
HP:0000518 (Cataracts)
HP:0000601 (Hypotelorism)
HP:0000316 (Hypertelorism)
HP:0000486 (Strabismus)
HP:0000545 (Myopia)
HP:0007814 (Salt and pepper retinopathy) (in some patients)
Nose HP:0000418 (Pinched nose)
HP:0000430 (Hypoplastic nasal alae)
Mouth HP:0000160 (Small mouth)
Chest External Features HP:0000767 (HP:0000766 (Pectus deformities) excavatum)
Abdomen External Features
HP:0000023 (Inguinal hernia)
HP:0001537 (Umbilical hernia)
Genitourinary Internal Genitalia (Male)
HP:0000028 (Cryptorchidism) (in some patients)
Skeletal - HP:0002750 (Delayed bone age)
HP:0001382 (Hyperextensible joints)
HP:0001373 (joint dislocations)
Skull HP:0002645 (Wormian bones)
HP:0010537 (Wide cranial sutures)
Spine HP:0002650 (Scoliosis)
Pelvis congenital HP:0002827 (Hip dislocations)
Hands HP:0001181 (Adducted thumbs)
Clenched fists
Feet HP:0001762 ( Pes equinovarus)
HP:0001848 (Pes calcaneovalgus)
Skin, Nails, Hair Skin HP:0000973 (Cutis laxa)
Thin, HP:0010648 (translucent skin)
Prominent superficial blood vessels due to HP:0000963 (Thin skin)
Skin Histology Reduced number of elastic fibers
Thin or fragmented elastic fibers
Degenerated elastic fibers
Hair HP:0008070 (Sparse hair)
Muscle, Soft Tissue -
Abnormal fat pad, buttocks and upper thighs (in some patients)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
HP:0008947 (Hypotonia, early)
HP:0002305 (Athetosis)
HP:0001347 (Hyperreflexia)
Seizures
HP:0000273 (Grimacing)
0
ALDH3A2 609523 SJOGREN-LARSSON SYNDROME; SLS 270200   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Head and Neck Eyes Glistening white dots in fundus
HP:0000608 (Macular degeneration)
Superficial HP:0007957 (Corneal opacity)
HP:0000613 (Photophobia)
Teeth HP:0006297 (Enamel hypoplasia)
Skeletal Spine Thoracic HP:0002808 (Kyphosis)
Hands Palm thickening
Feet Sole thickening
Skin, Nails, Hair Skin Pruritic HP:0008064 (ichthyosis) (onset birth to first several months)
Nails Normal nails
Hair Normal hair
Neurologic Central Nervous System HP:0001257 (Spasticity)
HP:0001249 (Intellectual disability)
Seizures
HP:0007305 (CNS demyelination) in central white matter
Laboratory Abnormalities - Fatty alcohol:NAD+ oxidoreductase deficiency in leukocytes and fibroblasts
Miscellaneous - Onset of neurologic symptoms often by 30 months
Prevalent in Sweden
Fatty alcohol:NAD+ oxidoreductase deficiency in leukocytes and fibroblasts
ALDH4A1 606811 HYPERPROLINEMIA, TYPE II; HYRPRO2 #239510   2 Inheritance - HP:0000007 (Autosomal recessive)
Neurologic Central Nervous System Recurrent seizures
HP:0001249 (Intellectual disability)

Laboratory Abnormalities - Hyperprolinemia (10-15 times normal)
Delta-1-pyrroline-5-carboxylate (P5C) levels increased in plasma
P5C levels increased in urine
Delta-1-pyrroline-3-hydroxy-5-carboxylate levels increased in urine
HP:0003355 (Aminoaciduria)
Prolinuria
Hydroxyprolinuria
Glycinuria
Delta-1-pyrroline-5-carboxylate dehydrogenase activity decreased in fibroblasts or leukocytes
Increased prolin (P)
Increased delta-1-pyrroline-5-carboxylate (P5C) (U, P)
Increased delta-1-pyrroline-3-hydroxy-5-carboxylate (U)
Aminoaciduria
Prolinuria
Hydroxyprolinuria
Glycinuria
ALDH5A1 610045 SUCCINIC SEMIALDEHYDE DEHYDROGENASE DEFICIENCY; SSADHD 271980   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes HP:0000496 (Oculomotor abnormalities)

Neurologic Central Nervous System HP:0001263 (global developmental delay), ranging from mild to severe
HP:0001263 (global developmental delay)
Approximately 30% of patients show normal early development
HP:0001270 (Delayed motor development)
HP:0000750 (language delay)
HP:0001249 (Intellectual disability)
HP:0008947 (Hypotonia, early)
HP:0002487 (Hyperkinesis)
HP:0001251 (ataxia)
Seizures
HP:0002121 (Absence seizures)
HP:0002123 (Myoclonic seizures)
Generalized HP:0002069 (Tonic-clonic seizures)
HP:0002133 (Status epilepticus)
EEG abnormalities
HP:0001265 (Hyporeflexia)
MRI shows increased T2-weighted signals in the globus pallidi
Behavioral Psychiatric Manifestations HP:0000717 (Autism), mild
HP:0000752 (Hyperactivity)
HP:0000709 (Psychosis) in older patients
HP:0000718 (aggressive behavior)
HP:0000739 (Anxiety)
HP:0000738 (Hallucinations)
HP:0100716 (Self-injurious behavior)

Laboratory Abnormalities - Increased urinary excretion of 4-hydroxybutyric acid (GHB)
Increased CSF and plasma GHB
Increased urinary excretion of gamma-aminobutyric acid (GABA)
Increased CSF and plasma GABA
Decreased activity of succinic semialdehyde dehydrogenase (SSADH, ALDH5A1), less than 5% of control values
Miscellaneous - HP:0003593 (Onset in infancy) or early childhood
HP:0003812 (Variable phenotype)
Increased 4-hydroxybutyric acid (U, P, C)
Increased gamma-aminobutyric acid (U, P, C)
ALDH7A1 107323 EPILEPSY, PYRIDOXINE-DEPENDENT; EPD 266100   1 Inheritance - HP:0000007 (Autosomal recessive)
Respiratory - HP:0002098 (Respiratory distress), neonatal

Neurologic Central Nervous System Seizures
HP:0002069 (Generalized tonic clonic seizures)
HP:0002123 (Myoclonic seizures)
HP:0002133 (Status epilepticus)
HP:0008947 (Hypotonia, early)
HP:0001263 (Delayed psychomotor development) (mild to severe)
HP:0000750 (Speech delay)
HP:0001249 (Intellectual disability)

Prenatal Manifestations - Fetal distress
Movement HP:0001557 (Abnormal intrauterine movements)

Laboratory Abnormalities - Increased serum and cerebrospinal fluid levels of pipecolic acid
Increased serum, cerebrospinal fluid, and urinary levels of alpha-aminoadipic semialdehyde
Miscellaneous - Prenatal or neonatal onset
Seizures are responsive to pyridoxine treatment
Incidence of 1 in 276,000 in the Netherlands
Increased pipecolic acid (U, P, C)
Increased alpha-aminoadipic semialdehyde (P, U, C)
ALDOB 612724 FRUCTOSE INTOLERANCE, HEREDITARY 229600   3 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Teeth Absent HP:0000670 (Dental caries)
Abdomen Liver HP:0002240 (Hepatomegaly)
HP:0001397 (Liver steatosis)
HP:0001394 (liver cirrhosis)
Gastrointestinal Aversion to sweets and fruit
HP:0002013 (Vomiting)
HP:0002018 (Nausea)
HP:0004395 (Malnutrition)
HP:0002027 (Abdominal pain)
Genitourinary Kidneys HP:0000114 (Proximal tubulopathy)
Skin, Nails, Hair Skin HP:0000952 (Jaundice)
Neurologic Central Nervous System HP:0001254 (Lethargy)
Seizures
Coma
HP:0001249 (Intellectual disability) (if untreated)
Metabolic Features - HP:0001942 (metabolic acidosis)
HP:0003128 (Lactic acidosis)
Laboratory Abnormalities - HP:0001943 (Hypoglycemia)
Fructosemia
HP:0002149 (Hyperuricemia)
HP:0002148 (Hypophosphatemia)
HP:0002910 (HP:0002910 (abnormal liver enzymes) tests)
Fructose-1,6-bisphosphate aldolase B deficiency
Miscellaneous - HP:0003593 (Onset in infancy) after weaning
Symptoms can be prevented by strict dietary restriction
Persistent exposure to fructose leads to chronic liver and kidney complications
Some patients with heterozygous mutations may be symptomatic
Hypoglycemia
Fructosemia
ALG1 605907 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ik; CDG1K #608540   1 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001511 (Intrauterine growth retardation)
Head and Neck Head HP:0000239 (Large fontanels)
HP:0000252 (microcephaly)
Face HP:0000347 (Micrognathia)
Eyes HP:0000572 (Visual loss) (in some)
Abnormal VEP
HP:0000316 (Hypertelorism)
Nose Small, turned-up nose
Mouth HP:0000233 (Thin lips)
Cardiovascular Heart HP:0001638 (Cardiomyopathy) (variable)
Abdomen Liver HP:0002240 (Hepatomegaly) (variable)
Spleen HP:0001744 (Splenomegaly) (variable)
Genitourinary External Genitalia (Male) HP:0000815 (Hypogonadism)
Skeletal - HP:0004576 (large joint contractures)
Neurologic Central Nervous System HP:0001263 (global developmental delay), severe
HP:0001284 (Areflexia)
HP:0008947 (Hypotonia, early)
Seizures, recurrent, refractory
Multifocal epileptic activity
HP:0002283 (global brain atrophy)
Prenatal Manifestations Amniotic Fluid HP:0001789 (Hydrops fetalis), nonimmune
Laboratory Abnormalities - Isoelectric focusing of serum transferrin consistent with CDG type I
Severely decreased activity of beta-1,4-mannosyltransferase (less than 10% of normal)
Miscellaneous - Severe phenotype
Death may occur in early infancy
HP:0001999 (Dysmorphic features) are variable
Isoelectric focusing of serum transferrin (type I)
ALG11 613666 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ip; CDG1P #613661   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly) (rare)
Face HP:0000348 (High forehead) (rare)
Ears HP:0000407 (Sensorineural hearing loss) (rare)
Eyes Delayed pupillary responses (in some patients)
Lack of blink reflex (in some patients)
Poor response to light (in some patients)
HP:0000486 (Strabismus)

Chest Breasts HP:0003186 (Inverted nipples) (rare)

Abdomen Gastrointestinal HP:0011968 (feeding difficulties)
Recurrent HP:0002013 (Vomiting)

Skin, Nails, Hair Hair Low hairline (rare)

Neurologic Central Nervous System HP:0001263 (global developmental delay), severe
HP:0001344 (absent speech)
HP:0000735 (Impaired social interactions)
HP:0008947 (Hypotonia, early), neonatal
Seizures
Peripheral HP:0001276 (Muscle hypertonia)
HP:0002179 (Opisthotonus)

Metabolic Features - HP:0005968 (Body temperature instability)
Laboratory Abnormalities - Abnormal isoelectric focusing of serum transferrin (type 1 pattern)
Increased di- and asialo-transferrin
Decreased tetrasialo-transferrin
Accumulation of shortened dolichol-linked oligosaccharides in patient fibroblasts
Miscellaneous - Onset in first year of life
Isoelectric focusing of serum transferrin (type I)
ALG12 607144 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ig; CDG1G 607143   2 0 Isoelectric focusing of serum transferrin (type I)
ALG13 300776 EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 36; EIEE36 #300884   1 Inheritance - HP:0001419 (X-linked recessive)
Head and Neck Head HP:0000252 (microcephaly) (in 1 patient)
Face HP:0001999 (Dysmorphic facial features) (in 1 patient)
Eyes HP:0000648 (optic atrophy) (in 1 patient)
Horizontal HP:0000639 (Nystagmus) (in 1 patient)
Swelling of the eyelids (in 1 patient)
Abdomen Liver HP:0002240 (Hepatomegaly) (in 1 patient)
Skeletal - Joint HP:0004576 (large joint contractures) (in 1 patient)
Muscle, Soft Tissue - Swelling of the hands and feet (in 1 patient)
Neurologic Central Nervous System Seizures, refractory
HP:0001263 (Delayed psychomotor development)
HP:0002376 (Psychomotor regression) after onset of seizures
EEG shows HP:0002521 (hypsarrhythmia)
HP:0008947 (Hypotonia, early)
HP:0000238 (Hydrocephalus) (in 1 patient)
HP:0007256 (Pyramidal tract signs) (in 1 patient)
HP:0002071 (extrapyramidal signs) (in 1 patient)
Hematology - Increased bleeding tendency (in 1 patient)
Prolonged APPT (in 1 patient)
Immunology - HP:0002783 (Recurrent infections) (in 1 patient)
Laboratory Abnormalities - Abnormal isoelectric focusing of serum transferrin (type 1 pattern) (in 1 patient)
Miscellaneous - HP:0003593 (Onset in infancy)
Isoelectric focusing of serum transferrin (type I)
ALG2 607905 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ii; CDG1I #607906   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes HP:0000589 (coloboma)
HP:0000518 (Cataracts)
HP:0000505 (Visual impairment)
HP:0000639 (Nystagmus)
Abdomen Liver HP:0002240 (Hepatomegaly)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development), severe
HP:0001249 (Intellectual disability)
Seizures
HP:0002521 (hypsarrhythmia)
HP:0001347 (Hyperreflexia)
Delayed cerebral myelination
Decreased white matter
Hematology - HP:0001928 (Coagulation abnormalities)
Laboratory Abnormalities - Increased di- and asialo-transferrin characteristic of type 1 pattern
Miscellaneous - Onset in early infancy
Isoelectric focusing of serum transferrin (type I)
ALG3 608750 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Id; CDG1D #601110    2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000252 (microcephaly)
Ears HP:0000400 (macrotia)
Eyes HP:0000648 (optic atrophy)
Iris HP:0000589 (coloboma)
Severe HP:0000505 (Visual impairment)
Electroretinography (ERG) shows decreased amplitudes
HP:0000286 (Epicanthus)
HP:0000486 (Strabismus)
Nose HP:0000431 (Broad nasal bridge)
HP:0000414 (Bulbous nose)
Mouth HP:0000193 (Bifid uvula)
HP:0000218 (High-arched palate)
Abdomen Gastrointestinal HP:0002013 (Vomiting)
HP:0002014 (Diarrhea)
Food intolerance
Duodenal villous atrophy
Skeletal - HP:0002804 (HP:0002804 (Arthrogryposis) multiplex)
Limbs HP:0004576 (large joint contractures)
Hands HP:0001181 (Adducted thumbs)
HP:0004576 (large joint contractures) of the hands
HP:0004209 (Fifth finger clinodactyly)
HP:0100807 (Long fingers)
Feet HP:0001762 ( Pes equinovarus)
Skin, Nails, Hair Nails Small, HP:0002164 (dysplastic nails)
Neurologic Central Nervous System HP:0001263 (global developmental delay)
HP:0002521 (hypsarrhythmia)
HP:0001272 (Cerebellar atrophy)
HP:0002283 (global brain atrophy)
Seizures
Axial HP:0008947 (Hypotonia, early)
HP:0001347 (Hyperreflexia)
Laboratory Abnormalities - Abnormal isoelectric focusing of serum transferrin (type 1 pattern without increase of asialotransferrin)
Hypoglycosylation of plasma glycoproteins
Dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase deficiency
Isoelectric focusing of serum transferrin (type I)
ALG6 604566 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ic; CDG1C #603147   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes HP:0000486 (Strabismus)
Neurologic Central Nervous System Axial HP:0008947 (Hypotonia, early)
HP:0001263 (global developmental delay)
HP:0001284 (Areflexia)
Seizures
HP:0001251 (ataxia)
Hematology - Factor XI deficiency
Laboratory Abnormalities - HP:0002910 (abnormal liver enzymes) during infections
Abnormal isoelectric focusing of serum transferrin (type 1 pattern)
Dolichyl-P-Glc:Man(9)GlcNAc(2)-PP-dolichyl glucosyltransferase deficiency
Decreased serum cholesterol
Decreased factor XI
Decreased antithrombin III
Decreased protein C
Isoelectric focusing of serum transferrin (type I)
ALG9 606941 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Il; CDG1L 608776   2 0 Isoelectric focusing of serum transferrin (type I)
ALMS1 606844 ALSTROM SYNDROME; ALMS   23188138 2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Weight Truncal HP:0001513 (Obesity) (onset in childhood)
Head and Neck Ears HP:0000408 (Hearing loss, progressive sensorineural)
HP:0000388 (Otitis media)
Eyes HP:0000548 (Cone-rod dystrophy)
HP:0000580 (Pigmentary retinopathy)
HP:0000613 (Photophobia) (infancy)
HP:0000639 (Nystagmus) (infancy)
HP:0000618 (Blindness)
Subcapsular HP:0000518 (Cataracts)
Teeth HP:0000230 (Gingivitis)
Discolored enamel
Cardiovascular Heart HP:0001644 (dilated cardiomyopathy) (infancy)
HP:0001635 (Congestive heart failure)
Vascular Atherosclerosis
HP:0000822 (Hypertension)
Respiratory Airways Asthma
HP:0006532 (Recurrent pulmonary infections)
Chest Breasts HP:0000771 (Gynecomastia)
Abdomen Liver HP:0012115 (Hepatitis), chronic active
HP:0002240 (Hepatomegaly)
HP:0001397 (Liver steatosis)
Genitourinary Kidneys Nephritis, chronic
HP:0000083 (Renal failure)
HP:0012210 (Renal structural anomalies)
Narrowing of the ureteropelvic junctions
Deformities of the calyceal system
Skeletal - HP:0005616 (Advanced bone age)
Skull HP:0100774 (Hyperostosis) frontalis interna
Spine HP:0002808 (Kyphosis)
HP:0002650 (Scoliosis)
Hands
Feet HP:0001763 (pes planus)
Skin, Nails, Hair Skin HP:0000956 (Acanthosis) nigricans
Hair HP:0001596 (Alopecia)
Neurologic - HP:0012758 (neurodevelopmental delay)
Endocrine Features - Menstrual irregularities
HP:0000831 (Insulin resistant diabetes)
Hypergonadotropic HP:0000815 (Hypogonadism) (males)
HP:0000873 (Diabetes insipidus)
HP:0000821 (Hypothyroidism)
Multinodular goiter
HP:0000824 (Growth hormone deficiency)
Laboratory Abnormalities - HP:0000842 (Hyperinsulinemia)
HP:0002149 (Hyperuricemia)
HP:0002155 (Hypertriglyceridemia)
Low HDL-cholesterol
Normal total cholesterol
HP:0002910 (abnormal liver enzymes)
 
ALPL 171760 HYPOPHOSPHATASIA, INFANTILE 241500   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0008873 (Short limb short stature)
Other HP:0001508 (Failure to thrive)
Head and Neck Eyes HP:0000592 (Blue sclerae)
Teeth Poorly formed teeth
Respiratory - HP:0002205 (Recurrent respiratory infections)
HP:0002104 (Apnea)
Chest Ribs, Sternum, Clavicles and Scapulae HP:0000773 (Short ribs)
HP:0000897 (Rachitic rosary)
Rib fractures
Small thoracic cage
Clavicles least affected bone
Abdomen Gastrointestinal HP:0002039 (Anorexia)
HP:0002013 (Vomiting)
HP:0002019 (Constipation)
Genitourinary Kidneys HP:0000121 (Nephrocalcinosis)
Skeletal - Lack of ossification
Fractures
Marked retardation of infantile form
Skull Poorly mineralized cranium
HP:0010537 (Wide cranial sutures)
HP:0011324 (multisutural craniosynostosis) in infantile form
Poorly mineralized cranium
Spine Vertebral bodies often unossified
HP:0008428 (Vertebral clefts)
HP:0000926 (Platyspondyly)
Limbs HP:0002983 (Micromelia)
Osteogenesis defect
Bowed, short lower extremities
'Spurs' in midshaft of ulna and fibula
HP:0003021 (Metaphyseal cupping)
Skin, Nails, Hair Skin Skin dimple over apex of long bone angulation
Neurologic Central Nervous System Seizures
HP:0008947 (Hypotonia, early)
HP:0000737 (Irritability)
HP:0002170 (Intracranial hemorrhage)
Voice - HP:0001620 (High pitched voice)
Hematology - Myelophthisic HP:0001903 (Anemia)
Prenatal Manifestations Amniotic Fluid HP:0001561 (Polyhydramnios)
Delivery Stillborn or infantile death usual in prenatal form
Laboratory Abnormalities - HP:0003072 (Hypercalcemia)
HP:0002150 (Hypercalciuria)
Phosphoethanolaminuria
Elevated plasma and urine inorganic pyrophosphate (PPi)
Decreased tissue and serum alkaline phosphatase
Elevated serum phosphate in heterozygotes
Low serum alkaline phosphatase in heterozygotes
Mildly elevated phosphoethanolamine urinary excretion in heterozygotes
Miscellaneous - Four separate types - (1) severe perinatal ('lethal') form, (2) severe infantile form, (3) childhood form, and (4) adult form
Stillborn or infantile death usual in prenatal form
Death frequent in severe infantile form
Severe infantile form presents before 6 months
HP:0001954 (Episodic fever)
Phosphoethanolaminuria
Increased inorganic pyrophosphate (P, U)
Decreased alkaline phosphatase (P)
AMACR 604489 ALPHA-METHYLACYL-CoA RACEMASE DEFICIENCY; AMACRD #614307   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes HP:0000580 (Pigmentary retinopathy) (variable)
HP:0000505 (Visual impairment)
Neurologic Central Nervous System Seizures
HP:0002133 (Status epilepticus)
HP:0001257 (Spasticity)
HP:0002322 (Resting tremor)
HP:0002076 (Migraine)
cerebellar HP:0001251 (ataxia)
Cerebellar HP:0001260 (Dysarthria)
White matter hyperintensities in various brain regions
Peripheral Nervous System HP:0007141 (Sensorimotor neuropathy)
Behavioral Psychiatric Manifestations HP:0000716 (Depression)
Endocrine Features - Primary HP:0000815 (Hypogonadism) (in 2 male patients)
Laboratory Abnormalities - Increased serum pristanic acid
Normal or increased serum phytanic acid
Increased serum C26-bile-acid intermediates
Miscellaneous - Onset usually in second decade
HP:0003812 (Variable phenotype)
HP:0006846 (Acute encephalopathy) may occur
Increased pristanic acid (P)
Normal or increased phytanic acid (P)
Increased C26-bile-acid intermediates (P)
AMER1 300647 OSTEOPATHIA STRIATA WITH CRANIAL SCLEROSIS; OSCS 300373   2 Inheritance - HP:0001423 (X-linked dominant)
Growth Height HP:0004322 (short stature) (in males)
Other HP:0001508 (Failure to thrive) (in males)
Head and Neck Head HP:0000256 (Macrocephaly)
HP:0000239 (Large fontanels)
HP:0010537 (Wide cranial sutures)
HP:0001476 (Delayed closure of anterior fontanelle)
Face HP:0002007 (Frontal bossing)
HP:0000341 (Bitemporal narrowing)
HP:0000347 (Micrognathia)
HP:0010628 (Facial palsy)
Ears HP:0000369 (Low-set ears)
HP:0000358 (Posteriorly rotated ears)
HP:0008551 (Small ears)
HP:0000396 (Overfolded ears)
HP:0000405 (Conductive hearing loss)
Eyes HP:0000316 (Hypertelorism)
HP:0000286 (Epicanthus)
Nose HP:0007965 (Broad nasal bridge)
Mouth HP:0000175 (Cleft palate)
HP:0100333 (Unilateral cleft lip)
HP:0000193 (Bifid uvula)
HP:0000201 (Pierre Robin sequence) (in males)
HP:0012471 (Thick lips) (in males)
HP:0000218 (High-arched palate) (15%)
Teeth HP:0000695 (Neonatal teeth)
HP:0000689 (Dental malocclusion)
HP:0000678 (Crowded teeth)
Neck HP:0000465 (Webbed neck)
Cardiovascular Heart HP:0001629 (Ventricular septal defect)
HP:0001631 (Atrial septal defect)
Vascular HP:0001643 (Patent ductus arteriosus)
Respiratory - HP:0002104 (Apnea)
Nasopharynx Paranasal HP:0006784 (paranasal sinus hypoplasia)
HP:0002779 (Tracheomalacia)
Larynx HP:0005950 (Laryngeal web)
Chest Ribs, Sternum, Clavicles and Scapulae HP:0000885 (Broad ribs)
HP:0000767 (HP:0000766 (Pectus deformities) excavatum)
Long, straight clavicles
Broad medial and lateral clavicles
Breasts HP:0006610 (Widely spaced nipples)
Abdomen External Features HP:0001539 (Omphalocele) (rare, in males)
Gastrointestinal Intestinal HP:0002566 (Malrotation) (rare, in males)
HP:0002025 (Anal stenosis) (rare, in males)
HP:0002023 (Anal atresia) (rare, in males)
HP:0002020 (Gastroesophageal reflux)
Genitourinary KidneysHP:0000003 (Multicystic kidney) (rare, in males)
Nephrogenic rests (rare, in males)
Skeletal - HP:0010740 (Osteopathia striata) (linear striations of long bone diametaphyses, only in females)
Increased trabecular thickness seen on iliac bone biopsy
Joint HP:0004576 (large joint contractures)
Skull Sclerotic cranial base
Sclerotic mastoids (31%)
Occipital bossing
Cranial sclerosis
HP:0002684 (Thick calvaria)
Trapezoidal shaped skull
Spine HP:0005619 (Thoracolumbar gibbus)
HP:0002650 (Scoliosis) (23%)
HP:0002414 (Spina bifida) occulta
Limbs HP:0002990 (Absent fibulae)
Short fibulae
Hands HP:0004209 (Fifth finger clinodactyly)
HP:0001166 (Arachnodactyly)
Finger HP:0004576 (large joint contractures)
HP:0100490 (Camptodactyly)
Duplicate phalanges
Spatulate distal phalanges
Feet HP:0001762 ( Pes equinovarus) (in males)
HP:0005830 (Toe contractures)
Muscle, Soft Tissue - Nemaline HP:0003756 (Myopathy)
Neurologic Central Nervous System HP:0000238 (Hydrocephalus)
Headaches
HP:0000750 (Speech delay) (10%)
Transitional HP:0010628 (Facial palsy) (15%)
HP:0008947 (Hypotonia, early) (in males)
Seizures (rare, in males)
HP:0001249 (Intellectual disability), mild-moderate (28%, usually in males)
Partial HP:0001274 (Agenesis of corpus callosum) (rare, in males)
Voice - HP:0001611 (Nasal speech)
Prenatal Manifestations Amniotic Fluid HP:0001562 (Oligohydramnios)
HP:0001561 (Polyhydramnios)
Miscellaneous - Increased morbidity/mortality in affected males
One-third of cases are HP:0003745 (sporadic)
Onset of linear striations between 5 months and 6 years (only in affected females)
 
AMPD2 102771 PONTOCEREBELLAR HYPOPLASIA, TYPE 9; PCH9 615809   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly), progressive (up to -9 SD)
Eyes HP:0000648 (optic atrophy)
Cortical HP:0000618 (Blindness)
Poor fixation
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development), profound
Absent development
Axial HP:0008947 (Hypotonia, early)
HP:0001257 (Spasticity)
HP:0002169 (Clonus)
HP:0001347 (Hyperreflexia)
Seizures
PontoHP:0001321 (Cerebellar hypoplasia)
HP:0002079 (Thin corpus callosum)
Fluid filled posterior fossa
Cerebral HP:0002120 (Cortical atrophy)
HP:0002119 (ventriculomegaly)
Defective myelination of the deep white matter
Miscellaneous - HP:0003577 (Onset at birth) or early infancy
0
AMT 238310 GLYCINE ENCEPHALOPATHY; GCE #605899   2 Inheritance - HP:0000007 (Autosomal recessive)
Neurologic Central Nervous System HP:0001274 (agenesis of corpus callosum) (variable)
HP:0001254 (Lethargy)
Seizures
HP:0100247 (Hiccups)
HP:0008947 (Hypotonia, early)
HP:0001265 (Hyporeflexia) to HP:0001347 (Hyperreflexia)
HP:0001336 (myoclonus)
HP:0001249 (Intellectual disability)
HP:0010851 (Burst suppression pattern) on neonatal EEG
Expressive speech deficit
Behavioral Psychiatric Manifestations HP:0000752 (Hyperactivity)
HP:0100710 (Impulsivity)
HP:0000718 (aggressive behavior)
HP:0000737 (Irritability)
HP:0000711 (Restlessness)
Laboratory Abnormalities - Hyperglycinemia
Hyperglycinuria
Hepatic glycine cleavage defect
Elevated CSF glycine
Elevated CSF/plasma glycine ratio
Miscellaneous - HP:0001522 (Death in infancy) common for patients with the classic neonatal form
Patients with atypical form have milder disease, with onset in the first months of life and increased survival
Hyperglycinemia
Hyperglycinuria
Elevated CSF glycine
Elevated CSF/plasma glycine ratio
ANK3 600465 MENTAL RETARDATION, AUTOSOMAL RECESSIVE 37; MRT37 615493   2 Inheritance - HP:0000007 (Autosomal recessive)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System HP:0001249 (Intellectual disability), moderate
HP:0001257 (Spasticity)
HP:0008947 (Hypotonia, early)
HP:0002360 (Sleep disturbance)
Seizures (in 1 patient)
Behavioral Psychiatric Manifestations HP:0000718 (Aggressive behavior)
HP:0000752 (Hyperactivity)
HP:0003763 (bruxism)
 
ANKH 605145 CHONDROCALCINOSIS 2; CCAL2 118600 15461680 2 Inheritance - HP:0000006 (Autosomal dominant)
Skeletal Limbs Polyarticular HP:0000934 (Chondrocalcinosis) (cartilage calcification)
Calcium pyrophsophate dihydrate (CPPD) crystal deposition (knee, symphysis pubis, wrist)
PseudoHP:0002758 (Osteoarthritis)
Pseudogout
HP:0003040 (Arthropathy)
HP:0002758 (Osteoarthritis)
Miscellaneous - Age of onset third decade
 
ANKRD11 611192 KBG SYNDROME; KBGS #148050 25543316 2 Inheritance - HP:0000006 (Autosomal dominant)
Growth Height HP:0004322 (short stature) (less than tenth percentile)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0000311 (Round face) early in life
HP:0000325 (Triangular face) later in life
HP:0000343 (Long philtrum)
Ears HP:0000400 (macrotia)
Eyes HP:0000316 (Hypertelorism)
HP:0000506 (telecanthus)
HP:0000637 (Long palpebral fissures)
HP:0011229 (Broad eyebrows)
Nose HP:0000463 (Anteverted nares)
HP:0000430 (Hypoplastic nasal alae) nasi
Teeth HP:0001572 (Macrodontia)
Wide upper central incisors
Ridged teeth
Fused incisors
HP:0000677 (Oligodontia)
Chest Ribs, Sternum, Clavicles and Scapulae Cervical HP:0000902 (rib fusion)
Accessory HP:0000891 (cervical rib)s
Genitourinary Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
Skeletal - HP:0002750 (Delayed bone age)
Spine HP:0002948 (Vertebral body fusion)
HP:0008438 (Vertebral arch abnormalities)
Thoracic HP:0002808 (Kyphosis)
Hands HP:0004209 (Fifth finger clinodactyly)
Decreased hand length
HP:0006101 (Finger syndactyly)
Skin, Nails, Hair Skin HP:0000954 (Single transverse palmar crease)
Hair HP:0011229 (Broad eyebrows)
HP:0000294 (Low anterior hairline)
HP:0002162 (Low posterior hairline)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
HP:0001249 (Intellectual disability)
Miscellaneous - Male to female ratio 21:8
 
ANO3 610110 DYSTONIA 24; DYT24 615034   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Head Head HP:0002322 (Resting tremor) (in some patients)
Face Oromandibular HP:0007325 (generalized dystonia) (in some patients)
Eyes HP:0000643 (Blepharospasm) (in some patients)
Teeth Cervical HP:0007325 (generalized dystonia)
Respiratory Larynx Laryngeal HP:0002322 (Resting tremor)
Skeletal Limbs Dystonic posturing of the upper limb
Neurologic Central Nervous System HP:0007325 (generalized dystonia), focal
HP:0002322 (Resting tremor) of the upper limb
Head HP:0002322 (Resting tremor)
Voice - Voice HP:0002322 (Resting tremor)
Miscellaneous - Average age at onset is 24 years (range 4 to 58 years)
HP:0003829 (Incomplete penetrance)
 
AP1S2 300629 PETTIGREW SYNDROME; PGS #304340   2 Inheritance - HP:0001419 (X-linked recessive)
Head and Neck Face HP:0000280 (Coarse facies)
HP:0000276 (Long face)
HP:0011220 (Prominent forehead)
HP:0000303 (Prominent jaw)
Eyes HP:0000490 (Deep-set eyes)
Nose HP:0000448 (Large nose)
Mouth HP:0000154 (wide mouth)
HP:0012471 (full lips)
Skeletal - Joint HP:0004576 (large joint contractures)
Spine HP:0002650 (Scoliosis)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
HP:0001249 (Intellectual disability), severe
Seizures
HP:0001266 (Choreoathetosis)
HP:0001257 (Spasticity)
HP:0001251 (ataxia)
HP:0000238 (Hydrocephalus) (in some patients)
HP:0002119 (ventriculomegaly) (in some patients)
HP:0001305 (Dandy-Walker malformation) (in some patients)
Iron deposition in the basal ganglia (in some patients)
HP:0002514 (Intracranial calcifications) (in some patients)
Axonal dystrophy (in some patients)
Peripheral Nervous System HP:0001347 (Hyperreflexia)
Behavioral Psychiatric Manifestations HP:0100716 (Self-injurious behavior)
Miscellaneous - HP:0003593 (Onset in infancy)
Additional features are variably present
 
AP4B1 607245 SPASTIC PARAPLEGIA 47, AUTOSOMAL RECESSIVE; SPG47 614066   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature) (1 family)
Head and Neck Head HP:0000252 (microcephaly)
Face
HP:0000280 (Coarse facies)
HP:0008947 (Hypotonia, early) face
HP:0000341 (Bitemporal narrowing)
HP:0000322 (Short philtrum)
Nose
HP:0000431 (Broad nasal bridge)
HP:0000414 (Bulbous nose)
Mouth
Everted upper vermilion
HP:0000154 (Wide mouth)
HP:0000218 (High-arched palate)
Skeletal - HP:0001388 (Joint laxity) (1 family)
Limbs HP:0002816 (Genu recurvatum) (1 family)
Feet HP:0001763 (pes planus) (1 family)
HP:0001762 ( Pes equinovarus) (1 family)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early), neonatal
HP:0001276 (Muscle hypertonia) later
Neurologic Central Nervous System
HP:0001263 (Delayed psychomotor development)
HP:0001249 (Intellectual disability), severe
HP:0001257 (Spasticity)
HP:0001347 (Hyperreflexia)
HP:0002540 (inability to walk) unaided
HP:0002515 (Waddling gait)
HP:0003487 (Extensor plantar responses)
HP:0000750 (language delay)
HP:0001260 (Dysarthria)
Seizures
HP:0007325 (generalized dystonia)
HP:0002079 (Thin corpus callosum)
Periventricular HP:0002500 (White matter abnormalities)
White matter loss
HP:0002119 (ventriculomegaly)
Behavioral Psychiatric Manifestations
Stereotypic laughter
Shy character (1 family)
Miscellaneous - HP:0003577 (Onset at birth)
Slowly progressive
 
AP4E1 607244 SPASTIC PARAPLEGIA 51, AUTOSOMAL RECESSIVE; SPG51 613744   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0000276 (Long face)
HP:0000341 (Bitemporal narrowing)
Prominent HP:0000307 (Pointed chin)
HP:0000322 (Short philtrum)
Facial HP:0008947 (Hypotonia, early)
HP:0000280 (Coarse facies)
Ears Prominent antihelix
Eyes HP:0000494 (Downslanting palpebral fissures)
HP:0000639 (Nystagmus)
Nose HP:0003189 (Large nose)
HP:0000431 (Broad nasal bridge)
HP:0000414 (Bulbous nose)
Mouth HP:0000154 (Wide mouth)
HP:0002307 (Drooling)
Skeletal - Joint HP:0004576 (large joint contractures)
Feet HP:0001762 ( Pes equinovarus)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early), neonatal and later
HP:0003199 (Decreased muscle mass) in the thighs
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
HP:0001249 (Intellectual disability), severe
Spastic HP:0002445 (quadriplegia)
HP:0001347 (Hyperreflexia)
HP:0003487 (Extensor plantar responses)
Seizures
HP:0001344 (absent speech) development
HP:0002120 (Cortical atrophy)
HP:0001272 (Cerebellar atrophy)
HP:0002119 (ventriculomegaly)
Diffuse white matter loss
Behavioral Psychiatric Manifestations Stereotypic laughter
Shy behavior
Amicable behavior
Miscellaneous - HP:0003577 (Onset at birth)
 
AP4M1 602296 SPASTIC PARAPLEGIA 50, AUTOSOMAL RECESSIVE; SPG50 612936   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly)
Face Pseudobulbar signs
HP:0002307 (Drooling)
HP:0001999 (Dysmorphic facial features) (in some patients)
HP:0000280 (Coarse facies)
HP:0000341 (Bitemporal narrowing)
HP:0000322 (Short philtrum)
Hypotonic face
Eyes HP:0000486 (Strabismus)
Nose
HP:0000414 (Bulbous nose)
Broad nasal ridge
Mouth
Everted upper vermilion
HP:0000303 (Prominent jaw) reflex
HP:0000154 (Wide mouth)
HP:0000218 (High-arched palate)
Skeletal Hands HP:0001181 (Adducted thumbs)
Feet HP:0001762 ( Pes equinovarus)
Neurologic Central Nervous System
HP:0001263 (Delayed psychomotor development)
HP:0001249 (Intellectual disability), severe
HP:0002505 (Progressive inability to walk)
Spastic HP:0002445 (quadriplegia)
HP:0001347 (Hyperreflexia)
HP:0003487 (Extensor plantar responses)
HP:0008947 (Hypotonia, early), neonatal
HP:0001276 (Muscle hypertonia)
HP:0001344 (absent speech) development
Seizures
HP:0001272 (Cerebellar atrophy)
HP:0002079 (Thin corpus callosum)
HP:0002119 (ventriculomegaly)
White matter lesions
Decreased myelin
HP:0002171 (Gliosis)
Neuroaxonal abnormalities
Miscellaneous -
HP:0003577 (Onset at birth) or prenatally
 
AP4S1 607243 SPASTIC PARAPLEGIA 52, AUTOSOMAL RECESSIVE; SPG52 #614067   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0000280 (Coarse facies)
Nose HP:0000448 (Large nose)
HP:0000414 (Bulbous nose)
Mouth HP:0000154 (Wide mouth)
Skeletal - Joint HP:0004576 (large joint contractures)
Feet HP:0001762 ( Pes equinovarus)
Muscle, Soft Tissue - HP:0001276 (Muscle hypertonia)
Decreased shank muscle mass
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
HP:0001249 (Intellectual disability), severe
HP:0001257 (Spasticity)
HP:0001347 (Hyperreflexia)
HP:0002505 (Progressive inability to walk)
HP:0003487 (Extensor plantar responses)
HP:0001344 (absent speech) development
Behavioral Psychiatric Manifestations Stereotypic laughter
Shy character
Amicable character
Miscellaneous - HP:0003577 (Onset at birth)
 
APOPT1 616003 MITOCHONDRIAL COMPLEX IV DEFICIENCY 220110   2 Inheritance - HP:0000007 (Autosomal recessive)
Mitochondrial
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Ears HP:0000407 (sensorineural hearing loss)
Eyes HP:0000648 (optic atrophy)
HP:0000580 (Pigmentary retinopathy)
HP:0000508 (Ptosis)
Cardiovascular Heart HP:0001639 (hypertrophic cardiomyopathy)
Respiratory - HP:0002880 (Respiratory difficulties)
HP:0002878 (Respiratory failure) due to HP:0003324 (Muscle weakness)
Exertional HP:0002094 (dyspnea)
Abdomen Liver HP:0001410 (Liver dysfunction)
HP:0002240 (Hepatomegaly)
Liver biopsy shows increased lipid droplets and HP:0012103 (Abnormality of the mitochondrion)
Genitourinary Kidneys HP:0001994 (Renal Fanconi syndrome)
HP:0000124 (Renal tubular dysfunction)
Biopsy shows decreased cytochrome c oxidase
Muscle, Soft Tissue - HP:0003324 (Muscle weakness)
HP:0008947 (Hypotonia, early)
HP:0003546 (Exercise intolerance)
Muscle biopsy shows decrease or absence of cytochrome c oxidase
Increased lipid droplets and HP:0012103 (Abnormality of the mitochondrion)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
HP:0001270 (Delayed motor development)
HP:0008947 (Hypotonia, early)
HP:0001251 (ataxia)
HP:0007256 (pyramidal tract signs)
Seizures
HP:0001249 (Intellectual disability)
HP:0002490 (Increased CSF lactate)
Symmetric lesions in the basal ganglia consistent with Leigh syndrome (256000), in a subset of patients
Metabolic Features - HP:0003128 (Lactic acidosis)
Hematology - HP:0001903 (Anemia) (associated with mutation in the COX10 gene)
Laboratory Abnormalities - HP:0002151 (Increased serum lactate)
HP:0002490 (Increased CSF lactate)
HP:0000093 (Proteinuria)
HP:0003076 (Glucosuria)
HP:0003355 (Aminoaciduria)
HP:0003109 (Hyperphosphaturia)
Decreased activity of cytochrome c oxidase in muscle and fibroblasts
Miscellaneous - Marked clinical heterogeneity
Symptom onset ranges from infancy to adulthood
Death may occur in infancy
Genetic heterogeneity (may be caused by mutation in nuclear-encoded or mitochondrial-encoded genes)
Subset of patients have Leigh syndrome (256000)
Subset of patients have French-Canadian Leigh syndrome (220111)
Increased lactate (P, C)
APP 104760 CEREBRAL AMYLOID ANGIOPATHY, APP-RELATED #605714    2 Inheritance - HP:0000006 (Autosomal dominant)
Cardiovascular Vascular HP:0011970 (Cerebral amyloid angiopathy)
Cerebral artery HP:0011034 (amyloidosis) (amyloid deposition in cerebral arteries)
HP:0002637 (Cerebral ischemia)
Recurrent HP:0001297 (stroke)s
Recurrent HP:0001342; HP:0011695; cerebral and HP:0011695 (Cerebellar hemorrhage)
Microbleeds (less than 5 mm in diameter) occur at the gray-white matter junction in the cerebral hemispheres and cerebellum and do not occur in the thalamus, basal ganglia, or brainstem
Hyaline thickening of cerebral arteries
HP:0004938 (Tortuous cerebral arteries)
Neurologic Central Nervous System HP:0000726 (Dementia), progressive, with onset of disease
Miscellaneous - Onset in middle age (44 to 60 years)
 
APTX 606350 ATAXIA, EARLY-ONSET, WITH OCULOMOTOR APRAXIA AND HYPOALBUMINEMIA; EAOH #208920 15174536 2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes HP:0000657 (Oculomotor apraxia) (in 86% of patients)
HP:0000571 (Hypometric saccades)
Gaze-evoked HP:0000639 (Nystagmus)
ProgressiveExternal HP:0000544 (Ophthalmoplegia)
Skeletal Spine HP:0002650 (Scoliosis)
Feet HP:0001761 (Pes cavus)
Muscle, Soft Tissue - Distal HP:0003202 (Muscle atrophy) due to HP:0009830 (Peripheral neuropathy)
HP:0003324 (Muscle weakness)
Muscle coenzyme Q deficiency
Neurologic Central Nervous System cerebellar HP:0001251 (ataxia), severe
HP:0001251 (ataxia)
HP:0002070 (limb ataxia)
HP:0002078 (Trunk ataxia)
Mosy patients become wheelchair-bound after 10 years
HP:0000657 (Oculomotor apraxia)
HP:0001266 (Choreoathetosis) (in 79%), more frequent at disease onset
HP:0002322 (Resting tremor)
HP:0007325 (generalized dystonia)
HP:0001260 (Dysarthria)
HP:0001268 (cognitive decline) in a subset of patients
HP:0000726 (Dementia) in a subset of patients
HP:0001272 (Cerebellar atrophy)
Peripheral Nervous System Axonal sensory and motor HP:0009830 (Peripheral neuropathy), severe

HP:0001265 (Hyporeflexia)
HP:0001284 (Areflexia)
Nerve biopsy shows axonal degeneration and axonal sprouting
Depletion of large myelinated fibers
Laboratory Abnormalities - HP:0003073 (Hypoalbuminemia) (in 83%)
HP:0003124 (Hypercholesterolemia) (in 75%)
Miscellaneous - Onset is usually in childhood or adolescence (2 to 18 years)
Adult onset has been reported
HP:0000657 (Oculomotor apraxia) is not always present
 
AQP2 107777 DIABETES INSIPIDUS, NEPHROGENIC, AUTOSOMAL 125800   3 Inheritance - HP:0000006 (Autosomal dominant)
HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Other HP:0001508 (Failure to thrive)
Abdomen Gastrointestinal HP:0002013 (Vomiting)
HP:0002019 (Constipation)
HP:0011968 (feeding difficulties)
HP:0001959 (Polydipsia)
Genitourinary Kidneys HP:0000103 (Polyuria)
Bladder Lower urinary tract dilatation may occur over time
Neurologic Central Nervous System Seizures
HP:0001249 (Intellectual disability) can occur in patients with repeated episodes of HP:0001944 (Dehydration)
Behavioral Psychiatric Manifestations HP:0000737 (Irritability)
Metabolic Features - Hypertonic HP:0001944 (Dehydration)
HP:0001954 (Episodic fever)
Laboratory Abnormalities - HP:0003228 (Hypernatremia)
High serum osmolality
Inappropriately low urine osmolality
Normal or increased levels of serum arginine vasopressin (antidiuretic hormone, 192340)
Normal extrarenal responses to dDAVP administration
Increased urinary cyclic AMP (cAMP) in response to dDAVP administration
Miscellaneous - Onset in first weeks of life
Both HP:0000006 (Autosomal dominant) and HP:0000007 (Autosomal recessive) inheritance have been reported
Genetic heterogeneity (see 304800)
 
ARFGEF2 605371 PERIVENTRICULAR HETEROTOPIA WITH MICROCEPHALY, AUTOSOMAL RECESSIVE; ARPHM #608097   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive) (in some patients)
Head and Neck Head HP:0000252 (microcephaly), progressive (-3 to -5 SD)
Eyes HP:0000817 (Poor eye contact)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
HP:0001249 (Intellectual disability), severe
Seizures
HP:0002521 (hypsarrhythmia)
HP:0002273 (Quadriplegia)
Periventricular nodular HP:0002282 (heterotopia) seen on MRI
HP:0002079 (Thin corpus callosum)
Miscellaneous - HP:0003593 (Onset in infancy)
 
ARG1 608313 ARGININEMIA #207800   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001510 (Failure to thrive)
Abdomen External Features HP:0002039 (Anorexia)
HP:0002013 (Vomiting)
Neurologic Central Nervous System Progressive spastic HP:0002445 (quadriplegia)
Seizures
HP:0012758 (neurodevelopmental delay)
HP:0001249 (Intellectual disability)
Behavioral Psychiatric Manifestations HP:0000752 (Hyperactivity)
HP:0000737 (Irritability)
Metabolic Features - Protein intolerance
Laboratory Abnormalities - HP:0001987 (hyperammonemia)
Hyperarginemia
DiHP:0003355 (Aminoaciduria) (arginuria, lysinuria, cystinuria, ornithinuria)
Orotic aciduria
Pyrimidinuria
Elevated CSF amino acids (arginine, ornithine, aspartate, threonine, glycine, and methionine)
Miscellaneous - Prevalence is estimated to be 1 in 1,100,000
Hyperarginemia
Diaminoaciduria (arginuria, lysinuria, cystinuria, ornithinuria)
Orotic aciduria
Pyrimidinuria
Increased CSF amino acids (arginine, ornithine, aspartate, threonine, glycine, and methionine)
ARHGAP31 610911 ADAMS-OLIVER SYNDROME 1; AOS1 100300   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Head HP:0000252 (microcephaly)
HP:0001057 (Aplasia cutis congenita) over parietal area
Eyes HP:0000565 (Esotropia)
HP:0000568 (Microphthalmia)
Mouth HP:0100333 (Unilateral cleft lip)
HP:0000175 (Cleft palate)
Cardiovascular Heart HP:0002564 (Congenital heart defect)s (in some patients)
HP:0001629 (Ventricular septal defect)
HP:0001631 (Atrial septal defect)
HP:0001642 (Pulmonary valve stenosis)
HP:0001636 (Tetralogy of Fallot)
Vascular HP:0004415 (Pulmonary artery stenosis)
HP:0002092 (Pulmonary hypertension)
Vascular malformations
Chest External Features Poland sequence
Breasts Accessory nipples
Genitourinary Internal Genitalia (Female) Imperforate vaginal hymen
Skeletal Skull Skull defect at vertex
Limbs Terminal transverse defects, asymmetric (minimal to absence of a limb)
Hands HP:0009803 (short fingers)
HP:0006101 (Finger syndactyly)
Feet HP:0006101 (Finger syndactyly)
Malformed toes
HP:0001762 ( Pes equinovarus)
Skin, Nails, Hair Skin HP:0001057 (Aplasia cutis congenita) over posterior parietal area
HP:0001057 (Aplasia cutis congenita) on trunk or limbs
HP:0000965 (Cutis marmorata)
Thin, hyperpigmented skin
Dilated scalp veins radiating from periphery of HP:0007385 (Scalp defect)
Nails HP:0001792 (Hypoplastic nails)
Hair Single-multiple round-oval areas of HP:0001596 (Alopecia) in parietal area
Neurologic Central Nervous System HP:0002084 (Encephalocele) (uncommon)
HP:0001249 (Intellectual disability) (uncommon)
HP:0012758 (neurodevelopmental delay)
Seizures
HP:0008947 (Hypotonia, early)
HP:0002119 (ventriculomegaly)
HP:0007229 (Periventricular calcifications)
HP:0006970 (Periventricular leukomalacia)
HP:0002079 (Hypoplasia of the corpus callosum)
HP:0002539 (Cortical dysplasia)
HP:0001302 (pachygyria)
HP:0002126 (Polymicrogyria)
Miscellaneous - HP:0003812 (Variable phenotype)
Phenotype is classically defined as aplasia cutis and transverse limb defects
 
ARHGDIA 601925 NEPHROTIC SYNDROME, TYPE 8; NPHS8 615244   4 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Ears HP:0000407 (sensorineural hearing loss) (in 1 Ashkenazi patient)
Eyes Cortical HP:0000618 (Blindness) (in 1 Moroccan patient)
Genitourinary Kidneys HP:0000100 (Nephrotic syndrome)
HP:0000083 (Renal failure), progressive
Abnormal glomeruli seen on biopsy
Diffuse HP:0001967 (mesangial sclerosis)
Hypercellularity
Immature podocytes
Foot process effacement
Thinning of the glomerular basement membrane
Swollen endothelial cells
Muscle, Soft Tissue - HP:0000969 (Edema)
Neurologic Central Nervous System HP:0001249 (Intellectual disability) (in 1 Ashkenazi patient)
Cortical HP:0000618 (Blindness) (in 1 Moroccan patient)
Seizures (in 1 Moroccan patient)
Laboratory Abnormalities - HP:0000093 (Proteinuria)
HP:0003073 (Hypoalbuminemia)
Miscellaneous - Onset in first weeks of life
Rapidly progressive
Fatal if renal transplant is not performed
 
ARHGEF15 608504 Epileptic encephalopathy   23647072 2 0  
ARHGEF9 300429 EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 8; EIEE8 #300607    1 Inheritance - HP:0001419 (X-linked recessive)
Neurologic Central Nervous System HP:0001276 (Muscle hypertonia)
HP:0002267 (Hyperekplexia)
Seizures, tonic, hyperekplectic
Seizures provoked by tactile stimulation or extreme emotion
Seizures are poorly controlled
Impaired psychomotor development
HP:0001249 (Intellectual disability), severe
Miscellaneous - HP:0003577 (Onset at birth)
 
ARID1A 603024 COFFIN-SIRIS SYNDROME 2; CSS214 614607   2 Inheritance -
HP:0000006 (Autosomal dominant)
Growth Height
HP:0004322 (Short stature) (in some patients)
Head and Neck Face
HP:0000280 (Coarse facies)
Ears
HP:0000377 (Dysplastic ears)
Eyes
HP:0000505 (Visual impairment)
HP:0000574 (Thick eyebrows)
HP:0000527 (Long eyelashes)
Nose
HP:0000431 (Broad nasal bridge)
HP:0000445 (Broad nose)
HP:0000463 (Anteverted nostrils)
Mouth
HP:0000154 (wide mouth)
HP:0000219 (Thin upper vermilion)
HP:0000179 (Thick lower vermilion)
HP:0000158 (Macroglossia)
Teeth
Delayed dentition
Cardiovascular Heart
HP:0002564 (Congenital heart defect)s
Abdomen Gastrointestinal
HP:0011968 (feeding difficulties)
Skeletal -
HP:0002750 (Delayed bone age)
Hands
HP:0009803 (short fingers)
HP:0009835 (Hypoplastic to absent terminal phalanges) (especially fifth finger)
Feet
Hypoplastic to absent terminal phalanges (especially fifth toe)
Skin, Nails, Hair Nails
HP:0001792 (Hypoplastic nails)
Hair
HP:0000294 (Low anterior hairline)
HP:0000998 (hypertrichosis)
HP:0002209 (Sparse scalp hair)
Neurologic Central Nervous System
HP:0001263 (Global developmental delay)
HP:0001249 (Intellectual disability)
HP:0000750 (Speech delay)
HP:0008947 (Hypotonia)
Seizures (in some patients)
Abnormal corpus callosum
 
ARID1B 614556 COFFIN-SIRIS SYNDROME 1; CSS1 135900 25356899 2 0  
ARNT2 606036 WEBB-DATTANI SYNDROME; WEDAS 615926   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0001510 (growth delay)
Head and Neck Head HP:0000252 (microcephaly), postnatal (up to -6.4 SD)
Face HP:0011220 (Prominent forehead)
Well-grooved philtrum
HP:0000278 (Retrognathia)
Eyes HP:0000490 (Deep-set eyes)
HP:0000618 (Blindness), postretinal
Abdomen Gastrointestinal HP:0002020 (Gastroesophageal reflux)
Genitourinary External Genitalia (Male) HP:0000028 (Cryptorchidism)
Kidneys HP:0000126 (Hydronephrosis)
HP:0000076 (Vesicoureteral reflux)
Bladder HP:0000011 (Neurogenic bladder)
Skeletal Pelvis HP:0002827 (Hip dislocations)
Neurologic Central Nervous System Global HP:0012758 (neurodevelopmental delay), severe
Seizures
HP:0001257 (Spasticity)
Abnormal hypothalamo-pituitary axis
Absent posterior pituitary bright spot
Thin pituitary stalk
Hypoplastic anterior pituitary gland
HP:0002079 (Thin corpus callosum)
Frontotemporal hypoplasia
HP:0012448 (Delayed myelination)
Endocrine Features -
Hypothalamic insufficiency
HP:0000824 (Growth hormone deficiency)
Adrenocorticotropin deficiency
Cortisol insufficiency
Thyroid stimulating hormone deficiency
HP:0003228 (Hypernatremia)
HP:0000873 (Diabetes insipidus)
HP:0000821 (Hypothyroidism), central
Laboratory Abnormalities - HP:0003228 (Hypernatremia)
Miscellaneous - Onset soon after birth
 
ARSA 607574 METACHROMATIC LEUKODYSTROPHY #250100   5 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes HP:0000648 (optic atrophy)
Abdomen Biliary Tract Gallbladder dysfunction
Cholecystitis
Genitourinary Bladder HP:0000020 (Urinary incontinence)
Neurologic Central Nervous System HP:0001268 (cognitive decline)
HP:0002371 (Loss of speech)
HP:0008947 (Hypotonia, early)
HP:0003324 (Muscle weakness)
HP:0001288 (Gait disturbance)
HP:0001265 (Hyporeflexia) (early)
HP:0001260 (Dysarthria)
HP:0007325 (generalized dystonia)
HP:0002072 (Chorea)
HP:0001251 (ataxia)
Spastic HP:0002445 (Tetraplegia)
HP:0001347 (Hyperreflexia) (later)
HP:0003487 (Extensor plantar responses) (later)
Seizures
HP:0001283 (Bulbar palsy)
Progression to HP:0002445 (Tetraplegia) and decerebrate state
Cerebral HP:0002500 (White matter abnormalities)
HP:0002922 (Elevated CSF protein)
Peripheral Nervous System Progressive HP:0001271 (polyneuropathy)
HP:0007305 (CNS demyelination)
EMG shows neuropathic changes
Delayed nerve conduction velocity
Behavioral Psychiatric Manifestations HP:0000708 (Behavioral disturbance)
HP:0000712 (Emotional lability)
HP:0001249 (Intellectual disability)
HP:0000738 (Hallucinations)
HP:0000746 (Delusions)
Disorganized thinking
Laboratory Abnormalities - Metachromatic deposits (sulfatide-containing) in central and peripheral nervous systems and visceral organs
Decreased arylsulfatase A (ARSA) activity in urine, leukocytes, fibroblasts
HP:0002922 (Increased CSF protein)
Increased urinary sulfatide excretion
Miscellaneous - Late infantile onset 6-24 months
Juvenile onset 4 years to puberty
Adult onset after puberty
Adult onset form usually presents with psychiatric manifestations
Pseudoarylsulfatase A deficiency is an allelic disorder with reduced levels of ARSA activity, but no neurologic manifestations
Increased protein (C)
Increased sulfatide (U)
ARX 300382 EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 1; EIEE1 #308350   1 Inheritance - HP:0001419 (X-linked recessive)
Head and Neck Head HP:0040195 (Decreased head circumference)
Respiratory - HP:0002094 (dyspnea)
Abdomen Gastrointestinal HP:0002015 (Dysphagia)
Neurologic Central Nervous System Seizures, intractable
HP:0002123 (Myoclonic seizures)
HP:0002521 (hypsarrhythmia)
Arrest of psychomotor development after seizure onset
HP:0001249 (Intellectual disability)
HP:0007325 (generalized dystonia)
Status dystonicus
HP:0001266 (Choreoathetosis)
Quadriplegic HP:0100660 (dyskinesia)
Axial HP:0008947 (Hypotonia, early)
HP:0001276 (Muscle hypertonia)
HP:0001347 (Hyperreflexia)
HP:0001257 (Spasticity)
HP:0002119 (ventriculomegaly)
MRI shows T2-weighted signals in the basal ganglia
Miscellaneous - Onset of seizures in first months of life (usually 4 to 7 months)
HP:0100660 (dyskinesia)s occur in a subset of patients later than seizures (6 to 12 months)
Males are most severely affected, but females can also be affected
 
ASAH1 613468 SPINAL MUSCULAR ATROPHY WITH PROGRESSIVE MYOCLONIC EPILEPSY; SMAPME #159950   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Face Facial HP:0003324 (Muscle weakness)
Mouth Tongue HP:0002380 (Fasciculations)
Respiratory - HP:0002093 (Respiratory insufficiency) due to HP:0003324 (Muscle weakness)
HP:0002205 (Recurrent respiratory infections)
Abdomen Gastrointestinal HP:0002015 (Dysphagia)
Skeletal Spine HP:0002650 (Scoliosis)
Muscle, Soft Tissue - HP:0003324 (Muscle weakness), proximal
HP:0003202 (Muscle atrophy)
HP:0003391 (Gowers sign)
HP:0002380 (Fasciculations)
Muscle biopsy showed neurogenic atrophy
EMG shows chronic denervation
Neurologic Central Nervous System Normal early psychomotor development
HP:0002355 (Difficulty walking)
HP:0002359 (Frequent falls)
Loss of independent ambulation
HP:0002322 (Resting tremor)
Seizures
Generalized seizures
HP:0002123 (Myoclonic seizures)
3-4 Hz slow sharp waves seen on EEG
Peripheral Nervous System HP:0001284 (Areflexia)
Laboratory Abnormalities - Normal serum creatine kinase
Miscellaneous - Onset of HP:0003324 (Muscle weakness) around age 5 years
Onset of seizures around 7 to 12 years
Seizures are sensitive to HP:0002883 (Hyperventilation)
HP:0003676 (Progressive disorder)
0
ASL 608310 ARGININOSUCCINIC ACIDURIA #207900   3 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Abdomen Liver HP:0001395 (Liver fibrosis)
HP:0002240 (Hepatomegaly)
Elevated serum glutamic oxaloacetic transaminase (SGOT)
Elevated serum glutamic pyruvic transaminase (SGPT)
Gastrointestinal HP:0011968 (feeding difficulties)
HP:0002038 (Protein avoidance)
HP:0002013 (Vomiting)
Skin, Nails, Hair Hair HP:0009886 (Trichorrhexis nodosa)
Dry HP:0002299 (brittle hair)
Neurologic Central Nervous System HP:0001251 (ataxia)
Coma
Seizures
HP:0002181 (Cerebral edema)
HP:0012758 (neurodevelopmental delay)
HP:0001249 (Intellectual disability)
Behavioral Psychiatric ManifestationsHP:0000737 (Irritability)
HP:0001254 (Lethargy)
Metabolic Features - HP:0001951 (episodic hyperammonemia)
HP:0001950 (Respiratory alkalosis)
Arginine deficiency
Laboratory Abnormalities - HP:0001987 (hyperammonemia)
High plasma citrulline (100-300 micromolar)
High plasma glutamine
Hepatic argininosuccinase deficiency
Argininosuccinicaciduria
Elevated serum glutamic oxaloacetic transaminase (SGOT)
Elevated serum glutamic pyruvic transaminase (SGPT)
Orotic aciduria
Miscellaneous - Onset in neonatal period or infancy
Prevalence is estimated to be 1 in 150,000
Increased citrulline (P)
Increased glutamine (P)
Argininosuccinicaciduria
Orotic aciduria
ASNS 108370 ASPARAGINE SYNTHETASE DEFICIENCY; ASNSD #615574   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000252 (microcephaly), progressive (up to -7 SD)
Face Receding forehead
HP:0000347 (Micrognathia)
Ears HP:0000400 (macrotia)
Eyes Cortical HP:0000618 (Blindness)
Respiratory - HP:0002093 (Respiratory insufficiency)
Abdomen Gastrointestinal HP:0011968 (feeding difficulties)
Skeletal Hands HP:0001176 (Large hands)
Feet HP:0001833 (Large feet)
Neurologic Central Nervous System HP:0004319 (nonprogressive encephalopathy), progressive
HP:0001263 (Delayed psychomotor development), profound
Axial HP:0008947 (Hypotonia, early)
Appendicular HP:0001276 (Muscle hypertonia)
Spastic HP:0002445 (Tetraplegia)
HP:0001347 (Hyperreflexia)
Seizures
Jitteriness
HP:0002267 (Hyperekplexia)
HP:0010851 (Burst suppression pattern) seen on EEG
Multiple independent spike foci
HP:0002521 (hypsarrhythmia)
Brain imaging shows HP:0002120 (Cortical atrophy)
HP:0002119 (ventriculomegaly)
HP:0012110 (hypoplasia of the pons)
HP:0001321 (Cerebellar hypoplasia)
HP:0002079 (Thin corpus callosum)
HP:0012448 (Delayed myelination)
HP:0002539 (Cortical dysplasia)
HP:0009879 (Simplified gyral pattern)
Laboratory Abnormalities - Decreased asparagine levels (in some patients)
Miscellaneous - HP:0003577 (prenatal onset) or at birth
HP:0003676 (Progressive disorder)
Death usually in infancy
Decreased asparagine
ASPA 608034 CANAVAN DISEASE #271900   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0040194 (Increased head circumference)
HP:0001476 (Delayed closure of anterior fontanelle)
Ears Deafness
Eyes HP:0000648 (optic atrophy)
HP:0000639 (Nystagmus)
HP:0000618 (Blindness)
Neurologic Central Nervous System Initial HP:0008947 (Hypotonia, early), followed by HP:0001257 (Spasticity)
Generalized seizures
HP:0002179 (Opisthotonus)
Loss of very early milestones
Decerebrate or decorticate posturing late
HP:0007305 (CNS demyelination) with white matter disease in internal capsule, external capsule, genu of corpus callosum, subcortical white matter, and posterior fossa
HP:0002283 (Generalized brain atrophy)
Laboratory Abnormalities - Spongy degeneration of brain on histology
Increased N-acetyl-L-aspartic acid (NAA) in urine, CSF, and blood
Reduced aspartoacylase activity in cultured skin fibroblasts
Miscellaneous - Normal first month
Onset of symptoms at 2-4 months
Prevalent in Ashkenazi Jews
Death within first decade
Increased N-acetyl-L-aspartic acid (NAA) (U, P, C)
ASPM 605481 MICROCEPHALY 5, PRIMARY, AUTOSOMAL RECESSIVE; MCPH5 #608716   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Head and Neck Head HP:0000252 (microcephaly) (head circumference 3-11 S.D. below mean)
Face HP:0000340 (Sloping forehead)
Ears CongenitalHP:0000410 (Hearing loss, mixed) (1 family)
Neurologic Central Nervous System HP:0001249 (Intellectual disability), mild to severe
HP:0001270 (Delayed motor development)
HP:0000750 (language delay)
Seizures (less common)
HP:0001274 (agenesis of corpus callosum) (less common)
Small cerebral cortex
HP:0009879 (Simplified gyral pattern)
HP:0002119 (ventriculomegaly)
HP:0002539 (Cortical dysplasia)
Behavioral Psychiatric Manifestations HP:0000752 (Hyperactivity)
HP:0007018 (Attention deficit hyperactivity disorder)
Miscellaneous - HP:0003577 (Onset at birth)
Some patients may show mild decrease in head circumference over time
 
ASS1 603470 CITRULLINEMIA, CLASSIC #215700   3 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Abdomen Liver HP:0002240 (Hepatomegaly)
HP:0001394 (liver cirrhosis) (in late-onset cases)
Gastrointestinal HP:0002038 (Protein avoidance)
HP:0002013 (Vomiting)
Neurologic Central Nervous System HP:0001254 (Lethargy)
HP:0001251 (ataxia)
Coma
Seizures
HP:0002181 (Cerebral edema)
HP:0012758 (neurodevelopmental delay)
HP:0001249 (Intellectual disability)
HP:0001297 (stroke) (rare)
Behavioral Psychiatric ManifestationsHP:0000737 (Irritability)
Metabolic Features - HP:0001951 (episodic hyperammonemia)
HP:0001950 (Respiratory alkalosis)
Laboratory Abnormalities - HP:0001987 (hyperammonemia)
High plasma citrulline (1000-5000 micromolar)
High plasma glutamine
Low plasma arginine
Orotic aciduria
Hepatic argininosuccinate synthetase deficiency
Miscellaneous - HP:0003812 (Variable phenotype)
Incidence of 1 in 57,000
Prevalence of 1 in 100,000
Neonatal onset
Patients may be asymptomatic, but are at risk for metabolic decompensation
Increased citrulline (P)
Increased glutamine (P)
Decreased arginine (P)
Orotic aciduria
ASXL1 612990 BOHRING-OPITZ SYNDROME; BOPS 605039   2 Inheritance - HP:0000006 (Autosomal dominant)
Growth Height HP:0004322 (short stature)
Other HP:0001511 (Intrauterine growth retardation)
HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000243 (Trigonocephaly)
HP:0000252 (microcephaly)
Face HP:0000347 (Micrognathia)
HP:0011220 (Prominent forehead)
HP:0000278 (Retrognathia)
HP:0000341 (Bitemporal narrowing)
HP:0000276 (Long face)
Facial HP:0001028 (Hemangioma)
Ears HP:0000369 (Low-set ears)
HP:0000358 (Posteriorly rotated ears)
Eyes HP:0000520 (Prominent eyes)
HP:0009891 (Hypoplastic orbital ridges)
HP:0000316 (Hypertelorism)
HP:0000582 (Upslanting palpebral fissures)
HP:0000486 (Strabismus)
HP:0000545 (Myopia)
Retinal abnormalities
Optic nerve abnormalities
Nose HP:0007965 (Broad nasal bridge)
Mouth HP:0000189 (Narrow palate)
HP:0000187 (Broad alveolar ridges)
HP:0100333 (Unilateral cleft lip)
HP:0000175 (Cleft palate)
Cardiovascular Heart HP:0001629 (Ventricular septal defect)
HP:0001631 (Atrial septal defect)
Chest Breasts HP:0006610 (Widely spaced nipples)
HP:0002558 (Supernumerary nipple)
Abdomen Pancreas Hyperechogenic pancreas
Gastrointestinal Severe HP:0002020 (Gastroesophageal reflux)
HP:0002566 (Malrotation)
HP:0011968 (feeding difficulties)
Genitourinary Ureters HP:0000076 (Vesicoureteral reflux)
Skeletal - HP:0004576 (large joint contractures)
HP:0001373 (joint dislocations)
Skull HP:0005487 (prominent metopic suture)
HP:0009891 (Hypoplastic orbital ridges)
Limbs Upper limb HP:0008905 (rhizomelia)
Unusual upper limb position (elbow and wrist flexion)
HP:0003083 (Radial head dislocations)
HP:0009487 (Ulnar deviation of hands)
Hands HP:0001169 (Broad hands)
HP:0006191 (Deep palmar crease)
HP:0006101 (Finger syndactyly)
HP:0001182 (Tapered fingers)
HP:0100490 (Camptodactyly)
Ulnar deviation of the metacarpophalangeal joints
Feet HP:0001869 (Deep plantar creases)
HP:0001831 (Short toes)
HP:0001845 (Overriding toes)
Skin, Nails, Hair Skin HP:0000960 (Sacral dimple)
Nevi flammei (philtrum, nape of neck, forehead)
Hair Long hair
HP:0100874 (Thick hair)
HP:0001007 (Hirsutism)
HP:0000294 (Low anterior hairline)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
HP:0001249 (Intellectual disability), profound
Seizures
HP:0008947 (Hypotonia, early)
HP:0001274 (agenesis of corpus callosum)
HP:0002079 (Hypoplasia of corpus callosum)
Focal nodular HP:0002282 (heterotopia)
Small brainstem
HP:0001305 (Dandy-Walker malformation)
Peripheral Nervous System HP:0012448 (Delayed myelination)
Prenatal Manifestations Amniotic Fluid HP:0001561 (Polyhydramnios)
Miscellaneous - All reported cases have occurred de novo
Death often occurs in childhood
 
ATIC 601731 AICAR TRANSFORMYLASE/IMP CYCLOHYDROLASE DEFICIENCY #608688   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000248 (Brachycephaly)
Face HP:0011220 (Prominent forehead)
Ears HP:0000369 (Low-set ears)
Eyes Congenital HP:0000618 (Blindness)
HP:0000648 (optic atrophy)
Nose HP:0000426 (High nasal bridge)
HP:0000463 (Anteverted nares)
Mouth HP:0000154 (Wide mouth)
HP:0000219 (Thin upper lip)
Cardiovascular Heart HP:0001631 (Atrial septal defect)
Genitourinary External Genitalia (Female) HP:0000057 (Clitoromegaly)
HP:0000063 (Fused labia minora)
Skin, Nails, Hair Skin Cutaneous dimples (knees, elbows, shoulders)
Neurologic Central Nervous System HP:0001249 (Intellectual disability), profound
Seizures
HP:0008947 (Hypotonia, early)
Laboratory Abnormalities - Positive urinary Bratton-Marshall test
Elevated urinary and CSF 5-amino-4-imidazolecarboxyamide (AICA-riboside)
Elevated erythrocyte AICAR (ZMP)
Deficient fibroblast AICAR-TF activity
Positive Bratton-Marshall test (U)
Increased 5-amino-4-imidazolecarboxyamide (AICA-riboside) (U)
ATM 607585 ATAXIA-TELANGIECTASIA; AT 208900   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Head and Neck Head HP:0000246 (sinusitis)
Respiratory Airways Bronchitis
HP:0002110 (Bronchiectasis)
Genitourinary Internal Genitalia (Male) HP:0000815 (Hypogonadism)
HP:0008669 (Impaired spermatogenesis)
Internal Genitalia (Female) HP:0000815 (Hypogonadism)
Skin, Nails, Hair Skin HP:0001009 (Cutaneous telangiectasia)
HP:0000957 (Cafe-au-lait spots)
Progeric skin changes
Sclerodermatous skin changes
Hair Progeric hair changes
Neurologic Central Nervous System Cerebellar cortical degeneration
cerebellar HP:0001251 (ataxia)
HP:0001315 (Reduced/absent deep tendon reflexes)
HP:0001260 (Dysarthria)
HP:0001266 (Choreoathetosis)
HP:0007325 (generalized dystonia)
HP:0001336 (myoclonus)
HP:0002322 (Resting tremor)
Seizures
HP:0000496 (Oculomotor abnormalities)
Endocrine Features - HP:0000823 (Delayed puberty)
HP:0000819 (Diabetes mellitus)
HP:0000833 (Glucose intolerance)
Immunology - HP:0000778 (Thymus hypoplasia)
Normal numbers of B cells
Defective B cell differentiation
HP:0001888 (Lymphocytopenia)
Reduced numbers of T cells
Reduced CD4+ T cells
Increased levels of T cells bearing gamma/delta antigen receptor
Reduced levels of cells with IgM receptors
Neoplasia - Non-Hodgkin lymphoma
Leukemia
Hodgkin lymphoma
Increased risk in heterozygotes
Laboratory Abnormalities - Increased levels of alpha fetoprotein
Increased levels of carcinoembryonic antigen
Reduced IgA levels
Reduced IgE levels
Reduced IgG levels, particularly the IgG2 subclass
Monomeric IgM
Immunoglobulin antibodies present
CD4+/CD8+ ratio is reversed
Miscellaneous - HP:0001251 (ataxia) becomes evident at the end of the first year of life
HP:0001009 (Telangiectasia) become evident between the second and eighth year of life
Hypersensitivity to ionizing radiation
Variant AT may present with HP:0007325 (generalized dystonia) only
 
ATN1 607462 DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY; DRPLA #125370    2 Inheritance - HP:0000006 (Autosomal dominant)
Neurologic Central Nervous System cerebellar HP:0001251 (ataxia)
HP:0001336 (myoclonus)
Seizures
HP:0001266 (Choreoathetosis)
HP:0000726 (Dementia)
Degeneration of the dentatorubral and pallidoluysian systems
Miscellaneous - Mean age of onset 30 years (range first to seventh decade)
HP:0003743 (Genetic anticipation)
Phenotypic heterogeneity
 
ATP13A2 610513 KUFOR-RAKEB SYNDROME; KRS #606693   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Face HP:0000298 (Mask-like facies)
Eyes HP:0000605 (Supranuclear gaze palsy)
Oculogyric dystonic spasms
HP:0000514 (Slow saccades)
Nose HP:0000458 (Anosmia)
HP:0004409 (Hyposmia)
Neck HP:0000473 (Torticollis)
Neurologic Central Nervous System HP:0001300 (Parkinsonism)
HP:0002375 (Hypokinesia)
Akinesia
HP:0000298 (Mask-like facies)
HP:0002063 (Rigidity)
Anarthria
Festinating (Parkinsonian) gait
Facial-faucial-finger mini-HP:0001336 (myoclonus) (FFF)
HP:0001257 (Spasticity)
HP:0002172 (Postural instability)
Mild HP:0002385 (Paraparesis)
HP:0001347 (Hyperreflexia)
HP:0003487 (Extensor plantar responses)
HP:0007256 (Pyramidal tract signs)
HP:0002071 (extrapyramidal signs)
HP:0007325 (generalized dystonia)
HP:0001336 (myoclonus)
Seizures (in some patients)
HP:0001268 (cognitive decline)
HP:0000726 (Dementia) (in some patients)
Generalized cerebral, cerebellar, and HP:0007366 (Brainstem atrophy), progressive
Flattening of the caudate
Atrophy of pyramids
Brain iron accumulation in the basal ganglia (in some patients)
Peripheral Nervous System Distal sensory impairment (in some patients)
Behavioral Psychiatric Manifestations HP:0000738 (Hallucinations)
HP:0000725 (Psychotic episodes)
HP:0000718 (Aggressive behavior)
Laboratory Abnormalities - Cytoplasmic lamellar inclusions consistent with neuronal ceroid lipofuscinosis (in some patients)
Miscellaneous - Average age of onset 13 years
Rapidly progressive (6-24 months)
Favorable initial response to L-DOPA
Therapy-induced HP:0100660 (dyskinesia)s
Cytoplasmic lamellar inclusions
ATP1A2 182340 ALTERNATING HEMIPLEGIA OF CHILDHOOD 1; AHC1 #104290   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Eyes HP:0000496 (oculomotor abnormalities)
HP:0000639 (Nystagmus)
Upward eye deviation during episodes
Neurologic Central Nervous System HP:0002301 (Hemiplegia), episodic
HP:0002445 (quadriplegia), episodic
HP:0001268 (cognitive decline), progressive
HP:0001249 (Intellectual disability)
HP:0007325 (generalized dystonia)
HP:0001266 (Choreoathetosis)
HP:0002459 (Dysautonomia) affecting limbs during episodes
Generalized HP:0002069 (Tonic-clonic seizures)in 50%
HP:0001268 (Cognitive decline)ion after prolonged episodes
Headache is usually not a symptom
Miscellaneous - Onset before 18 months of age
Favorable response to flunarizine
 
ATP1A3 182350 ALTERNATING HEMIPLEGIA OF CHILDHOOD 2; AHC2 #614820   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Eyes HP:0000496 (oculomotor abnormalities)
Neurologic Central Nervous System HP:0002301 (Hemiplegia), episodic
HP:0002445 (quadriplegia), episodic
HP:0012758 (neurodevelopmental delay)
HP:0001268 (cognitive decline), progressive
HP:0007325 (generalized dystonia)
HP:0001266 (Choreoathetosis)
HP:0001251 (ataxia)
HP:0002459 (Dysautonomia)
Seizures
HP:0002133 (Status epilepticus)
Interictal neurologic impairment
Miscellaneous - Onset before 18 months of age
HP:0003828 (Variable severity) and progression
Flunarizine treatment may be beneficial
Most cases due to de novo mutation
 
ATP2A2 108740 DARIER-WHITE DISEASE; DAR #124200   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Mouth Recurrent parotid gland swelling
Oral mucosal lesions (15% of patients)
Skin, Nails, Hair Skin Brown, warty keratotic HP:0200034 (Papules) (trunk, scalp, forehead, flexural areas)
HP:0010610 (Palmar pits)
HP:0010612 (Plantar pits)
Odoriferous,, hypertrophic plaques
Keratotic plaques (palms)
Hemorrhagic palmar and plantar macules (uncommon)
Acrokeratosis verruciformis-like lesions on dorsum of hands
Skin Histology Acantholysis (cell separation) in the suprabasal layer of the epidermis with premature differentiation and hyperkeratinization of the epidermis
Electron Microscopy Loss of desmosomal attachments and perinuclear aggregation of keratin filaments
Nails Fingernails involved more often than toenails
Longitudinal white or red subungual streaks
Distal V-shaped notching
Nail fragility
Longitudinal ridging
Subungual hyperkeratotic fragments
Neurologic Central Nervous System HP:0001249 (Intellectual disability), mild
Seizures
Behavioral Psychiatric Manifestations Schizophrenia
Bipolar disorder
Miscellaneous - Age of onset, 6-20 years
Skin lesions exacerbated by heat, exercise (sweating), and sunlight
Acral hemorrhagic variant
Itch, pain, and body malodor often
Allelic to acrokeratosis verruciformis (101900)
 
ATP5A1 164360 COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 22; COXPD22 #616045   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001511 (Intrauterine growth retardation)
HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000252 (microcephaly)
Cardiovascular Heart HP:0001635 (Congestive heart failure)
Vascular HP:0002092 (Pulmonary hypertension)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Decreased activities of several mitochondrial respiratory enzymes
Mitochondrial DNA depletion
Neurologic Central Nervous System HP:0004319 (nonprogressive encephalopathy)
Seizures
Laboratory Abnormalities - Increased serum alanine
HP:0003577 (Onset at birth)
Death in the first years of life
Increased lactate (P)
ATP6AP2 300556 MENTAL RETARDATION, X-LINKED, SYNDROMIC, HEDERA TYPE; MRXSH #300423    2 Inheritance - HP:0001419 (X-linked recessive)
Neurologic Central Nervous System HP:0001270 (Delayed motor development)
HP:0000750 (Language delay)
HP:0001249 (Intellectual disability)
HP:0002069 (Tonic-clonic seizures)
'Drop' attacks
Miscellaneous - HP:0003593 (Onset in infancy)
 
ATP6V0A2 611716 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIA; ARCL2A #219200   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001511 (Intrauterine growth retardation) (IUGR)
HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0011800 (Midface hypoplasia)
HP:0000343 (Long philtrum)
HP:0012368 (Flat face)
Ears HP:0000369 (Low-set ears)
Eyes HP:0000494 (Downslanting palpebral fissures)
HP:0000486 (Strabismus)
HP:0000545 (Myopia)
Nose HP:0003196 (Short nose)
HP:0000463 (Anteverted nares)
Mouth HP:0000160 (Small mouth)
HP:0000218 (High-arched palate)
Teeth HP:0000670 (Dental caries)
Abdomen Gastrointestinal HP:0011968 (feeding difficulties) in infancy
Skeletal - HP:0002761 (Generalized joint laxity)
Skull HP:0000260 (Wide anterior fontanel)
HP:0000270 (Delayed closure of fontanel)
Pelvis congenital HP:0002827 (Hip dislocations)
Skin, Nails, Hair Skin HP:0000973 (Cutis laxa)
HP:0001582 (Loose redundant skin)
Excessive skin folds
Skin Histology Abnormal, broken, shortened elastic fibers
Decreased amount of elastin
Hair Sparse, HP:0002299 (brittle hair)
HP:0002208 (Coarse hair)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
HP:0009125 (Lipodystrophy)
Abnormal distribution of subcutaneous fat
Neurologic Central Nervous System HP:0001270 (Delayed motor development)
HP:0001249 (Intellectual disability)
Seizures
HP:0008947 (Hypotonia, early)
Partial HP:0001302 (pachygyria)
Cobblestone HP:0001339 (Lissencephaly), posterior frontal and parietal regions
HP:0009879 (Simplified gyral pattern)
HP:0002126 (Polymicrogyria)
HP:0001305 (Dandy-Walker malformation)
Laboratory Abnormalities - Abnormal isoelectric focusing of serum transferrin
Defect in N- and O-glycosylation
Miscellaneous - Skin abnormalities tend to decrease with age
Isoelectric focusing of serum transferrin (defect in N- and O-glycosylation)
ATP7A 300011 MENKES DISEASE #309400   1 Inheritance - HP:0001419 (X-linked recessive)
Growth Height HP:0004322 (short stature)
Other HP:0001511 (Intrauterine growth retardation)
Head and Neck Head HP:0000252 (microcephaly)
HP:0000248 (Brachycephaly)
HP:0002645 (Wormian bones)
Face Pudgy cheeks
Cardiovascular Vascular HP:0002170 (Intracranial hemorrhage)
Skeletal - HP:0000939 (Osteoporosis)
HP:0001388 (Joint laxity)
Skull HP:0002645 (Wormian bones)
Limbs HP:0003016 (Metaphyseal widening) with HP:0005054; spurs
Skin, Nails, Hair Skin HP:0007513 (Generalized hypopigmentation)
HP:0000973 (Skin laxity)
Hair Steely, kinky, HP:0008070 (Sparse hair)
Twisted and partial breaks on magnification
Neurologic Central Nervous System HP:0001268 (Cognitive decline)
HP:0001276 (Muscle hypertonia)
HP:0001249 (Intellectual disability)
Seizures
HP:0002170 (Intracranial hemorrhage)
HP:0002045 (Hypothermia)
Laboratory Abnormalities - Low copper and ceruloplasmin
Miscellaneous - Classic severe form shows onset at 2 to 3 months of age
Early death (usually by 3 years of age)
A milder form has also been reported
Female carriers may have subtle manifestations
Incidence ranges from 1 in 40,000 to 1 in 350,000 births
Decreased copper and ceruloplasmin (P)
ATP7B 606882 WILSON DISEASE #277900   4 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes Kayser-Fleischer ring
Abdomen Liver Atypical or prolonged HP:0012115 (Hepatitis)
HP:0001394 (liver cirrhosis)
Hepatic coma
HP:0002240 (Hepatomegaly)
HP:0001399 (Liver failure)
High liver copper
Gastrointestinal Esophageal varices
Genitourinary Kidneys HP:0000124 (Renal tubular dysfunction)
HP:0000787 (Nephrolithiasis)
Skeletal - HP:0000939 (Osteoporosis)
HP:0002749 (Osteomalacia)
HP:0000934 (Chondrocalcinosis)
Limbs HP:0002758 (Osteoarthritis)
HP:0001388 (Joint laxity)
Neurologic Central Nervous System HP:0002322 (Resting tremor)
HP:0001260 (Dysarthria)
HP:0002015 (Dysphagia)
HP:0000751 (Personality change)
HP:0000726 (Dementia)
HP:0002275 (Poor motor coordination)
HP:0007325 (generalized dystonia)
HP:0002307 (Drooling)
Peripheral Nervous System Mixed demyelinating and axonal HP:0001271 (polyneuropathy) (rare)
Endocrine Features - HP:0000829 (Hypoparathyroidism)
Hematology - Hemolytic HP:0001903 (Anemia)
Laboratory Abnormalities - Low serum ceruloplasmin
High nonceruloplasmin-bound serum copper
High urinary copper
HP:0000093 (Proteinuria)
HP:0003355 (Aminoaciduria)
HP:0003076 (Glucosuria)
Uricaciduria
HP:0003109 (Hyperphosphaturia)
HP:0002150 (Hypercalciuria)
Miscellaneous - Incidence in United States of 1 in 55,000
Incidence worldwide of 1 in 30,000 to 50,000
Decreased ceruloplasmin (P)
Increased copper (U)
ATR 601215 SECKEL SYNDROME 1; SCKL1 #210600   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature), proportionate
Weight Average birth weight 1540g
Other HP:0001511 (Intrauterine growth retardation)
HP:0008897 (Postnatal growth retardation) (-7 S.D.)
Head and Neck Head HP:0000252 (microcephaly), severe
HP:0000237 (Small anterior fontanel)
Face HP:0000340 (Sloping forehead)
HP:0000347 (Micrognathia)
HP:0000324 (Facial asymmetry)
Ears HP:0000369; Low-set, HP:0000377 (Dysplastic ears)
Absence of earlobe
Eyes Relatively HP:0001090 (Large eyes)
HP:0000494 (Downslanting palpebral fissures)
HP:0000486 (Strabismus)
HP:0000581 (Blepharophimosis)
Nose HP:0000448 (Large nose)
HP:0000444 (Beaked nose)
Mouth HP:0000175 (Cleft palate)
HP:0000218 (High-arched palate)
Teeth Selective HP:0009804 (tooth agenesis)
HP:0006297 (Enamel hypoplasia)
Class II HP:0000689 (Dental malocclusion)
HP:0000678 (Dental crowding)
Chest Ribs, Sternum, Clavicles and Scapulae 11 pairs of ribs
Genitourinary External Genitalia (Male) HP:0000047 (Hypospadias)
External Genitalia (Female) HP:0000057 (Clitoromegaly)
Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
Skeletal - HP:0002750 (Delayed bone age)
Spine HP:0002650 (Scoliosis)
Pelvis HP:0002827 (Hip dislocations)
Limbs HP:0006434 (Hypoplasia of proximal radius)
HP:0003083 (Radial head dislocations)
HP:0006442 (Hypoplasia of proximal fibula)
Elbow flexion contracture
Aberrant patellae
Hands HP:0004209 (Fifth finger clinodactyly)
HP:0000954 (Single transverse palmar crease)
HP:0010583 (Ivory epiphyses) (phalanges)
HP:0010579 (Cone-shaped epiphyses) (phalanges)
Abnormal finger flexion creases
Feet HP:0001852 (Sandal gap)
HP:0001883 (Talipes)
HP:0001763 (pes planus)
Skin, Nails, Hair Skin Abnormal finger flexion creases
HP:0000954 (Single transverse palmar crease)s
Neurologic Central Nervous System HP:0001249 (Intellectual disability)
Seizures
HP:0001302 (pachygyria)
Arachnoidal cysts
Large basal ganglia
HP:0006817 (Aplasia/Hypoplasia of the cerebellar vermis)
Behavioral Psychiatric Manifestations HP:0000752 (Hyperactivity)
Hematology - HP:0001876 (Pancytopenia)
Increased sister chromatid exchange
Miscellaneous - Half of cases show retarded head circumference equal to height retardation
Other half show head circumference more retarded than height
 
ATRX 300032 MENTAL RETARDATION-HYPOTONIC FACIES SYNDROME, X-LINKED, 1; MRXHF1 #309580   2 Inheritance - HP:0001419 (X-linked recessive)
Growth Height HP:0004322 (short stature)
Weight HP:0001513 (Obesity), mild (rare)
Other HP:0008897 (Postnatal growth retardation)
Head and Neck Head HP:0000252 (microcephaly)
HP:0000268 (Dolichocephaly)
Face HP:0011800 (Midface hypoplasia)
HP:0000341 (Bitemporal narrowing)
HP:0000322 (Short philtrum)
HP:0000347 (Micrognathia)
HP:0000280 (Coarse facies)
Ears HP:0000369 (Low-set ears)
HP:0008551 (Small ears)
Everted ears
HP:0000358 (Posteriorly rotated ears)
HP:0000396 (overfolded ears)
HP:0000407 (Sensorineural hearing loss) (less common)
Eyes HP:0000286 (Epicanthus)
HP:0000316 (Hypertelorism)
HP:0000582 (Upslanting palpebral fissures)
HP:0000577 (Exotropia) (less common)
HP:0000508 (Ptosis)
HP:0000648 (optic atrophy)
Nose Flat, HP:0007965 (Broad nasal bridge)
HP:0005280 (depressed nasal bridge)
Triangular nasal tip
HP:0000463 (Anteverted nostrils)
Mouth 'Carp-like' mouth
HP:0000194 (Open mouth)
HP:0000154 (wide mouth)
Short, HP:0000219 (Thin upper lip)
Inverted V-shaped upper lip
HP:0000179 (Thick lower lip vermilion)
HP:0000218 (High-arched palate)
HP:0010808 (Protruding tongue)
HP:0002307 (Drooling)
Teeth HP:0000687; Widely-spaced upper incisors
Neck HP:0000470 (Short neck) (less common)
Abdomen Gastrointestinal HP:0002020 (Gastroesophageal reflux)
HP:0002013 (Vomiting)
HP:0002019 (Constipation)
Gut dysmotility
Genitourinary External Genitalia (Male) HP:0000815 (Hypogonadism)
HP:0008734 (Testicular hypoplasia)
HP:0000046 (Hypoplastic scrotum)
HP:0000054 (Small penis)
HP:0000047 (Hypospadias)
Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
Kidneys HP:0000089 (Renal hypoplasia) (less common)
Bladder HP:0000076 (Vesicoureteral reflux) (less common)
Skeletal - HP:0002750 (Delayed bone age)
Spine HP:0002751 (kyphoscoliosis) (approximately 30%)
Limbs HP:0002857 (Genua valga)
Hands Slender, HP:0001182 (tapered fingers)
HP:0009803 (short fingers)
HP:0004209 (Fifth finger clinodactyly) of isolated digits
Feet HP:0001762 ( Pes equinovarus)
TaliHP:0001848 (Pes calcaneovalgus)
HP:0001763 (pes planus)
Neurologic Central Nervous System HP:0001249 (Intellectual disability), severe, profound
HP:0008947 (Hypotonia, early), early
HP:0001276 (Muscle hypertonia) of lower limbs, later
HP:0001347 (Hyperreflexia)
Seizures (in 35%)
Behavioral Psychiatric Manifestations HP:0000749 (Paroxysmal bursts of laughter)
Repetitive, self-stimulatory behavior using upper limbs
Fingers in mouth
HP:0000752 (Hyperactivity)
Self-absorbed
Hematology - Absence of Hb H inclusions in red blood cells
Miscellaneous - HP:0003812 (Variable phenotype)
Alpha-thalassemia/HP:0001249 (Intellectual disability) syndrome (301040) is an allelic disorder
 
ATXN10 611150 SPINOCEREBELLAR ATAXIA 10; SCA10 #603516   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Eyes HP:0000639 (Nystagmus)
HP:0000496 (oculomotor abnormalities)
Abdomen Gastrointestinal HP:0002015 (Dysphagia)
Genitourinary Bladder HP:0000012 (Urinary urgency)
HP:0000020 (Urinary incontinence)
Neurologic Central Nervous System cerebellar HP:0001251 (ataxia), progressive
HP:0002066 (gait ataxia)
HP:0002311 (Incoordination)
HP:0002070 (limb ataxia)
HP:0001260 (Dysarthria)
HP:0002168 (Scanning speech)
HP:0001310 (Dysmetria)
HP:0002075 (Dysdiadochokinesis)
Seizures
HP:0007256 (Pyramidal tract signs)
HP:0002071 (extrapyramidal signs)
HP:0001347 (Hyperreflexia)
HP:0100543 (Cognitive impairment)
HP:0000726 (Dementia)
HP:0001272 (Cerebellar atrophy)
Peripheral Nervous System HP:0040129 (Nerve conduction abnormalities)
Behavioral Psychiatric Manifestations HP:0000716 (Depression)
Miscellaneous - Age at onset 14 to 44 years
Patients of Brazilian origin have a pure HP:0001272 (Cerebellar atrophy)
HP:0003743 (Genetic anticipation)
Reduced penetrance
Normal alleles have 10 to 29 repeats and pathologic alleles have 400 to 4,500 repeats
 
AUH 600529 3-METHYLGLUTACONIC ACIDURIA, TYPE I; MGCA1 #250950   4 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Eyes HP:0000648 (optic atrophy)
Genitourinary Bladder HP:0000020 (Urinary incontinence) (adult)
Neurologic Central Nervous System HP:0001263 (global developmental delay) (in some patients)
HP:0001270 (Delayed motor development)
Spastic HP:0002445 (quadriplegia)
HP:0007325 (generalized dystonia)
HP:0002305 (Athetosis)
cerebellar HP:0001251 (ataxia)
HP:0100543 (Cognitive impairment)
HP:0001347 (Hyperreflexia)
HP:0000750 (language delay)
HP:0000736 (Short attention span)
HP:0002373 (febrile seizures)
HP:0001260 (Dysarthria)
HP:0002283 (global brain atrophy), progressive
Basal ganglia atrophy, progressive
HP:0002352 (leukoencephalopathy)
Metabolic Features - HP:0001942 (metabolic acidosis)
Laboratory Abnormalities - Increased urinary 3-methylglutaconic acid
Increased urinary hydroxyisovaleric acid
Decreased activity of 3-methylglutaconyl-CoA hydratase
Miscellaneous - HP:0003812 (Variable phenotype)
Some patients have no clinical symptoms and are detected by routine newborn screening
HP:0003593 (Onset in infancy)
Adult onset of symptoms has been reported
Metabolic acidosis
Increased 3-methylglutaconic acid (U)
Increased hydroxyisovaleric acid (U)
AVPR2 300538 NEPHROGENIC SYNDROME OF INAPPROPRIATE ANTIDIURESIS; NSIAD 300539   2 Inheritance - HP:0001419 (X-linked recessive)
Cardiovascular Vascular Systolic HP:0000822 (Hypertension), mild
Neurologic Central Nervous System Seizures
Behavioral Psychiatric ManifestationsHP:0000737 (Irritability)
Laboratory Abnormalities - HP:0002902 (Hyponatremia)
Decreased serum osmolality
Inappropriately increased urine osmolality
Increased urinary sodium
Decreased serum BUN
Mildly decreased serum creatinine
Decreased plasma renin activity
Normal aldosterone
Euvolemia
Undetectable serum arginine vasopressin, or antidiuretic hormone (ADH, AVP, 192340)
Miscellaneous - Onset within first 3 months of life
Normal neonatal course
Caused by constitutive activation of the AVPR2 receptor
 
B3GLCT 610308 PETERS-PLUS SYNDROME 261540   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0001518 (Small for gestational age) (63%)
Adult male height 141-155cm
Adult female height 128-151cm
HP:0008873 (short-limb short stature)
Weight Birthweight < 3rd percentile (87%)
Other HP:0001511 (Intrauterine growth retardation)
HP:0008897 (Postnatal growth retardation)
Head and Neck Head HP:0000252 (microcephaly) (22%)
HP:0000256 (Macrocephaly) (8%)
HP:0000260 (Wide anterior fontanel) (birth)
HP:0001363 (craniosynostosis)
Face HP:0000311 (Round face) (childhood)
HP:0011220 (Prominent forehead)
HP:0000343 (Long philtrum)
HP:0000347 (Micrognathia)
Ears Small, HP:0000377 (Dysplastic ears)
HP:0004467 (Preauricular pit)
HP:0000402 (Narrow auditory canals)
HP:0000411 (Prominent ears)
Eyes HP:0000316 (Hypertelorism)
HP:0000659 (Peters anomaly)
Anterior chamber cleavage disorder
HP:0000639 (Nystagmus)
HP:0000508 (Ptosis)
HP:0000501 (Glaucoma)
HP:0000582 (Upslanting palpebral fissures)
HP:0000518 (Cataracts)
HP:0000545 (Myopia)
Iris HP:0000589 (coloboma)
HP:0000480 (Retinal coloboma)
Mouth HP:0000233 (HP:0000233 (Thin vermilion border) border)
HP:0002263 (Cupid-bow shaped upper lip)
HP:0100333 (Unilateral cleft lip)
HP:0000175 (Cleft palate)
Teeth Absent upper lateral incisors
Abnormally pointed upper lateral incisors
Neck HP:0000475 (Broad neck)
HP:0000465 (Webbed neck)
Cardiovascular Heart HP:0001631 (Atrial septal defect)
HP:0001629 (Ventricular septal defect)
HP:0001642 (Pulmonary stenosis)
Chest Ribs, Sternum, Clavicles and Scapulae HP:0000767 (HP:0000766 (Pectus deformities) excavatum)
Breasts HP:0006610 (Widely spaced nipples)
Abdomen External Features HP:0001540 (Diastasis recti)
HP:0001537 (Umbilical hernia)
Biliary Tract Double gallbladder
Gastrointestinal HP:0011968 (feeding difficulties)
Genitourinary External Genitalia (Male) HP:0000047 (Hypospadias)
Abnormal foreskin
External Genitalia (Female) HP:0000059 (Hypoplastic labia majora)
HP:0000060 (Hypoplastic clitoris)
Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
Internal Genitalia (Female) Rudimentary vagina
HP:0000013 (Rudimentary uterus)
Kidneys HP:0000126 (Hydronephrosis)
Kidney duplication
Ureters HP:0000073 (duplicated ureters)
Skeletal - HP:0001388 (Joint laxity) (except elbow)
Spine HP:0002650 (Scoliosis)
HP:0002937 (Hemivertebrae)
Vertebral segmentation defects
Pelvis Square pelvis
Flat iliac crests
Limbs HP:0008905 (rhizomelia)
Decreased elbow mobility
Hands Broad, HP:0004279 (Short hands)
HP:0004209 (Fifth finger clinodactyly)
HP:0006101 (Finger syndactyly)
HP:0000954 (Single transverse palmar crease)s
HP:0010049 (Short metacarpal)
HP:0009623 (Proximally placed thumbs)
Feet Broad, HP:0001773 (Small feet)
HP:0001761 (Pes cavus)
HP:0010743 (Short metatarsal)
Deep foot creases
Skin, Nails, Hair Skin HP:0000954 (Single transverse palmar crease)s
Deep foot creases
Hair Facial HP:0000998 (hypertrichosis)
Neurologic Central Nervous System Mild-severe HP:0001249 (Intellectual disability) (20%)
Seizures
HP:0001274 (Agenesis of corpus callosum)
HP:0000238 (Hydrocephalus)
HP:0002119 (ventriculomegaly)
HP:0002283 (Generalized brain atrophy)
Prenatal Manifestations Amniotic Fluid HP:0001561 (Polyhydramnios)
0
B4GAT1 605517 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 13; MDDGA13 615287   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes HP:0007973 (Retinal dysplasia)
Genitourinary External Genitalia (Male) HP:0008734 (Testicular hypoplasia)
Kidneys HP:0000110 (Renal dysplasia)
HP:0000107 (Renal cysts)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early), severe
Muscle biopsy shows decreased glycosylation of alpha-dystroglycan
HP:0003560 (Muscular dystrophy)
Neurologic Central Nervous System HP:0001263 (Lack of psychomotor development)
HP:0000238 (Hydrocephalus)
HP:0002119 (ventriculomegaly)
Seizures
HP:0001274 (agenesis of corpus callosum)
HP:0002365 (Brainstem hypoplasia)
HP:0001321 (Cerebellar hypoplasia)
HP:0002539 (Cortical dysplasia)
Cobblestone HP:0001339 (Lissencephaly)
Nodular HP:0002282 (heterotopia)
HP:0001305 (Dandy-Walker malformation)
Laboratory Abnormalities - HP:0003236 (Increased serum creatine kinase)
HP:0003577 (prenatal onset)
Early death
Increased serum creatine kinase
BCAP31 300398 DEAFNESS, DYSTONIA, AND CEREBRAL HYPOMYELINATION; DDCH 300475   2 Inheritance - HP:0001419 (X-linked recessive)
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0001999 (Dysmorphic features)
Ears HP:0000407 (Sensorineural hearing loss)
Eyes HP:0000486 (Strabismus)
HP:0000648 (optic atrophy) (in some patients)
Neurologic Central Nervous System HP:0001249 (Intellectual disability), severe
HP:0001263 (Lack of psychomotor development)
HP:0007325 (generalized dystonia)
HP:0007256 (Pyramidal tract signs)
HP:0002445 (quadriplegia)
Seizures (in some patients)
HP:0003429 (Hypomyelination)
HP:0002283 (global brain atrophy)
HP:0001272 (Cerebellar atrophy)
Laboratory Abnormalities - HP:0002910 (HP:0002910 (abnormal liver enzymes) tests) during illness
Miscellaneous - Early death may occur
 
BCKDHA 608348 MAPLE SYRUP URINE DISEASE; MSUD #248600   3 Inheritance - HP:0000007 (Autosomal recessive)
Abdomen Pancreas HP:0001733 (Pancreatitis)
Gastrointestinal HP:0011968 (feeding difficulties)
HP:0002013 (Vomiting)
Neurologic Central Nervous System HP:0001254 (Lethargy)
Seizures
HP:0001251 (ataxia)
Coma
HP:0001249 (Intellectual disability) if untreated
HP:0001276 (Muscle hypertonia)
HP:0008947 (Hypotonia, early)
HP:0002181 (Cerebral edema)
HP:0000738 (Hallucinations)
Brain MRI shows diffusion abnormalities
White matter signal abnormalities in various brain regions
Metabolic Features - Life-threatening metabolic decompensation
HP:0001946 (Ketosis)
HP:0001943 (Hypoglycemia)
HP:0003128 (Lactic acidosis) in E3-deficiency
Laboratory Abnormalities - Elevated plasma branched chain amino acids (leucine, isoleucine, valine)
Maple syrup urine odor
Branched chain ketoaciduria (alpha-keto isocaproate, alpha-keto-beta methylisovalerate, alpha-keto isovalerate)
Elevated plasma alloisoleucine
Positive urine DNPH screening test
Miscellaneous - Five clinical variants of MSUD unassociated with genotype
(1) Classic severe (onset of symptoms 4 to 7 days of age)
(2) Intermittent
(3) Intermediate
(4) Thiamine-responsive form
(5) Dihydrolipoyl dehydrogenase (E3)-deficient
Worldwide incidence of 1 in 185,000 live births
In inbred Old Order Mennonite population of Lancaster County, MSUD prevalence is 1/176 newborns
Death in untreated children
Increased branched chain amino acids (leucine, isoleucine, valine) (P)
Branched chain ketoaciduria (alpha-keto isocaproate, alpha-keto-beta methylisovalerate, alpha-keto isovalerate)
Increased alloisoleucine(P)
Positive urine DNPH screening test
BCKDHB 248611 MAPLE SYRUP URINE DISEASE; MSUD #248600   3 Inheritance - HP:0000007 (Autosomal recessive)
Abdomen Pancreas HP:0001733 (Pancreatitis)
Gastrointestinal HP:0011968 (feeding difficulties)
HP:0002013 (Vomiting)
Neurologic Central Nervous System HP:0001254 (Lethargy)
Seizures
HP:0001251 (ataxia)
Coma
HP:0001249 (Intellectual disability) if untreated
HP:0001276 (Muscle hypertonia)
HP:0008947 (Hypotonia, early)
HP:0002181 (Cerebral edema)
HP:0000738 (Hallucinations)
Brain MRI shows diffusion abnormalities
White matter signal abnormalities in various brain regions
Metabolic Features - Life-threatening metabolic decompensation
HP:0001946 (Ketosis)
HP:0001943 (Hypoglycemia)
HP:0003128 (Lactic acidosis) in E3-deficiency
Laboratory Abnormalities - Elevated plasma branched chain amino acids (leucine, isoleucine, valine)
Maple syrup urine odor
Branched chain ketoaciduria (alpha-keto isocaproate, alpha-keto-beta methylisovalerate, alpha-keto isovalerate)
Elevated plasma alloisoleucine
Positive urine DNPH screening test
Miscellaneous - Five clinical variants of MSUD unassociated with genotype
(1) Classic severe (onset of symptoms 4 to 7 days of age)
(2) Intermittent
(3) Intermediate
(4) Thiamine-responsive form
(5) Dihydrolipoyl dehydrogenase (E3)-deficient
Worldwide incidence of 1 in 185,000 live births
In inbred Old Order Mennonite population of Lancaster County, MSUD prevalence is 1/176 newborns
Death in untreated children
Increased branched chain amino acids (leucine, isoleucine, valine) (P)
Branched chain ketoaciduria (alpha-keto isocaproate, alpha-keto-beta methylisovalerate, alpha-keto isovalerate)
Increased alloisoleucine(P)
Positive urine DNPH screening test
BCKDK 614901 BRANCHED-CHAIN KETO ACID DEHYDROGENASE KINASE DEFICIENCY; BCKDKD #614923   3 0 Decreased branched chain amino acids
BCL10 603517 IMMUNODEFICIENCY 37; IMD37 616098   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Ears HP:0000388 (Otitis media), recurrent
Mouth Candida infections
Respiratory - HP:0002783 (Recurrent infections)
Abdomen Gastrointestinal Infectious HP:0002014 (Diarrhea)
Neurologic Central Nervous System HP:0002383 (Encephalitis)
Seizures
Immunology - HP:0002721 (Immunodeficiency)
Recurrent bacterial and viral infections
HP:0004313 (Hypogammaglobulinemia)
Decreased memory B cells
Decreased memory T cells
Increased percentage of naive B cells
Increased percentage of naive T cells
Miscellaneous - HP:0003593 (Onset in infancy)
 
BCOR 300485 MICROPHTHALMIA, SYNDROMIC 2; MCOPS2 300166   4 Inheritance - HP:0001423 (X-linked dominant)
Growth Height HP:0004322 (short stature)
Weight HP:0004325 (Low weight) (in some patients)
Other HP:0008897 (Postnatal growth retardation)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0000276 (Long face)
HP:0000343 (Long philtrum)
Ears HP:0000407 (sensorineural hearing loss)
HP:0000400 (Large ears)
Asymmetric ears
HP:0000358 (Posteriorly rotated ears)
Eyes HP:0000482 (Microcornea)
Congenital HP:0000518 (Cataracts)
HP:0000568 (Microphthalmia)
HP:0001126 (Cryptophthalmos)
HP:0000528 (Anophthalmia), clinical
Laterally curved eyebrows
HP:0000574 (Thick eyebrows)
HP:0000572 (Visual loss)
HP:0000501 (Glaucoma), secondary
HP:0000482 (Microcornea)
Persistent hyperplasia of primary vitreous
HP:0000508 (Ptosis)
HP:0000581 (Blepharophimosis)
HP:0000577 (Exotropia)
Iris synechia
HP:0000541 (Retinal detachment) (rare)
Phthisis bulbi (rare)
Nose HP:0000455 (Broad nasal tip)
HP:0000426 (High nasal bridge)
HP:0000456 (Bifid nasal tip)
Septate nasal cartilage
Mouth HP:0000175 (Cleft palate)
Submucous HP:0000175 (Cleft palate)
HP:0000193 (Bifid uvula)
Teeth Canine radiculomegaly
Delayed dentition
HP:0006335 (Persistent primary teeth)
HP:0000677 (Oligodontia)
HP:0000689 (Dental malocclusion)
HP:0011069 (Supernumerary teeth)
Fused teeth
Root dilacerations (extension)
Cardiovascular Heart HP:0001631 (Atrial septal defect)
HP:0001629 (Ventricular septal defect)
HP:0001634 (Mitral valve prolapse)
Tricuspid valve insufficiency
HP:0001650 (Aortic valve stenosis)
HP:0001642 (Pulmonary valve stenosis)
HP:0001643 (Patent ductus arteriosus)
Pentalogy of Fallot (rare)
Double-outlet right ventricle (rare)
HP:0001651 (Dextrocardia) (rare)
Abdomen External Features HP:0001537 (Umbilical hernia) (rare)
Gastrointestinal Atresia of ileum (rare)
Genitourinary External Genitalia (Male) HP:0000047 (Hypospadias) (rare)
Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
Internal Genitalia (Female) HP:0001153 (Septate vagina)
Kidneys Absent kidneys (rare)
Skeletal Skull HP:0000252 (microcephaly)
Spine HP:0002650 (Scoliosis) (in some patients)
Limbs Flexion HP:0004576 (large joint contractures) (in some patients)
Limited supination
HP:0002974 (Radioulnar synostosis)
Hands Clenched hands (rare)
Feet 2-3 toe HP:0006101 (Finger syndactyly)
Hammer toe (2-4 toes)
HP:0001762 ( Pes equinovarus) (rare)
Skin, Nails, Hair Hair Laterally curved eyebrows
HP:0000574 (Thick eyebrows)
Neurologic Central Nervous System HP:0001249 (Intellectual disability), mild
HP:0001270 (Delayed motor development)
Seizures (rare)
HP:0002313 (spastic paraparesis) (rare)
Hypoplastic or absent optic chiasm
HP:0002079 (Hypoplasia of corpus callosum) (rare)
Endocrine Features - HP:0000821 (Hypothyroidism) (rare)
Hypoadrenalism (rare)
 
BCS1L 603647 LEIGH SYNDROME; LS #256000   2 Inheritance - HP:0000007 (Autosomal recessive)
Mitochondrial
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Eyes HP:0000544 (Ophthalmoplegia)
HP:0000648 (optic atrophy)
HP:0000639 (Nystagmus)
HP:0000486 (Strabismus)
HP:0000508 (Ptosis)
HP:0000580 (Pigmentary retinopathy)
Respiratory - HP:0002793 (Abnormal respiratory patterns)
HP:0002878 (Respiratory failure)
Skin, Nails, Hair Hair HP:0000998 (hypertrichosis)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System HP:0001263 (global developmental delay)
HP:0008947 (Hypotonia, early)
HP:0001251 (ataxia)
HP:0007325 (generalized dystonia)
HP:0001260 (Dysarthria)
HP:0001257 (Spasticity)
HP:0001347 (Hyperreflexia)
Seizures
Brainstem abnormalities
HP:0001249 (Intellectual disability)
Lesions in basal ganglia, brainstem, cerebellum, thalamus, spinal cord characterized by HP:0007305 (CNS demyelination), necrosis, HP:0002171 (Gliosis), spongiosis, and capillary proliferation
Behavioral Psychiatric Manifestations HP:0000712 (Emotional lability)
Metabolic Features - HP:0003128 (Lactic acidosis)
Laboratory Abnormalities - HP:0002151 (Increased serum lactate)
HP:0002490 (Increased CSF lactate)
Miscellaneous - Onset usually in infancy or early childhood
HP:0003676 (Progressive disorder), usually with rapid, relentless course
Clinical heterogeneity
Genetic heterogeneity (may be caused by mutation in nuclear-encoded or mitochondrial-encoded genes)
Subset of patients have cytochrome c oxidase deficiency (see 220110)
See also X-linked Leigh syndrome (312170)
See also French-Canadian type of Leigh syndrome (220111)
Increased lactate (P, C)
BOLA3 613183 MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 2; MMDS2 614299   1 Inheritance - HP:0000007 (Autosomal recessive)
Cardiovascular Heart HP:0001644 (dilated cardiomyopathy)
Respiratory - HP:0002878 (Respiratory failure)
Abdomen Liver HP:0002240 (Hepatomegaly)
Gastrointestinal HP:0002013 (Vomiting)
Muscle, Soft Tissue - HP:0003324 (Muscle weakness)
Neurologic Central Nervous System Seizures
Epileptic HP:0004319 (nonprogressive encephalopathy)
HP:0001254 (Lethargy)
HP:0001263 (global developmental delay)
Metabolic Features - HP:0003128 (Lactic acidosis)
Laboratory Abnormalities - Increased serum and urinary lactate
Increased urinary 2-hydroxybutyrate
Increased serum glycine, leucine, isoleucine, valine
Decreased activity of pyruvate dehydrogenase complex
Decreased activity of 2-oxoacid dehydrogenases
Decreased activity of mitochondrial respiratory complexes
Miscellaneous - Onset soon after birth
HP:0001522 (Death in infancy)
 
BRAF 164757 CARDIOFACIOCUTANEOUS SYNDROME 1; CFC1 #115150   2 Inheritance - HP:0000006 (Autosomal dominant)
Growth Height HP:0004322 (short stature), postnatal
Other HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000256 (Macrocephaly), relative
HP:0000268 (Dolichocephaly)
Face HP:0011220 (Prominent forehead)
HP:0000341 (Bitemporal narrowing)
HP:0009891 (Hypoplastic orbital ridges)
HP:0002002 (Prominent philtrum)
HP:0000280 (Coarse facies)
HP:0000347 (Micrognathia)
Convex facial profile
Ears HP:0000358 (Posteriorly rotated ears)
HP:0000369 (Low-set ears)
HP:0009908 (Earlobe creases)
HP:0000410 (Hearing loss)
Eyes HP:0000508 (Ptosis)
HP:0000639 (Nystagmus)
HP:0000486 (Strabismus)
HP:0000494 (Downslanting palpebral fissures)
HP:0000316 (Hypertelorism)
HP:0000520 (Exophthalmos)
HP:0000286 (Epicanthus)
HP:0000545 (Myopia)
HP:0001093 (Optic nerve dysplasia)
HP:0000657 (Oculomotor apraxia)
HP:0000529 (progressive visual loss)
Absence of eyebrows
Absence of eyelashes
Nose Short HP:0000463 (Upturned nose)
HP:0000414 (Bulbous nasal tip)
HP:0005280 (depressed nasal bridge)
Mouth Submucous HP:0000175 (Cleft palate)
HP:0000218 (High-arched palate)
HP:0000194 (Open mouth)
HP:0100703 (Tongue thrusting)
Teeth HP:0000689 (Dental malocclusion)
HP:0010807 (Open bite)
Posterior crossbite
Cardiovascular Heart HP:0001631 (Atrial septal defect)s
HP:0001642 (Pulmonic valve stenosis)
HP:0001639 (hypertrophic cardiomyopathy)
Chest External Features HP:0000767 (HP:0000766 (Pectus deformities) excavatum)
HP:0000768 (Pectus carinatum)
Abdomen Spleen HP:0001744 (Splenomegaly)
Gastrointestinal HP:0011968 (feeding difficulties)
Dysmotility
HP:0002013 (Vomiting)
HP:0002019 (Constipation)
HP:0002020 (Gastroesophageal reflux)
Genitourinary Kidneys HP:0000126 (Hydronephrosis)
Skeletal - HP:0002761 (Generalized joint laxity)
HP:0002750 (Delayed bone age)
HP:0000938 (Osteopenia)
Hands HP:0001187 (Hyperextensible fingers)
HP:0004209 (Fifth finger clinodactyly)
Multiple palmar creases
Feet Multiple plantar creases
Skin, Nails, Hair Skin Severe atopic HP:0011123 (dermatitis)
HP:0008064 (ichthyosis)
HP:0007543 (epidermal hyperkeratosis) (especially extensor surfaces)
Cavernous HP:0001028 (Hemangioma)
Keratosis pilaris
Multiple palmar creases
HP:0001003 (Multiple lentigines)
Hair HP:0008070; Sparse, curly hair
Slow-growing hair
Absence of eyebrows
Absence of eyelashes
Neurologic Central Nervous System Mild to moderate HP:0001249 (Intellectual disability)
Seizures
HP:0008947 (Hypotonia, early)
HP:0001276 (Muscle hypertonia)
HP:0000238 (Hydrocephalus)
HP:0002120 (Cortical atrophy)
HP:0007333 (Hypoplasia of the frontal lobes)
HP:0007370; Hypoplasia or HP:0007370 (Aplasia/Hypoplasia of the corpus callosum)
HP:0007366 (Brain stem atrophy)
Peripheral Nervous System HP:0003477 (Peripheral axonal neuropathy) (uncommon)
Prenatal Manifestations Amniotic Fluid HP:0001561 (Polyhydramnios)
Delivery HP:0001622 (Premature delivery)
Miscellaneous - Most cases are HP:0003745 (sporadic)
Associated with advanced paternal age
HP:0000006 (Autosomal dominant) transmission has been rarely reported
Phenotypic similarities to Noonan syndrome (163950)
Phenotypic similarities to Costello syndrome (218040)
 
BRAT1 614506 RIGIDITY AND MULTIFOCAL SEIZURE SYNDROME, LETHAL NEONATAL; RMFSL #614498   1 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly) (-1.5 to 2 SD)
HP:0000252 (microcephaly), progressive
Face HP:0000347 (Micrognathia) (in some patients)
Eyes HP:0000648 (optic atrophy) (1 family)
Cardiovascular Heart HP:0001662 (Bradycardia)
Respiratory - HP:0002104 (Apnea)
Skeletal - Joint HP:0004576 (large joint contractures)
Skull HP:0005486; Small or absent fontanels
Depressed frontal bones
Overlapping cranial sutures
Neurologic Central Nervous System HP:0001263 (Lack of psychomotor development)
HP:0002063 (Rigidity), axial and limb
Scissoring
Lack of volitional movement
Seizures, continuous, refractory
HP:0002123 (Myoclonic seizures)
HP:0001347 (Hyperreflexia)
HP:0003487 (Extensor plantar responses)
HP:0002169 (Clonus)
HP:0001276 (Muscle hypertonia)
HP:0002459 (Dysautonomia)
High voltage spikes over the temporal and central regions seen on EEG
Suppression-burst pattern
Multifocal seizures
Background slowing
HP:0002529 (Neuronal loss) in the striatum, cerebral cortex, and cerebellum (in some patients)
AstroHP:0002171 (Gliosis) (in some patients)
Corticobasal degeneration (in some patients)
HP:0012448 (Delayed myelination) (in some patients)
Prenatal Manifestations Movement Episodic myoclonic spasms
Miscellaneous - Onset at or soon after birth
HP:0001522 (Death in infancy)
 
BSCL2 606158 ENCEPHALOPATHY, PROGRESSIVE, WITH OR WITHOUT LIPODYSTROPHY; PELD 615924   2 Inheritance - HP:0000007 (Autosomal recessive)
Abdomen Liver HP:0002240 (Hepatomegaly) (in some patients)
Muscle, Soft Tissue - Lipoatrophic appearance
Loss of subcutaneous and visceral adipose tissue, mild
Neurologic Central Nervous System HP:0004319 (nonprogressive encephalopathy), progressive
HP:0002376 (Psychomotor regress)
HP:0000750 (Language delay)
HP:0002371 (Loss of speech)
HP:0001268 (cognitive decline)
HP:0001251 (ataxia)
HP:0001257 (Spasticity)
HP:0001347 (Hyperreflexia)
HP:0030182 (Tetraparesis/tetraplegia)
HP:0001336 (myoclonus)
HP:0007325 (generalized dystonia)
HP:0002322 (Resting tremor)
HP:0007256 (Pyramidal tract signs)
Seizures
HP:0002283 (global brain atrophy)
Atrophy of the caudate
HP:0002529 (Neuronal loss)
AstroHP:0002171 (Gliosis)
Axonal spheroids
Behavioral Psychiatric Manifestations HP:0000752 (Hyperactivity)
Laboratory Abnormalities - HP:0002155 (Hypertriglyceridemia) (in some patients)
Miscellaneous - Onset of HP:0004319 (nonprogressive encephalopathy) between ages 2 and 3 years
HP:0003676 (Progressive disorder)
Death usually occurs in childhood
Lipodystrophic appearance may be mild or not present
Hyperinsulinemia
Hypertriglyceridemia
Decreased serum leptin
Increased liver enzymes
BTD 609019 BIOTINIDASE DEFICIENCY #253260   1 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Ears HP:0000407 (sensorineural hearing loss)
Eyes HP:0000509 (Conjunctivitis)
HP:0000648 (optic atrophy)
HP:0000572 (Visual loss)
Respiratory - HP:0002789 (Tachypnea)
HP:0002104 (Apnea)
Breathing problems
Abdomen Liver HP:0002240 (Hepatomegaly)
Spleen HP:0001744 (Splenomegaly)
Gastrointestinal HP:0011968 (feeding difficulties)
HP:0002013 (Vomiting)
HP:0002014 (Diarrhea)
Skin, Nails, Hair Skin Skin HP:0000988 (rash)
Seborrheic HP:0011123 (dermatitis)
Skin infections
Hair HP:0001596 (Alopecia)
Neurologic Central Nervous System Seizures
HP:0008947 (Hypotonia, early)
HP:0001251 (ataxia)
HP:0012758 (neurodevelopmental delay)
Diffuse HP:0002283 (global brain atrophy)
Diffuse HP:0001272 (Cerebellar atrophy)
HP:0001254 (Lethargy)
Metabolic Features - Metabolic HP:0001993 (ketoacidosis)
Organic aciduria
Laboratory Abnormalities - Organic aciduria (elevated beta-hydroxyisovalerate, lactate, beta-methylcrotonylglycine, beta-hydroxypropionate, methylcitrate)
Mild HP:0001987 (hyperammonemia)
Biotinidase deficiency
Miscellaneous - Age of onset usually 1 week to 2 years
Increased beta-hydroxyisovalerate, lactate, beta-methylcrotonylglycine, beta-hydroxypropionate, methylcitrate (U)
BUB1B 602860 MOSAIC VARIEGATED ANEUPLOIDY SYNDROME 1; MVA1 #257300   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Weight HP:0001518 (Small for gestational age)
HP:0004325 (Low weight)
Other HP:0008897 (Postnatal growth retardation), prenatal and postnatal
Head and Neck Head HP:0000252 (microcephaly), severe
HP:0000248 (Brachycephaly)
Face HP:0000348 (High forehead)
HP:0011800 (Midface hypoplasia)
HP:0000347 (Micrognathia)
HP:0000343 (Long philtrum)
Ears HP:0000369 (Low-set ears)
HP:0000358 (Posteriorly rotated ears)
Eyes HP:0000316 (Hypertelorism)
HP:0000582 (Upslanting palpebral fissures)
HP:0000286 (Epicanthus)
HP:0000518 (Cataracts)
HP:0000639 (Nystagmus)
Nose HP:0003196; Short, wide nose
HP:0005280 (depressed nasal bridge)
HP:0000463 (Anteverted nares)
Mouth HP:0000175 (Cleft palate)
Triangular shaped mouth
Neck HP:0000470 (Short neck)
Chest Ribs, Sternum, Clavicles and Scapulae HP:0000879 (Short sternum)
Abdomen Gastrointestinal HP:0011968 (feeding difficulties)
Genitourinary - HP:0000062 (Ambiguous genitalia)
External Genitalia (Male) HP:0000054 (Small penis)
HP:0000047 (Hypospadias)
HP:0000048 (Bifid scrotum)
Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
Kidneys HP:0000107 (Renal cysts)
Wilms tumor
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay), profound
HP:0001249 (Intellectual disability), profound
HP:0008947 (Hypotonia, early), generalized
HP:0002069 (Tonic-clonic seizures)
HP:0002123 (myoclonic seizures)
HP:0006872 (Cerebral hypoplasia)
Pachymacrogyria
Cerebral oligogyria
Hypodysplasia of the corpus callosum
HP:0001274 (agenesis of corpus callosum)
Posterior fossa malformations
HP:0001305 (Dandy-Walker malformation)
HP:0002119 (ventriculomegaly)
HP:0000238 (Hydrocephalus)
HP:0001321 (Cerebellar hypoplasia)
Immunology - HP:0005387 (combined immunodeficiency)
Neoplasia - Propensity to tumor development
Wilms tumor
Nephroblastoma
Rhabdomyosarcoma
Leukemia
Prenatal Manifestations Amniotic Fluid HP:0001562 (Oligohydramnios)
Delivery Premature labor
Laboratory Abnormalities - Mitotic lymphocyte and fibroblast cultures show mosaic variegated aneuploidy
More than 50% of mitotic cells show premature chromatid separation (PCS) affecting all chromosomes
Anaphase loss or nondisjunction with trisomies, tetrasomies, monosomies
Miscellaneous - HP:0003812 (Variable phenotype)
Heterozygous parents are phenotypically normal but their cells show premature chromatid separation trait (PCS, 176430)
 
C10orf2 606075 MITOCHONDRIAL DNA DEPLETION SYNDROME 7 (HEPATOCEREBRAL TYPE); MTDPS7 #271245   1 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Ears Deafness
Loss of vestibular caloric response
Eyes HP:0000544 (Ophthalmoplegia)
HP:0000639 (Nystagmus)
HP:0000496 (Oculomotor abnormalities)
HP:0000817 (Poor eye contact)
HP:0000648 (optic atrophy)
Abdomen Liver Mitochondrial DNA depletion
Genitourinary Internal Genitalia (Female) Hypergonadotrophic HP:0000815 (Hypogonadism) (in females in adolescence)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
HP:0003324 (Muscle weakness)
Decreased complex I activity (rare)
Neurologic Central Nervous System HP:0001251 (ataxia)
HP:0002312 (Clumsiness)
HP:0002505 (Progressive inability to walk)
HP:0002305 (Athetosis)
HP:0008947 (Hypotonia, early)
HP:0002076 (Migraine)s (onset in adolescence)
HP:0001328 (Specific learning disability)
HP:0001249 (Intellectual disability), mild to moderate
Epilepsy, refractory (onset in adolescence or young adulthood)
HP:0002133 (Status epilepticus)
HP:0012847 (Epilepsia partialis continua)
Epileptic HP:0004319 (nonprogressive encephalopathy)
HP:0001272 (Cerebellar atrophy)
HP:0007366 (Brainstem atrophy)
HP:0002120 (Cortical atrophy)
Mitochondrial DNA depletion in brain tissue
Decreased mitochondrial respiratory chain complex activity
Atrophy of the posterior columns and spinocerebellar tracts
Brain MRI shows lesions consistent with epileptic episodes
Stoke-like lesions
Peripheral Nervous System Loss of deep tendon reflexes
HP:0003390 (Sensory neuropathy)
Behavioral Psychiatric Manifestations Mood disorders
Uncontrolled rage
HP:0001262 (Somnolence)
HP:0000709 (Psychosis)
Endocrine Features - Hypergonadotrophic HP:0000815 (Hypogonadism) (in females in adolescence)
Laboratory Abnormalities - HP:0002910 (HP:0002910 (abnormal liver enzymes) tests) (rare)
Miscellaneous - Onset 6 to 18 months
Some features occur in adolescence, including HP:0002076 (Migraine), seizures, and HP:0000708 (Psychiatric disorder)s
Severe epilepsy may lead to early death
HP:0003676 (Progressive disorder)
Carrier frequency in Finland is 1 in 230
 
C12orf57 615140 TEMTAMY SYNDROME; TEMTYS #218340   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Face HP:0000276 (Long face)
HP:0000347 (Micrognathia)
HP:0002007 (Frontal bossing)
HP:0000343 (Long philtrum)
Ears HP:0000369 (Low-set ears)
HP:0000377 (Simple ears)
Lop ears
Eyes HP:0000316 (Hypertelorism)
'Key-hole' iris, retina, choroid HP:0000589 (coloboma)
HP:0000545 (Myopia)
HP:0001083 (Ectopia lentis) (upward)
HP:0000494 (Downslanting palpebral fissures)
HP:0002553 (Arched eyebrows)
Nose HP:0000444 (Beaked nose)
Teeth HP:0000678 (Dental crowding)
HP:0000685 (Hypoplasia of teeth)
Skeletal Pelvis HP:0002827 (Hip dislocations)
Limbs HP:0002857 (Genua valga)
Hands HP:0009803 (short fingers) (2nd-5th fingers)
Bulbous thumbs
Feet HP:0009803 (short fingers) (2nd-5th toes)
HP:0001763 (pes planus)
HP:0001762 ( Pes equinovarus)
Neurologic Central Nervous System Global HP:0012758 (neurodevelopmental delay)
HP:0001249 (Intellectual disability)
HP:0008947 (Hypotonia, early)
Seizures, early-onset
Corpus callosum abnormalities
HP:0001274 (agenesis of corpus callosum)
Reduced white matter
Thalamic hypoplasia
HP:0002119 (ventriculomegaly)
HP:0007375 (Abnormal septum pellucidum)
Behavioral Psychiatric Manifestations HP:0000729 (autistic behaviour)
Miscellaneous - HP:0003593 (Onset in infancy)
Skeletal and facial features are variable
 
CACNA1A 601011 Cognitive impairment, autism and epileptic encephalopathy with mild cerebellar symptoms #108500 25735478 2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Ears HP:0000360 (Tinnitus)
Eyes Ictal and interictal HP:0000651 (diplopia)
Suppression of vestibuloocular reflex
Saccadic smooth pursuit
Gaze-evoked HP:0000639 (Nystagmus)
Interictal downbeat HP:0000639 (Nystagmus)
Ocular abnormalities often persist between attacks
Neurologic Central Nervous System HP:0002131 (episodic ataxia)
Unsteadiness, episodic
HP:0002321 (Vertigo)
HP:0002486 (Myotonia)
HP:0001260 (Dysarthria)
HP:0002076 (Migraine)
HP:0003324 (Muscle weakness)
HP:0003401 (Paresthesia)s
Interictal downbeat HP:0000639 (Nystagmus)
Interictal vestibular dysfunction
Interictal HP:0007325 (generalized dystonia) may occur later in disease course
Interictal HP:0001251 (ataxia) may occur later in disease course
EEG with paroxysmal activity
HP:0006855 (Atrophy of cerebellar vermis)
Miscellaneous - Most common episodic HP:0001251 (ataxia) syndrome
Onset usually in childhood or adolescence
Onset may occur in adulthood
HP:0003829 (Incomplete penetrance)
Progressive HP:0001251 (ataxia)
Episodes last from several hours to days
Frequency of episodes ranges from several per week to several per year
Symptoms precipitated by sudden movement, stress, exertion, exercise, fatigue, caffeine, alcohol, cigarettes
Favorable response of episodic attacks to acetazolamide
Phenotypic overlap with FHM1 (141500) and SCA6 (183086)
 
CACNA1D 114206 PRIMARY ALDOSTERONISM, SEIZURES, AND NEUROLOGIC ABNORMALITIES; PASNA #615474   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Eyes Cortical HP:0000618 (Blindness) (in one patient)
Cardiovascular Heart HP:0001712 (Left ventricular hypertrophy)
HP:0200128 (biventricular hypertrophy) (in one patient)
HP:0001629 (Ventricular septal defect) (in one patient)
HP:0001655 (Patent foramen ovale) (in one patient)
Second-degree HP:0012722 (heart block) (in one patient)
Vascular HP:0000822 (Hypertension), neonatal
Pulmonary artery HP:0000822 (Hypertension) (in one patient)
Genitourinary Kidneys HP:0000787 (Nephrolithiasis) (in one patient)
Neurologic Central Nervous System Global HP:0012758 (neurodevelopmental delay)
HP:0002069 (Tonic-clonic seizures)
HP:0002123 (myoclonic seizures)
Seizures, complex partial
HP:0100021 (cerebral palsy)
Spastic HP:0002445 (quadriplegia) (in one patient)
HP:0002305 (Athetosis), mild (in one patient)
Peripheral Nervous System HP:0100022 (Movement disorder)
Behavioral Psychiatric Manifestations Verbal outbursts (in one patient)
Metabolic Features - HP:0200114 (Metabolic alkalosis)
Endocrine Features - Elevated aldosterone
High aldosterone/renin ratio
Low plasma renin activity
Laboratory Abnormalities - HP:0002900 (Hypokalemia)
 
CACNA1E 601013 epilepsy   26795593 2 0  
CAD 114010 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Iz; CDG1Z #616457   2 Inheritance - HP:0000007 (Autosomal recessive)
Abdomen Gastrointestinal Pan-disaccharidase deficiency
Genitourinary Kidneys HP:0001947 (Renal tubular acidosis)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
HP:0008947 (Hypotonia, early)
HP:0002136 (Wide-based gait)
Seizures
Hematology - Anisopoikilocytosis
Acanthocytosis
Schistocytosis
Dyserythropoietic bone marrow biopsy
Laboratory Abnormalities - HP:0001987 (hyperammonemia), mild
Red blood cell proteins show abnormal glycosylation
Serum transferrin glycosylation is normal
Miscellaneous - HP:0003593 (Onset in infancy)
Serum transferrin glycosylation is normal
CALM1 114180     23388215 3 Inheritance - HP:0000006 (Autosomal dominant)
Cardiovascular Heart Recurrent episodes of HP:0001663 (ventricular fibrillation)
HP:0004751 (Paroxysmal ventricular tachycardia) , nonsustained (in some patients)
Syncopal episodes (in some patients)
Cardiac arrest (in some patients)
HP:0001699 (Sudden death) (in some patients)
HP:0005184 (Prolonged QTc interval) on electrocardiogram (ECG)
T-wave alternans on ECG (in some patients)
Atrioventricular block, 2:1, on ECG (in some patients)
Torsade de pointes on ECG (in some patients)
Miscellaneous - Some patients have HP:0003577 (Onset at birth) or in early infancy, whereas other have onset in late childhood or adolescence
Some patients experience neurologic sequelae (seizures
HP:0012758 (neurodevelopmental delay) after multiple episodes of cardiac arrest
In some patients, QTc interval is prolonged only during exercise testing
 
CARS2 612800 COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 27; COXPD27 616672   1 Inheritance -
HP:0000007 (Autosomal recessive)
Growth Other
HP:0001508 (Failure to thrive)
Head and Neck Head
HP:0000252 (microcephaly), postnatal
Ears
Hearing impairment, progressive
Eyes
HP:0000505 (Visual impairment), progressive
HP:0010553 (Oculogyric crisis)
No purposeful eye movements
Abdomen Liver
Combined mitochondrial respiratory chain deficiency
Microvesicular HP:0001397 (Liver steatosis)
Gastrointestinal
HP:0011968 (feeding difficulties)
Muscle, Soft Tissue -
HP:0008947 (Hypotonia, early), severe
Lack of antigravity movements
Decreased mitochondrial respiratory chain enzyme activity
Neurologic Central Nervous System
HP:0001263 (Delayed psychomotor development)
HP:0001268 (Cognitive decline)ion, associated with infections
HP:0001268 (cognitive decline), progressive, onset in childhood
HP:0030182 (Tetraparesis/tetraplegia), progressive
HP:0002123 (Myoclonic seizures)
HP:0001336 (myoclonus)
Intractable seizures
HP:0002133 (Status epilepticus)
Epileptic HP:0004319 (nonprogressive encephalopathy)
HP:0002179 (Opisthotonus)
HP:0002072 (Chorea)
HP:0007325 (generalized dystonia)
Background slowing seen on EEG
Multifocal epileptiform discharges seen on EEG
HP:0002283 (global brain atrophy)
HP:0002500 (White matter abnormalities)
HP:0002079 (Thin corpus callosum)
HP:0001321 (Cerebellar hypoplasia) (patient B
Peripheral Nervous System
HP:0001284 (Areflexia)
Laboratory Abnormalities -
HP:0002151 (Increased serum lactate) (in some patients)
Increased lactate (P)
CASK 300172 MENTAL RETARDATION AND MICROCEPHALY WITH PONTINE AND CEREBELLAR HYPOPLASIA; MICPCH #300749   2 Inheritance - HP:0001423 (X-linked dominant)
Growth Height HP:0004322 (short stature)
Weight HP:0004325 (Low weight)
Other HP:0008897 (Postnatal growth retardation), postnatal
Head and Neck Head HP:0000252 (microcephaly), progressive (-3.5 to -10 SD)
Face Oval face
HP:0000343 (Long philtrum)
HP:0000347 (Micrognathia)
Ears HP:0000400 (macrotia)
HP:0000407 (Sensorineural hearing loss) (less common)
Eyes HP:0001090 (Large eyes)
HP:0000316 (Hypertelorism), mild
HP:0000286 (Epicanthus)
HP:0000609 (Optic nerve hypoplasia) (less common)
HP:0000543 (Optic disc pallor) (less common)
HP:0000486 (Strabismus) (less common)
HP:0000639 (Nystagmus) (less common)
Nose HP:0007965 (Broad nasal bridge)
HP:0000426 (Prominent nasal bridge)
HP:0000455 (Broad nasal tip)
HP:0003196 (Small nose)
Mouth HP:0000218 (High-arched palate)
Skeletal Spine HP:0002650 (Scoliosis) (less common) SKIN, HAIR, NAILS :
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
HP:0003324 (Muscle weakness)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
HP:0001249 (Intellectual disability), moderate to severe
Most never acquire independent ambulation
HP:0001344 (absent speech) development
Axial HP:0008947 (Hypotonia, early)
Peripheral HP:0001276 (Muscle hypertonia)
HP:0001257 (Spasticity)
HP:0001347 (Hyperreflexia)
Seizures (less common)
Hyposensitivity to pain (less common)
Proportionate pontoHP:0001321 (Cerebellar hypoplasia) seen on MRI
Dilated fourth ventricle
Simplified gyration in the frontal cortex (less common)
Miscellaneous - HP:0003577 (Onset at birth) or early infancy
HP:0001999 (Dysmorphic facial features) are variable
 
CASQ2 114251 VENTRICULAR TACHYCARDIA, CATECHOLAMINERGIC POLYMORPHIC, 2; CPVT2 611938   2 Inheritance - HP:0000007 (Autosomal recessive)
Cardiovascular Heart Polymorphic HP:0004751 (Paroxysmal ventricular tachycardia) induced by physical activity, stress, or catecholamine infusion
HP:0001662 (Bradycardia), relative resting
HP:0001279 (Syncope)
HP:0001699 (Sudden death)
Neurologic Central Nervous System Seizures
 
CBS 613381 HOMOCYSTINURIA DUE TO CYSTATHIONINE BETA-SYNTHASE DEFICIENCY #236200   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height Normal to HP:0000098 (Tall stature)
Other Occasional HP:0001508 (Failure to thrive) in infancy
Head and Neck Eyes HP:0001083 (Ectopia lentis)
HP:0000545 (Myopia)
HP:0000501 (Glaucoma)
Mouth HP:0000218 (High-arched palate)
Teeth HP:0000678 (Crowded teeth)
Cardiovascular Heart HP:0001658 (Myocardial infarction)
HP:0001634 (Mitral valve prolapse)
Chest Ribs, Sternum, Clavicles and Scapulae HP:0000767 (HP:0000766 (Pectus deformities) excavatum)
HP:0000768 (Pectus carinatum)
Abdomen External Features HP:0000023 (Inguinal hernia)
Liver Fatty changes in liver
Pancreas HP:0001733 (Pancreatitis)
Skeletal - Generalized HP:0000939 (Osteoporosis)
Spine Biconcave 'codfish' vertebrae
HP:0002751 (kyphoscoliosis)
Limbs Dolichostenomelia
HP:0001166 (Arachnodactyly)
Limited joint mobility
Skin, Nails, Hair Skin HP:0007513 (Generalized hypopigmentation)
Malar flush
HP:0000965 (Livedo reticularis)
Hair HP:0007513 (Generalized hypopigmentation)
Fine, HP:0002299 (brittle hair)
Neurologic Central Nervous System Seizures
HP:0001249 (Intellectual disability)
Cerebrovascular accident
Behavioral Psychiatric Manifestations HP:0000708 (Psychiatric disorder)s
HP:0000716 (Depression)
HP:0012075 (Personality disorder)
Hematology - Thromboembolism (25%)
Laboratory Abnormalities - Homocystinuria
Methioninuria
Cystathionine beta-synthase deficiency
Miscellaneous - Fifty-percent of individuals responsive to pyridoxine (vitamin B6)
Pyridoxine responsive individuals often have milder manifestations than those not responsive
Management of homocystinuria includes low methionine, cystine supplemented diet for pyridoxine nonresponders and pyridoxine supplementation for pyridoxine responders
Treatment with betaine, especially for pyridoxine nonresponders
Thromboembolism is the most common cause of death
Frequency between 1 in 58,000 to 1 in 1,000,000
Homocystinuria
Methioninuria
CC2D2A 612013 JOUBERT SYNDROME 9; JBTS9 #612285   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes HP:0000510 (Retinitis pigmentosa)
HP:0000483 (Astigmatism)
HP:0000639 (Nystagmus)
HP:0000518 (Cataracts)
Neurologic Central Nervous System HP:0001249 (Intellectual disability), mild to moderate
Seizures (in some patients)
HP:0002119 (ventriculomegaly)
HP:0002419 (Molar tooth sign)
 
CCBE1 612753 HENNEKAM LYMPHANGIECTASIA-LYMPHEDEMA SYNDROME 1; HKLLS1 235510   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0008897 (Postnatal growth retardation), mild
Head and Neck Face HP:0001004; Lymphedematous facies
HP:0012368 (Flat face)
HP:0000278 (Retrognathia)
HP:0000337 (Broad forehead)
HP:0000319 (smooth philtrum)
Ears HP:0000407 (sensorineural hearing loss)
HP:0000405 (Conductive hearing loss)
HP:0000369 (Low-set ears)
Eyes Periorbital HP:0000969 (Edema)
HP:0000316 (Hypertelorism)
HP:0000286 (Epicanthus)
HP:0000501 (Glaucoma)
Nose Flat, HP:0007965 (Broad nasal bridge)
Mouth HP:0000160 (small mouth)
HP:0000189 (Narrow palate)
HP:0000212 (Gingival hypertrophy)
Teeth HP:0000677 (Oligodontia)
Peg-shaped incisors
Delayed eruption
Cardiovascular Heart HP:0001631 (Atrial septal defect)
HP:0001629 (Ventricular septal defect)
HP:0005183 (Pericardial lymphangiectasia)
HP:0001698 (Pericardial effusion)s
Respiratory Lung HP:0006531 (Pleural lymphangiectasia)
Pleural effusions
Chest Ribs, Sternum, Clavicles and Scapulae Horizontal clavicles
HP:0000767 (HP:0000766 (Pectus deformities) excavatum)
Abdomen Gastrointestinal Intestinal lymphangiectasia
Protein-losing enteropathy
Rectal prolapse
HP:0001537 (Umbilical hernia)
Genitourinary Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
Kidneys HP:0000126 (Hydronephrosis)
Renal lymphangiectasia
HP:0000085 (Horseshoe kidney)
HP:0000086 (Renal ectopia)
Ureters Duplicated ureter
HP:0000076 (Vesicoureteral reflux)
Skeletal - HP:0002750 (Delayed bone age)
Skull Coronal HP:0011324 (multisutural craniosynostosis)
Spine HP:0002650 (Scoliosis)
HP:0002414 (Spina bifida) occulta
Pelvis HP:0002866 (Hypoplastic iliac wings)
Hands Cutaneous HP:0006101 (Finger syndactyly) (fingers 2,3,4,5)
HP:0100490 (Camptodactyly)
Bilateral HP:0000954 (Single transverse palmar crease)
HP:0200055 (Small hands)
Feet HP:0001762 ( Pes equinovarus)
HP:0001773 (Small feet)
Skin, Nails, Hair Skin Bilateral HP:0000954 (Single transverse palmar crease)
Erysipelas
Hair HP:0001007 (Hirsutism)
Muscle, Soft Tissue - HP:0001004 (Lymphedema) (lower extremities)
Neurologic Central Nervous System HP:0001249 (Intellectual disability) (sometimes)
Focal parietal HP:0001302 (pachygyria)
Seizures
Behavioral Psychiatric Manifestations HP:0000752 (Hyperactivity)
Endocrine Features - Thyroid lymphangiectasia
Immunology - Hypoglobulinemia
Laboratory Abnormalities - HP:0003073 (Hypoalbuminemia)
 
CCDC88C 611204 HYDROCEPHALUS, NONSYNDROMIC, AUTOSOMAL RECESSIVE 1; HYC1 #236600   2 Inheritance - HP:0000007 (Autosomal recessive)
Neurologic Central Nervous System HP:0000238 (Hydrocephalus)
HP:0002119 (ventriculomegaly)
HP:0001249 (Intellectual disability)
HP:0001270 (Delayed motor development)
Seizures
Miscellaneous - HP:0003577 (prenatal onset)
 
CCM2 607929 CEREBRAL CAVERNOUS MALFORMATIONS 2; CCM2 #603284   2 Inheritance - HP:0000006 (Autosomal dominant)
Skin, Nails, Hair Skin Palmar HP:0001009 (Telangiectasia) (described in 1 family)
Neurologic Central Nervous System Cerebral cavernous malformations
Seizures
Recurrent headaches
Hemorrhagic HP:0001297 (stroke)
Miscellaneous - Genetic heterogeneity (see 116800 for summary)
HP:0003745 (sporadic) cases often single lesions versus multiple lesions in familial cases
 
CD96 606037 C SYNDROME 211750   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Other HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000243 (Trigonocephaly)
HP:0000252 (microcephaly)
Face HP:0000347 (Micrognathia)
Ears HP:0000369 (Low-set ears)
HP:0000358 (Posteriorly rotated ears)
Eyes HP:0000286 (Epicanthus)
HP:0000582 (Upward slanting palpebral fissures)
HP:0000486 (Strabismus)
Nose HP:0000463 (Anteverted nares)
HP:0007965 (Broad nasal bridge)
HP:0003196 (Short nose)
Mouth HP:0000218 (High-arched palate)
HP:0000190 (Abnormal oral frenula)
HP:0009100 (Thick anterior alveolar ridges)
HP:0000154 (wide mouth)
Cardiovascular Heart HP:0001629 (Ventricular septal defect)
Vascular HP:0001643 (Patent ductus arteriosus)
Chest Ribs, Sternum, Clavicles and Scapulae HP:0000766 (HP:0000766 (Pectus deformities) deformities)
Anomalous ribs
Fused sternal ossification centers
Abdomen External Features HP:0001539 (Omphalocele)
Liver HP:0002240 (Hepatomegaly)
Genitourinary External Genitalia (Female) HP:0000057 (Clitoromegaly)
Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
Kidneys Renal cortical cysts
Skeletal - HP:0002750 (Delayed bone age)
Spine HP:0002650 (Scoliosis)
Pelvis HP:0002827 (Hip dislocations)
Limbs HP:0009826 (Short limbs)
HP:0003083 (Radial head dislocations)
Hands HP:0001162 (Postaxial hand polydactyly)
HP:0004209 (Fifth finger clinodactyly)
Ulnar deviation of the fingers
Terminal transverse limb reduction
Metacarpal hypoplasia
HP:0001830 (Postaxial feet polydactyly)
HP:0006101 (Finger syndactyly)
Terminal transverse limb reduction
Skin, Nails, Hair Skin HP:0000973 (Skin laxity)
Neurologic Central Nervous System HP:0008947 (Hypotonia, early)
Seizures
HP:0001263 (global developmental delay)
 
CDC42 116952 TAKENOUCHI-KOSAKI SYNDROME; TKS 26795593 616737 26795593 2 0  
CDK5 123831 LISSENCEPHALY 7 WITH CEREBELLAR HYPOPLASIA; LIS7 616342   1 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0000350 (Small forehead)
HP:0000293 (Full cheeks)
HP:0000347 (Micrognathia)
Mouth Downslanting corners of the mouth
Neck HP:0000470 (Short neck)
Respiratory - Shallow breathing
Skeletal - HP:0002804 (HP:0002804 (Arthrogryposis) multiplex)
Hands Clenched hands
Skin, Nails, Hair Hair Low hairline
HP:0001007 (Hirsutism)
Muscle, Soft Tissue - HP:0001004 (Lymphedema)
Nonspecific myopathic changes seen on muscle biopsy
Increased internal nuclei
Small round skeletal muscle fibers
Neurologic Central Nervous System HP:0001263 (Lack of psychomotor development)
Seizures, intractable
Burst-suppression pattern seen on EEG
HP:0001339 (Lissencephaly)
HP:0001339 (Agyria)
HP:0001321 (Cerebellar hypoplasia)
HP:0001274 (agenesis of corpus callosum)
Disorganized cortical lamination
Peripheral Nervous System HP:0001284 (Areflexia)
Decreased pain response
Miscellaneous - HP:0003577 (Onset at birth)
Death in first days or months of life
 
CDK5RAP2 608201 MICROCEPHALY 3, PRIMARY, AUTOSOMAL RECESSIVE; MCPH3 #604804   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly), severe (-4 to -8 SDS)
HP:0000340 (Sloping forehead)
Ears HP:0000407 (sensorineural hearing loss) (in some patients)
Eyes HP:0000520 (Prominent eyes) (in one patient)
Teeth Conical-shaped teeth (in one patient)
Neurologic Central Nervous System HP:0001249 (Intellectual disability), mild to moderate
HP:0012758 (neurodevelopmental delay)
Small but structurally normal cerebral cortex
HP:0009879 (Simplified gyral pattern) (in one patient)
Small frontal lobes (in one patient)
Partial HP:0007370 (Aplasia/Hypoplasia of the corpus callosum) (in one patient)
Tonic clonic seizures, infrequent (in one patient)
 
CDKL5 300203 EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2; EIEE2 #300672   1 Inheritance - HP:0001423 (X-linked dominant)
Head and Neck Head HP:0000252 (microcephaly), progressive
Face HP:0000337 (Broad forehead)
HP:0011220 (Prominent forehead)
Eyes HP:0000490 (Deep-set eyes)
Large-appearing eyes
Well-defined eyebrows
Nose HP:0000463 (Anteverted nares)
Mouth HP:0012471 (full lips)
Respiratory - Breath-holding episodes
HP:0002883 (Hyperventilation)
Abdomen Gastrointestinal HP:0002019 (Constipation)
HP:0002020 (Gastroesophageal reflux)
Skeletal Spine HP:0002650 (Scoliosis)
Hands HP:0200055 (Small hands)
HP:0001182 (tapered fingers)
Feet HP:0001773 (Small feet)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System Seizures, infantile-onset
HP:0012469 (Infantile spasms)
Multifocal seizures
Generalized seizures
HP:0002069 (Tonic-clonic seizures)
HP:0002123 (Myoclonic seizures)
HP:0002521 (hypsarrhythmia)
HP:0001263 (Delayed psychomotor development)
HP:0002376 (Psychomotor regress)may occur
HP:0001249 (Intellectual disability), profound
HP:0001344 (absent speech) development
HP:0000817 (Poor eye contact)
Motor HP:0011098 (Speech apraxia)
HP:0008947 (Hypotonia, early)
HP:0001336 (myoclonus)
HP:0002540 (inability to walk) independently
EEG abnormalities
Sleep difficulties
HP:0002459 (Dysautonomia)s
Behavioral Psychiatric Manifestations HP:0000729 (autistic behaviour)
HP:0000733 (Stereotypic behavior)
Hand-wringing
Breath-holding episodes
Miscellaneous - HP:0003593 (Onset in infancy)
Seizures are usually refractory
Females are most often affected, but rare male cases have been reported
Males are more severely affected
HP:0001999 (Dysmorphic facial features) are subtle
Some phenotypic overlap with Rett syndrome (312750)
 
CECR1 607575 SNEDDON SYNDROME 182410   3 Inheritance - HP:0000007 (Autosomal recessive)
Cardiovascular Vascular Cerebrovascular ischemic attacks
Cerebrovascular hemorrhagic attacks
HP:0000822 (Hypertension)
Skin, Nails, Hair Skin Livedo racemosa (usually on trunk and/or lower extremities)
Erythematous, irregular netlike pattern of vessels
Skin Histology Intimal proliferation of small arteries
Occlusion of small arteries
Neurologic Central Nervous System Cerebrovascular ischemic attacks, transient (proceed secondary neurologic findings)
Headaches
Visual changes
HP:0002301 (Hemiplegia)
HP:0001260 (Dysarthria)
HP:0010628 (Facial palsy)
Seizures
HP:0002322 (Resting tremor)
HP:0001268 (cognitive decline)
Laboratory Abnormalities - Associated with serum anti-phospholipid antibodies in about 50% of patients
Miscellaneous - Incidence of 4 per million per year
Secondary features include arterial HP:0000822 (Hypertension) and renal involvement
Women are more often affected
Onset in young adulthood
HP:0003676 (Progressive disorder)
 
CENPE 117143 MICROCEPHALY 13, PRIMARY, AUTOSOMAL RECESSIVE; MCPH13 616051   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature) (in 1 of 2 sibs)
Weight HP:0004325 (Low weight) due to HP:0001510 (Growth delay)
Other HP:0001511 (Intrauterine growth retardation) (IUGR)
Head and Neck Head HP:0000252 (microcephaly) (-7 to -9 SD)
Face HP:0000340 (Sloping forehead)
HP:0000350 (Small forehead)
HP:0000311 (Round face)
HP:0000347 (Micrognathia)
Ears Large appearing ears
Eyes HP:0000639 (Nystagmus), intermittent (1 of 2 sibs)
Nose HP:0000448 (Large nose)
Cardiovascular Heart Congenital HP:0001723 (restrictive cardiomyopathy) (in 1 of 2 sibs)
Chest Ribs, Sternum, Clavicles and Scapulae Widening of the ribs, mild (in 1 of 2 sibs)
Skeletal Limbs Metaphyseal sclerosis, mild (in 1 of 2 sibs)
Hands HP:0200055 (Small hands)
Feet HP:0001773 (Small feet)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development), moderate to severe
Seizures (in 1 of 2 sibs)
HP:0009879 (Simplified gyral pattern) (in 1 of 2 sibs)
Partial HP:0001274 (agenesis of corpus callosum) (in 1 of 2 sibs)
HP:0001321 (Cerebellar hypoplasia) (in 1 of 2 sibs)
 
CEP164 614848 NEPHRONOPHTHISIS 15; NPHP15 614845   4 Inheritance - HP:0000007 (Autosomal recessive)
Growth Weight HP:0001513 (Obesity) (in some patients)
Head and Neck Eyes HP:0000546 (Retinal degeneration)
Leber congenital HP:0007875 (Congenital amaurosis)
HP:0000639 (Nystagmus) (in 1 patient)
HP:0000618 (Blindness) (in some patients)
Abdomen Liver HP:0001399 (Liver failure) (in some patients)
Genitourinary Kidneys HP:0000090 (Nephronophthisis)
Skeletal Hands Polydactyly (in 1 patient)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay) (in 1 patient)
Seizures (in 1 patient)
HP:0006817 (Aplasia/Hypoplasia of the cerebellar vermis) (in 1 patient)
HP:0003812 (Variable phenotype)
 
CERS1 606919 EPILEPSY, PROGRESSIVE MYOCLONIC, 8; EPM8 #616230   2 Inheritance - HP:0000007 (Autosomal recessive)
Neurologic Central Nervous System HP:0001336 (myoclonus), action
Generalized HP:0002069 (Tonic-clonic seizures)
HP:0100543 (Cognitive impairment)
HP:0001249 (Intellectual disability)
HP:0000726 (Dementia)
HP:0001272; Cerebellar andHP:0007366 (Brainstem atrophy), mild
Miscellaneous - Onset between 6 and 16 years of age
HP:0003676 (Progressive disorder)
Some patients may become wheelchair-bound
0
CHD2 602119 EPILEPTIC ENCEPHALOPATHY, CHILDHOOD-ONSET; EEOC 615369   1 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Eyes HP:0000992 (Photosensitivity) (in some patients)
Neurologic Central Nervous System Epileptic HP:0004319 (nonprogressive encephalopathy)
HP:0001263 (Delayed psychomotor development)
Seizures
HP:0002123 (Myoclonic seizures)
HP:0010819 (atonic seizures)
HP:0002373 (febrile seizures)
HP:0002121 (Absence seizures)
HP:0002069 (Tonic-clonic seizures)
HP:0002133 (Status epilepticus)
HP:0002376 (Psychomotor regress)
HP:0001249 (Intellectual disability)
Abnormal EEG
Behavioral Psychiatric Manifestations HP:0000729 (autistic behaviour) (rare)
Miscellaneous - Onset between ages 1 to 3 years
Patients can have multiple seizure types
All reported cases have occurred de novo
 
CHKB 612395 MUSCULAR DYSTROPHY, CONGENITAL, MEGACONIAL TYPE; MDCMC 602541   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly)
Face Facial HP:0003324 (Muscle weakness)
Cardiovascular Heart HP:0001644 (dilated cardiomyopathy) (occurs in about 50%)
Skin, Nails, Hair Skin HP:0008064 (ichthyosis)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early), neonatal
HP:0003324 (Muscle weakness)
HP:0003560 (Muscular dystrophy)
HP:0003391 (Gowers sign)
Muscle biopsy shows necrotic and regenerating fibers
Mitochondrial enlargement
Mitochondria are placed at the periphery of muscle fibers
Variation in fiber size
Neurologic Central Nervous System HP:0001249 (Intellectual disability)
HP:0001270 (Delayed motor development)
HP:0002515 (Waddling gait)
Some patients never achieve independent ambulation
HP:0001249 (Intellectual disability)
HP:0000750 (language delay)
Seizures (3 patients)
Laboratory Abnormalities - HP:0003236 (Increased serum creatine kinase)
Miscellaneous - HP:0003577 (Onset at birth)
Slowly progressive
Some patients may die from HP:0001638 (Cardiomyopathy) in the first or second decade of life
 
CHRNA2 118502 EPILEPSY, NOCTURNAL FRONTAL LOBE, 4; ENFL4 610353   2 Inheritance - HP:0000006 (Autosomal dominant)
Neurologic Central Nervous System Seizures, nocturnal, usually occur in daily clusters
Sudden awakening
Unintelligible speech, vocalizations, grunting
Fearful expression
Frightening sensation
Tingling sensation
Shivering sensation
Complex motor behavior such as sleep walking
Hypermotor behavior
Tongue movements, protrusions
EEG shows frontal lobe origin
Miscellaneous - Genetic heterogeneity (see ENFL1, 600513)
Onset in childhood (mean age 10 years)
May be misdiagnosed as nightmares, night terrors, parasomnias, or HP:0000708 (Psychiatric disorder)s
Frequency and severity of seizures tends to decrease with age
 
CHRNA4 118504 EPILEPSY, NOCTURNAL FRONTAL LOBE, 1; ENFL1 600513   2 Inheritance - HP:0000006 (Autosomal dominant)
Neurologic Central Nervous System Motor seizures, nocturnal, usually occur in clusters (up to 8 per night) during dozing or on awakening
Arm flexion
Tonic head extension
Unintelligible speech
Mouth movements
HP:0011157 (Auras) may occur
Ictal EEG showed partial seizures with frontal lobe origin
HP:0001249 (Intellectual disability) (rare)
Miscellaneous - Onset in childhood
May be misdiagnosed as nightmares, night terrors, parasomnias, or HP:0000708 (Psychiatric disorder)s
HP:0003829 (Incomplete penetrance)
 
CHRNB2 118507 EPILEPSY, NOCTURNAL FRONTAL LOBE, 3; ENFL3 #605375   2 0  
CLDN16 603959 HYPOMAGNESEMIA 3, RENAL; HOMG3 248250   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Eyes HP:0000486 (Strabismus)
HP:0000639 (Nystagmus)
HP:0000540 (Hypermetropia)
HP:0000545 (Myopia)
HP:0000483 (Astigmatism)
Abdomen Gastrointestinal HP:0002027 (Abdominal pain)
HP:0011968 (feeding difficulties)
Genitourinary Kidneys HP:0000103 (Polyuria)
HP:0000121 (Nephrocalcinosis)
Progressive HP:0000083 (renal insufficiency)
HP:0000083 (Renal failure)
HP:0000787 (Nephrolithiasis)
HP:0005567 (Renal magnesium wasting)
Renal calcium wasting
Bladder Recurrent urinary tract infections
Muscle, Soft Tissue - HP:0001281 (Tetany)
Neurologic Central Nervous System Seizures
Metabolic Features - HP:0001959 (Polydipsia)
Incomplete distal HP:0001947 (Renal tubular acidosis)
Laboratory Abnormalities - HP:0002917 (Hypomagnesemia)
Normal serum calcium
Elevated parathyroid hormone
HP:0002149 (Hyperuricemia)
Hypermagnesiuria
HP:0002150 (Hypercalciuria)
Hypocitraturia
Hematuria
Abacterial leukocyturia
Miscellaneous - Onset in early childhood
Presenting symptoms - recurrent UTI, HP:0000103 (Polyuria)/HP:0001959 (Polydipsia), hematuria, and abacterial leukocyturia
HP:0002150 (Hypercalciuria) and/or HP:0000787 (Nephrolithiasis) occurs in heterozygotes
 
CLIC2 300138 MENTAL RETARDATION, X-LINKED, SYNDROMIC 32; MRXS32 300886   2 Inheritance - HP:0001419 (X-linked recessive)
Head and Neck Ears HP:0000400 (macrotia)
Cardiovascular Heart HP:0001640 (Cardiomegaly)
HP:0001635 (Congestive heart failure)
Valvular insufficiency
Atrial flutter (rare)
Genitourinary External Genitalia (Male) HP:0000053 (Macroorchidism)
Skeletal Spine HP:0002751 (kyphoscoliosis) (rare)
Limbs HP:0004576 (large joint contractures) of the large joints
Hands Abnormal positioning of the thumbs
Neurologic Central Nervous System Global HP:0012758 (neurodevelopmental delay)
HP:0001249 (Intellectual disability), profound
HP:0001344 (absent speech)
Seizures
HP:0001257 (Spasticity) (rare)
HP:0000238 (Hydrocephalus) (rare)
Female carriers may show mild HP:0001328 (Learning disabilities)
 
CLN3 607042 CEROID LIPOFUSCINOSIS, NEURONAL, 3; CLN3 #204200   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes HP:0000572 (Visual loss), progressive (4 to 10 years)
HP:0000618 (Blindness) (6 to 14 years)
HP:0000510 (Retinitis pigmentosa)
HP:0000608 (Macular degeneration)
HP:0000648 (optic atrophy)
Abolished electroretinogram (ERG)
Cardiovascular Heart Concentric HP:0001639 (hypertrophic cardiomyopathy), severe (later onset in protracted cases)
Muscle, Soft Tissue - Autophagic vacuoles seen on biopsy (in some patients)
Intermyofibrillar and subsarcolemmal accumulation of electron-dense material (in some patients)
Neurologic Central Nervous System HP:0002361 (Psychomotor deterioration)
HP:0001249 (Intellectual disability)
HP:0000726 (Dementia)
HP:0002071 (extrapyramidal signs)
HP:0001336 (myoclonus)
HP:0001300 (Parkinsonism)
HP:0001317 (Cerebellar signs)
Progressive HP:0002540 (inability to walk)
Seizures
HP:0001260 (Dysarthria)
Autofluorescent lipopigment in neurons
HP:0002283 (global brain atrophy)
Behavioral Psychiatric Manifestations Difficulty in school
Behavioral changes
Mood disturbances
HP:0000739 (Anxiety)
HP:0000709 (Psychosis)
Hematology - HP:0001922 (Vacuolated lymphocytes)
Laboratory Abnormalities - Lipopigment in extraneuronal cells
'Fingerprint profiles' ultrastructurally in cells
'Curvilinear profiles' ultrastructurally in cells
Miscellaneous - Onset at 4 to 10 years
Death at 20 to 40 years
HP:0003828 (Variable severity), some patients have a protracted course with little neurologic involvement
1.02 kb genomic deletion in 85% of Batten disease alleles worldwide
Fingerprint profiles' ultrastructurally in cells
'Curvilinear profiles' ultrastructurally in cells
CLN5 608102 CEROID LIPOFUSCINOSIS, NEURONAL, 5; CLN5 #256731   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes HP:0000572 (Visual loss), progressive
HP:0000546 (Retinal degeneration)
HP:0000639 (Nystagmus) (1 family)
Neurologic Central Nervous System HP:0002312 (Clumsiness)
HP:0002333 (Motor deterioration)
HP:0002376 (Psychomotor regression)
HP:0001251 (ataxia)
HP:0001260 (Dysarthria) (1 family)
HP:0001310 (Dysmetria) (1 family)
HP:0002075 (Dysdiadochokinesis) (1 family)
Seizures
HP:0001336 (myoclonus)
HP:0001249 (Intellectual disability)
HP:0100543 (Cognitive impairment) (1 family)
Neurophysiologic abnormalities (EEG, VEP, SEP)
Characteristic findings on MRI
Autofluorescent lipopigment in neurons
HP:0001272 (Cerebellar atrophy) (1 family)
Behavioral Psychiatric Manifestations Concentration difficulties
Laboratory Abnormalities - 'Fingerprint' profiles ultrastructurally
'Curvilinear' profiles ultrastructurally
'Rectilinear' profiles ultrastructurally
Miscellaneous - Onset at 4 to 7 years
Later onset can also occur (up to age 17 years)
Death at 13 to 30 years
Fingerprint' profiles ultrastructurally
'Curvilinear' profiles ultrastructurally
'Rectilinear' profiles ultrastructurally
CLN6 606725 CEROID LIPOFUSCINOSIS, NEURONAL, 4A, AUTOSOMAL RECESSIVE; CLN4A #601780   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes HP:0000572 (Visual loss), progressive
HP:0000546 (Retinal degeneration)
Neurologic Central Nervous System Seizures
HP:0002333 (Motor deterioration)
HP:0001268 (cognitive decline)
Neurophysiologic abnormalities (EEG, SEP, VEP)
Autofluorescent lipopigment in neurons
Laboratory Abnormalities - 'Curvilinear' profiles ultrastructurally
'Fingerprint' profiles ultrastructurally
Miscellaneous - Onset 5 to 7 years
Death in the mid-twenties
Fingerprint' profiles ultrastructurally
'Curvilinear' profiles ultrastructurally
'Rectilinear' profiles ultrastructurally
CLN8 607837 CEROID LIPOFUSCINOSIS, NEURONAL, 8, NORTHERN EPILEPSY VARIANT #610003   2 Inheritance - HP:0000007 (Autosomal recessive)
Neurologic Central Nervous System Seizures, onset age 5 to 10 years
Generalized HP:0002069 (Tonic-clonic seizures)
Complex partial seizures
EEG abnormalities
HP:0001268 (cognitive decline) beginning 2 to 5 years after onset of seizures
HP:0001249 (Intellectual disability) by age 30 years
HP:0002312 (Clumsiness)
Difficulties with equilibrium
HP:0002283 (global brain atrophy), progressive
HP:0001272 (Cerebellar atrophy), progressive
Autofluorescent lipopigment in neurons
Behavioral Psychiatric ManifestationsHP:0000737 (Irritability) beginning at puberty
Inattentiveness
HP:0000711 (Restlessness)
Laboratory Abnormalities - Intracellular curvilinear profiles on ultrastructural analysis
Intracellular granular material on ultrastructural analysis
Miscellaneous - Onset age 5 to 10 years
Decrease in seizure frequency in middle age
Slowly progressive
Protracted disease course
Allelic disorder to CLN8 (600143)
All known cases are caused by a Finnish founder mutation in the CLN8 gene (607837.0001)
Intracellular curvilinear profiles ultrastructurally in cells
Intracellular granular material ultrastructurally in cells
CLP1 608757 PONTOCEREBELLAR HYPOPLASIA, TYPE 10; PCH10 #615803   1 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001510 (Growth delay)
Head and Neck Head HP:0000252 (microcephaly), progressive
Eyes HP:0000520 (Prominent eyes)
HP:0000637 (Long palpebral fissures)
High-HP:0002553 (Arched eyebrows)
HP:0000527 (Long eyelashes)
HP:0000817 (Poor eye contact)
HP:0000565 (Esotropia)
HP:0000486 (Strabismus)
HP:0000639 (Nystagmus)
Nose HP:0000431 (Broad nasal bridge)
HP:0000430 (Hypoplastic nasal alae) nasi
HP:0003196 (Short nose)
Mouth HP:0000219 (Thin upper lip)
HP:0000218 (High-arched palate)
Genitourinary Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development), profound
HP:0004319 (nonprogressive encephalopathy)
Lack of independent sitting or walking
Seizures, intractable
HP:0001344 (absent speech)
HP:0001276 (Muscle hypertonia)
HP:0001257 (Spasticity)
HP:0001347 (Hyperreflexia)
HP:0002079 (Thin corpus callosum)
PontoHP:0001321 (Cerebellar hypoplasia)
HP:0002539 (Cortical dysplasia)
HP:0009879 (Simplified gyral pattern)
HP:0002120 (Cortical atrophy)
HP:0002500 (White matter abnormalities)
HP:0002119 (ventriculomegaly)
HP:0012448 (Delayed myelination)
Peripheral Nervous System Axonal HP:0007141 (Sensorimotor neuropathy)
Miscellaneous - HP:0003577 (Onset at birth)
Severe phenotype
Founder effect in Turkish families
 
CLPB 616254 3-METHYLGLUTACONIC ACIDURIA WITH CATARACTS, NEUROLOGIC INVOLVEMENT, AND NEUTROPENIA; MEGCANN 616271   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001510 (Growth delay)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0001999 (Dysmorphic facial features) (in some patients)
Eyes HP:0000518 (Cataracts) (in most patients)
Abdomen Gastrointestinal HP:0011968 (feeding difficulties)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early), neonatal
HP:0001276 (Hypertonicity), neonatal (in severely affected patients)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development) (in most patients)
HP:0001249 (Intellectual disability)
HP:0002376 (Psychomotor regression) (in some patients)
HP:0001257 (Spasticity)
HP:0007256 (Pyramidal tract signs)
HP:0002071 (extrapyramidal signs)
HP:0100022 (Movement disorder)
Seizures (in some patients)
HP:0001272 (Cerebellar atrophy)
HP:0002283 (global brain atrophy)
Atrophy of the basal ganglia
Immunology - HP:0001875 (Neutropenia) (in most patients)
Bone marrow shows deficient granulopoiesis
HP:0002783 (Recurrent infections) (in some patients)
Laboratory Abnormalities - Increased urinary 2-methylglutaconic acid
Miscellaneous - HP:0003577 (Onset at birth)
HP:0003577 (prenatal onset) in severely affected patients
HP:0003812 (Variable phenotype)
HP:0003676 (Progressive disorder)
Death often in childhood
Increased 2-methylglutaconic acid (U)
CLPP 601119 PERRAULT SYNDROME 3; PRLTS3 #614129   4 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature) (in some patients)
Head and Neck Head HP:0000252 (microcephaly) (in some patients)
EarsHP:0000410 (Hearing loss, mixed), congenital sensorineural, severe to profound
Genitourinary Internal Genitalia (Female)
Small ovaries
Streak ovaries
HP:0000013 (Rudimentary uterus)
Neurologic Central Nervous System Seizures (in some patients)
Learning and HP:0012758 (neurodevelopmental delay) (in some patients)
cerebellar HP:0001251 (ataxia) (in some patients)
Endocrine Features - Increased gonadotropin levels (in female patients)
 
CLTC 118955 Epilepsy   26795593 2 0  
CNKSR2 300724 X-linked intellectual disability and seizures   25223753 2 0  
CNNM2 607803 HYPOMAGNESEMIA, SEIZURES, AND MENTAL RETARDATION; HOMGSMR #616418   1 Inheritance - HP:0000006 (Autosomal dominant)
HP:0000007 (Autosomal recessive) (1 family)
Head and Neck Head HP:0000252 (microcephaly) (1 family)
Genitourinary Kidneys Urinary magnesium wasting
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
HP:0001249 (Intellectual disability)
Poor or HP:0001344 (absent speech)
Seizures
Reduced myelination
Failure of opercularization
Increased cerebrospinal fluid spaces
Laboratory Abnormalities - Low serum magnesium
Miscellaneous - De novo mutation in heterozygotes
Onset in the first year of life
Seizures may be refractory to treatment
Patients with recessive mutations have a more severe phenotype
 
CNTN2 190197 EPILEPSY, FAMILIAL ADULT MYOCLONIC, 5; FAME5 #615400   2 Inheritance - HP:0000007 (Autosomal recessive)
Neurologic Central Nervous System HP:0002123 (myoclonic seizures)
Seizures, focal
Generalized HP:0002069 (Tonic-clonic seizures)(GTCS)
Auditory, olfactory, and visual HP:0011157 (Auras)
Cortical myoclonic HP:0002322 (Resting tremor)s characterized by 8 to 10-Hz discharges
Temporal epileptiform discharges seen on EEG
Head nodding
Borderline intelligence
Mesial temporal sclerosis (in 1 patient)
Behavioral Psychiatric Manifestations Depressive symptoms
Onset in the second decade
HP:0002322 (Resting tremor)s develop after seizures
Good seizure control with medication
 
CNTNAP2 604569 CORTICAL DYSPLASIA-FOCAL EPILEPSY SYNDROME; CDFES 610042   2 0  
COG4 606976 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIj; CDG2J 613489   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0001999 (Dysmorphic features)
Eyes HP:0000639 (Nystagmus)
Respiratory - HP:0002205 (Recurrent respiratory infections)
Abdomen Liver HP:0002240 (Hepatomegaly)
HP:0001399 (Liver failure)
HP:0001394 (liver cirrhosis)
Spleen HP:0001744 (Splenomegaly)
Gastrointestinal HP:0011968 (feeding difficulties)
Recurrent HP:0002014 (Diarrhea)
HP:0004798 (Recurrent gastrointestinal infections)
Skin, Nails, Hair Hair HP:0100874 (Thick hair)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development), moderate to severe
HP:0001344 (absent speech)
Axial HP:0008947 (Hypotonia, early)
Peripheral HP:0001276 (Muscle hypertonia)
HP:0001251 (ataxia)
HP:0002311 (Incoordination)
Seizures
HP:0002283 (global brain atrophy)
HP:0002079 (Thin corpus callosum)
Behavioral Psychiatric ManifestationsHP:0000737 (Irritability)
Hematology - Decreased coagulation factors
Laboratory Abnormalities - Serum transferrin isoelectric focusing shows type 2 pattern
Sialylation defects
Galactosylation defects
Impaired N-glycosylation
Impaired O-glycosylation
Some fragmented or disrupted Golgi
HP:0002910 (HP:0002910 (abnormal liver enzymes) tests)
Increased alkaline phosphatase
Isoelectric focusing of serum transferrin (type II)
COG6 606977 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIl; CDG2L 614576   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0000278 (Retrognathia)
Eyes Broad palpebral fissures
Abdomen Liver HP:0002240 (Hepatomegaly)
Micronodular HP:0001394 (liver cirrhosis)
Macrovesicular HP:0001397 (Liver steatosis)
Gastrointestinal HP:0001545 (Anteriorly placed anus)
HP:0002014 (Diarrhea), recurrent
HP:0002037 (Inflammatory bowel disease)
Genitourinary Kidneys HP:0000114 (Proximal tubulopathy)
Skeletal Hands HP:0001162 (Postaxial hand polydactyly)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development), mild
Axial HP:0008947 (Hypotonia, early)
Seizures
Loss of consciousness
HP:0002170 (Intracranial hemorrhage)ing
Hematology - Bleeding due to vitamin K deficiency
Immunology - Primary HP:0005387 (combined immunodeficiency)
HP:0002783 (Recurrent infections)
HP:0004313 (Hypogammaglobulinemia)
T-cell dysfunction
Granulocyte dysfunction
Laboratory Abnormalities - Abnormal isoelectric focusing of serum transferrin (type 2 pattern)
HP:0002910 (HP:0002910 (abnormal liver enzymes) tests)
Miscellaneous - HP:0003577 (Onset at birth)
HP:0001522 (Death in infancy)
Primary combined immunodeficiency
Isoelectric focusing of serum transferrin (type II)
COG7 606978 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIe; CDG2E #608779   2 0 Isoelectric focusing of serum transferrin (type II)
COG8 606979 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIh; CDG2H 611182   2 0 Isoelectric focusing of APOC-III
COL18A1 120328 KNOBLOCH SYNDROME 1; KNO1 #267750   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes High HP:0000545 (Myopia)
VitreoHP:0000546 (Retinal degeneration)
HP:0000541 (Retinal detachment) (childhood)
Congenital HP:0000518 (Cataracts)
Syneresis
Vitreous attachment at the disc
Persistent fetal hyaloid vasculature
Peripapillary atrophy
Phthisis bulbi
Band keratopathy
HP:0001104 (Macular hypoplasia)
Irregular white dots at the vitreoretinal interface
HP:0000572 (Visual loss)
HP:0000639 (Nystagmus)
Skeletal Skull Midline occipital bone defect
Skin, Nails, Hair Hair HP:0001596 (Alopecia) at the occipital defect
Neurologic Central Nervous System Occipital HP:0002084 (Encephalocele)
Occipital dermal sinus tract
HP:0001268 (cognitive decline) (in some patients)
cerebellar HP:0001251 (ataxia), adult-onset (in 1 family)
Seizures
HP:0002119 (Ventriculomegaly)
Subependymal heterotopic nodules
HP:0002126 (Polymicrogyria)
HP:0001272 (Cerebellar atrophy) (in 1 family)
HP:0002283 (global brain atrophy) (in 1 family)
Miscellaneous - Phenotypic variability
 
COL4A1 120130 BRAIN SMALL VESSEL DISEASE WITH OR WITHOUT OCULAR ANOMALIES; BSVD #607595   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Eyes Retinal arteriolar tortuosity
HP:0007513 (Generalized hypopigmentation) of the fundus
Scotomas, episodic
Blurred vision, episodic
HP:0000483 (Astigmatism) (in some patients)
Amblyopia (reported in 1 family)
HP:0000486 (Strabismus)
HP:0000545 (Myopia)
HP:0000540 (Hypermetropia) (in some patients)
HP:0007663 (Decreased visual acuity) (rare)
Congenital HP:0000518 (Cataracts) (in some patients)
High intraocular pressure
HP:0000501 (Glaucoma) (rare)
HP:0000568 (Microphthalmia) (in some patients)
HP:0000482 (Microcornea) (in some patients)
HP:0007957 (Corneal opacity) (in some patients)
Corneal neovascularization (rare)
Axenfeld-Rieger anomalies (in some patients)
HP:0007676 (Iris hypoplasia) (in some patients)
Corectopia (in some patients)
HP:0011500 (Polycoria) (rare)
Iridogoniodysgenesis (rare)
Iridocorneal synechiae (in some patients) Prominent or irregular HP:0007873 (Schwalbe line) (in some patients)
Macular hemorrhage and Fuchs spots (rare)
Peripapillary atrophy (rare)
Choroidal atrophy (rare)
Neurologic Central Nervous System HP:0002076 (Migraine) with or without HP:0011157 (Auras)
Infantile HP:0001269 (Hemiparesis)
Central HP:0010628 (Facial palsy) (in some patients)
HP:0002132 (Porencephaly) (in some patients)
Seizures (in some patients)
HP:0001249 (Intellectual disability), mild (in some patients)
Diffuse periventricular HP:0002352 (leukoencephalopathy)
White matter hyperintensities (MRI, T2 images) suggestive of old infarcts
Deep hypointensities (MRI, T2) suggestive of past microbleeds
Dilated perivascular spaces
Miscellaneous - Variable age of onset (range 4 months to 45 years)
A subset of patients may have congenital abnormalities of the ocular anterior segment
 
COL4A2 120090 PORENCEPHALY 2; POREN2 614483   2 Inheritance - HP:0000006 (Autosomal dominant)
Neurologic Central Nervous System HP:0002132 (Porencephaly)
HP:0002119 (ventriculomegaly)
HP:0002170 (Intracranial hemorrhage)
HP:0002301 (Hemiplegia)
HP:0001257 (Spasticity)
HP:0001263 (Delayed psychomotor development)
Seizures
Reduced white matter volume
Structural brain anomalies
Miscellaneous - HP:0003828 (Variable severity)
HP:0003829 (Incomplete penetrance)
 
COL4A3BP 604677 MENTAL RETARDATION, AUTOSOMAL DOMINANT 34; MRD34 616351   2 0  
COQ2 609825 COENZYME Q10 DEFICIENCY, PRIMARY, 1; COQ10D1 #607426   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Ears HP:0000408 (sensorineural hearing loss)
Eyes HP:0000639 (Nystagmus)
HP:0000572 (Visual loss)
HP:0000510 (Retinitis pigmentosa)
Cardiovascular Heart HP:0001639 (hypertrophic cardiomyopathy)
Abdomen Liver HP:0001399 (Liver failure)
Genitourinary Kidneys HP:0000100 (Nephrotic syndrome)
HP:0000096 (Glomerulosclerosis)
Podocyte effacement
HP:0012103 (Abnormality of the mitochondrion) in podocytes
Muscle, Soft Tissue - HP:0003324 (Muscle weakness), progressive
Exertional fatigue
Lipid accumulation
Decreased coenzyme Q10 content
HP:0003200 (Ragged red fibers)
Neurologic Central Nervous System HP:0004319 (nonprogressive encephalopathy)
Seizures
HP:0001249 (Intellectual disability)
cerebellar HP:0001251 (ataxia)
HP:0001272 (Cerebellar atrophy)
Metabolic Features - HP:0003128 (Lactic acidosis)
Hematology - HP:0001903 (Anemia)
HP:0001876 (Pancytopenia)
Laboratory Abnormalities - Decreased levels of coenzyme Q10 in skeletal muscle (5-35%)
Decreased activity of coenzyme Q10-dependent respiratory chain complexes
HP:0003236 (Increased serum creatine kinase)
Miscellaneous - HP:0003812 (Variable phenotype)
Onset usually in infancy or early childhood
Some patients may show a favorable response to oral Coenzyme Q10 supplementation
Lactic acidosis
COQ4 612898 COENZYME Q10 DEFICIENCY, PRIMARY, 5; COQ10D5 #616276   1 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001511 (Intrauterine growth retardation) (in some patients)
Cardiovascular Heart HP:0001662 (Bradycardia) (in some patients)
HP:0001639 (hypertrophic cardiomyopathy) (in some patients)
Left ventricular hyperplasia (in some patients)
HP:0001643 (Patent ductus arteriosus) (in some patients)
Respiratory - HP:0002093 (Respiratory insufficiency), neonatal
Abdomen Gastrointestinal HP:0002015 (Swallowing difficulties)
Skeletal Spine HP:0002650 (Scoliosis) MUSCLE : HP:0008947 (Hypotonia, early), neonatal
Skeletal muscle biopsy shows decreased activity of coupled complex activity in the electron transport chain
Increased activity of coupled complex activity in the electron transport chain
Decreased coenzyme Q10 levels
Neurologic Central Nervous System Epileptic HP:0004319 (nonprogressive encephalopathy) (in some patients)
Regression of psychomotor development
HP:0002505 (Progressive inability to walk)
Seizures (in some patients)
HP:0001321 (Cerebellar hypoplasia) (in some patients)
Peripheral Nervous System Sensorimotor HP:0001271 (polyneuropathy)
Laboratory Abnormalities - HP:0002151 (Increased serum lactate)
Increased urinary 2-OH glutaric acid (in some patients)
Miscellaneous - HP:0003577 (Prenatal onset) or HP:0003577 (Onset at birth)
Most patients die in the first days of life
Increased lactate (P)
Increased 2-OH glutaric acid (U)
COQ6 614647 COENZYME Q10 DEFICIENCY, PRIMARY, 6; COQ10D6 #614650   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Ears HP:0000407 (Sensorineural hearing loss)
Genitourinary Kidneys HP:0000100 (Nephrotic syndrome)
Focal segmental HP:0000096 (Glomerulosclerosis)
Diffuse HP:0001967 (mesangial sclerosis) (less common)
HP:0000093 (Proteinuria)
Neurologic Central Nervous System Seizures (uncommon)
Laboratory Abnormalities - HP:0000093 (Proteinuria)
Miscellaneous - HP:0003593 (Onset in infancy)
Rapidly progressive
Death in childhood may occur due to end-stage renal disease
Treatment with oral coenzyme Q may ameliorate symptoms
 
COQ9 612837 COENZYME Q10 DEFICIENCY, PRIMARY, 5; COQ10D5 #614654   1 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly), postnatal
Cardiovascular Heart HP:0001712 (Left ventricular hypertrophy)
Abdomen Gastrointestinal HP:0011968 (feeding difficulties)
Genitourinary Kidneys HP:0000114 (Proximal renal tubulopathy)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Decreased coenzyme Q10
Decreased activity of complexes II+III
Neurologic Central Nervous System Global HP:0012758 (neurodevelopmental delay)
Seizures, refractory
HP:0001276 (Muscle hypertonia), peripheral HP:0007325 (generalized dystonia)
Poor responsiveness
HP:0002283 (global brain atrophy)
HP:0001272 (Cerebellar atrophy)
Peripheral Nervous System HP:0001347 (Hyperreflexia)
Voice - HP:0001612 (Weak cry)
Metabolic Features - HP:0003128 (Lactic acidosis)
Laboratory Abnormalities - HP:0002151 (Increased serum lactate)
Lactic acidosis
COX10 602125 MITOCHONDRIAL COMPLEX IV DEFICIENCY 256000   2 Inheritance - HP:0000007 (Autosomal recessive)
Mitochondrial
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Ears HP:0000407 (sensorineural hearing loss)
Eyes HP:0000648 (optic atrophy)
HP:0000580 (Pigmentary retinopathy)
HP:0000508 (Ptosis)
Cardiovascular Heart HP:0001639 (hypertrophic cardiomyopathy)
Respiratory - HP:0002880 (Respiratory difficulties)
HP:0002878 (Respiratory failure) due to HP:0003324 (Muscle weakness)
Exertional HP:0002094 (dyspnea)
Abdomen Liver HP:0001410 (Liver dysfunction)
HP:0002240 (Hepatomegaly)
Liver biopsy shows increased lipid droplets and HP:0012103 (Abnormality of the mitochondrion)
Genitourinary Kidneys HP:0001994 (Renal Fanconi syndrome)
HP:0000124 (Renal tubular dysfunction)
Biopsy shows decreased cytochrome c oxidase
Muscle, Soft Tissue - HP:0003324 (Muscle weakness)
HP:0008947 (Hypotonia, early)
HP:0003546 (Exercise intolerance)
Muscle biopsy shows decrease or absence of cytochrome c oxidase
Increased lipid droplets and HP:0012103 (Abnormality of the mitochondrion)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
HP:0001270 (Delayed motor development)
HP:0008947 (Hypotonia, early)
HP:0001251 (ataxia)
HP:0007256 (pyramidal tract signs)
Seizures
HP:0001249 (Intellectual disability)
HP:0002490 (Increased CSF lactate)
Symmetric lesions in the basal ganglia consistent with Leigh syndrome (256000), in a subset of patients
Metabolic Features - HP:0003128 (Lactic acidosis)
Hematology - HP:0001903 (Anemia) (associated with mutation in the COX10 gene)
Laboratory Abnormalities - HP:0002151 (Increased serum lactate)
HP:0002490 (Increased CSF lactate)
HP:0000093 (Proteinuria)
HP:0003076 (Glucosuria)
HP:0003355 (Aminoaciduria)
HP:0003109 (Hyperphosphaturia)
Decreased activity of cytochrome c oxidase in muscle and fibroblasts
Miscellaneous - Marked clinical heterogeneity
Symptom onset ranges from infancy to adulthood
Death may occur in infancy
Genetic heterogeneity (may be caused by mutation in nuclear-encoded or mitochondrial-encoded genes)
Subset of patients have Leigh syndrome (256000)
Subset of patients have French-Canadian Leigh syndrome (220111)
Increased lactate (P, C)
COX14 614478 MITOCHONDRIAL COMPLEX IV DEFICIENCY 220110   2 Inheritance - HP:0000007 (Autosomal recessive)
Mitochondrial
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Ears HP:0000407 (sensorineural hearing loss)
Eyes HP:0000648 (optic atrophy)
HP:0000580 (Pigmentary retinopathy)
HP:0000508 (Ptosis)
Cardiovascular Heart HP:0001639 (hypertrophic cardiomyopathy)
Respiratory - HP:0002880 (Respiratory difficulties)
HP:0002878 (Respiratory failure) due to HP:0003324 (Muscle weakness)
Exertional HP:0002094 (dyspnea)
Abdomen Liver HP:0001410 (Liver dysfunction)
HP:0002240 (Hepatomegaly)
Liver biopsy shows increased lipid droplets and HP:0012103 (Abnormality of the mitochondrion)
Genitourinary Kidneys HP:0001994 (Renal Fanconi syndrome)
HP:0000124 (Renal tubular dysfunction)
Biopsy shows decreased cytochrome c oxidase
Muscle, Soft Tissue - HP:0003324 (Muscle weakness)
HP:0008947 (Hypotonia, early)
HP:0003546 (Exercise intolerance)
Muscle biopsy shows decrease or absence of cytochrome c oxidase
Increased lipid droplets and HP:0012103 (Abnormality of the mitochondrion)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
HP:0001270 (Delayed motor development)
HP:0008947 (Hypotonia, early)
HP:0001251 (ataxia)
HP:0007256 (pyramidal tract signs)
Seizures
HP:0001249 (Intellectual disability)
HP:0002490 (Increased CSF lactate)
Symmetric lesions in the basal ganglia consistent with Leigh syndrome (256000), in a subset of patients
Metabolic Features - HP:0003128 (Lactic acidosis)
Hematology - HP:0001903 (Anemia) (associated with mutation in the COX10 gene)
Laboratory Abnormalities - HP:0002151 (Increased serum lactate)
HP:0002490 (Increased CSF lactate)
HP:0000093 (Proteinuria)
HP:0003076 (Glucosuria)
HP:0003355 (Aminoaciduria)
HP:0003109 (Hyperphosphaturia)
Decreased activity of cytochrome c oxidase in muscle and fibroblasts
Miscellaneous - Marked clinical heterogeneity
Symptom onset ranges from infancy to adulthood
Death may occur in infancy
Genetic heterogeneity (may be caused by mutation in nuclear-encoded or mitochondrial-encoded genes)
Subset of patients have Leigh syndrome (256000)
Subset of patients have French-Canadian Leigh syndrome (220111)
Increased lactate (P, C)
COX15 603646 CARDIOENCEPHALOMYOPATHY, FATAL INFANTILE, DUE TO CYTOCHROME c OXIDASE DEFICIENCY 2; CEMCOX2 #615119   1 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly)
Cardiovascular Heart HP:0001639 (hypertrophic cardiomyopathy), biventricular
Glycogen deposition
Markedly decreased cytochrome c oxidase activity
Abdomen Liver HP:0001397 (Liver steatosis)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Increased intermyofibrillar and subsarcolemmal glycogen
Mildly decreased cytochrome c oxidase activity
Neurologic Central Nervous System HP:0004319 (nonprogressive encephalopathy)
HP:0002171 (Gliosis)
Metabolic Features - HP:0003128 (Lactic acidosis), persistent
Prenatal Manifestations Movement HP:0001558 (Decreased fetal movement)
Lactic acidosis
COX20 614698 MITOCHONDRIAL COMPLEX IV DEFICIENCY 220110   2 Inheritance - HP:0000007 (Autosomal recessive)
Mitochondrial
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Ears HP:0000407 (sensorineural hearing loss)
Eyes HP:0000648 (optic atrophy)
HP:0000580 (Pigmentary retinopathy)
HP:0000508 (Ptosis)
Cardiovascular Heart HP:0001639 (hypertrophic cardiomyopathy)
Respiratory - HP:0002880 (Respiratory difficulties)
HP:0002878 (Respiratory failure) due to HP:0003324 (Muscle weakness)
Exertional HP:0002094 (dyspnea)
Abdomen Liver HP:0001410 (Liver dysfunction)
HP:0002240 (Hepatomegaly)
Liver biopsy shows increased lipid droplets and HP:0012103 (Abnormality of the mitochondrion)
Genitourinary Kidneys HP:0001994 (Renal Fanconi syndrome)
HP:0000124 (Renal tubular dysfunction)
Biopsy shows decreased cytochrome c oxidase
Muscle, Soft Tissue - HP:0003324 (Muscle weakness)
HP:0008947 (Hypotonia, early)
HP:0003546 (Exercise intolerance)
Muscle biopsy shows decrease or absence of cytochrome c oxidase
Increased lipid droplets and HP:0012103 (Abnormality of the mitochondrion)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
HP:0001270 (Delayed motor development)
HP:0008947 (Hypotonia, early)
HP:0001251 (ataxia)
HP:0007256 (pyramidal tract signs)
Seizures
HP:0001249 (Intellectual disability)
HP:0002490 (Increased CSF lactate)
Symmetric lesions in the basal ganglia consistent with Leigh syndrome (256000), in a subset of patients
Metabolic Features - HP:0003128 (Lactic acidosis)
Hematology - HP:0001903 (Anemia) (associated with mutation in the COX10 gene)
Laboratory Abnormalities - HP:0002151 (Increased serum lactate)
HP:0002490 (Increased CSF lactate)
HP:0000093 (Proteinuria)
HP:0003076 (Glucosuria)
HP:0003355 (Aminoaciduria)
HP:0003109 (Hyperphosphaturia)
Decreased activity of cytochrome c oxidase in muscle and fibroblasts
Miscellaneous - Marked clinical heterogeneity
Symptom onset ranges from infancy to adulthood
Death may occur in infancy
Genetic heterogeneity (may be caused by mutation in nuclear-encoded or mitochondrial-encoded genes)
Subset of patients have Leigh syndrome (256000)
Subset of patients have French-Canadian Leigh syndrome (220111)
Increased lactate (P, C)
COX6B1 124089 MITOCHONDRIAL COMPLEX IV DEFICIENCY 220110   2 Inheritance - HP:0000007 (Autosomal recessive)
Mitochondrial
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Ears HP:0000407 (sensorineural hearing loss)
Eyes HP:0000648 (optic atrophy)
HP:0000580 (Pigmentary retinopathy)
HP:0000508 (Ptosis)
Cardiovascular Heart HP:0001639 (hypertrophic cardiomyopathy)
Respiratory - HP:0002880 (Respiratory difficulties)
HP:0002878 (Respiratory failure) due to HP:0003324 (Muscle weakness)
Exertional HP:0002094 (dyspnea)
Abdomen Liver HP:0001410 (Liver dysfunction)
HP:0002240 (Hepatomegaly)
Liver biopsy shows increased lipid droplets and HP:0012103 (Abnormality of the mitochondrion)
Genitourinary Kidneys HP:0001994 (Renal Fanconi syndrome)
HP:0000124 (Renal tubular dysfunction)
Biopsy shows decreased cytochrome c oxidase
Muscle, Soft Tissue - HP:0003324 (Muscle weakness)
HP:0008947 (Hypotonia, early)
HP:0003546 (Exercise intolerance)
Muscle biopsy shows decrease or absence of cytochrome c oxidase
Increased lipid droplets and HP:0012103 (Abnormality of the mitochondrion)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
HP:0001270 (Delayed motor development)
HP:0008947 (Hypotonia, early)
HP:0001251 (ataxia)
HP:0007256 (pyramidal tract signs)
Seizures
HP:0001249 (Intellectual disability)
HP:0002490 (Increased CSF lactate)
Symmetric lesions in the basal ganglia consistent with Leigh syndrome (256000), in a subset of patients
Metabolic Features - HP:0003128 (Lactic acidosis)
Hematology - HP:0001903 (Anemia) (associated with mutation in the COX10 gene)
Laboratory Abnormalities - HP:0002151 (Increased serum lactate)
HP:0002490 (Increased CSF lactate)
HP:0000093 (Proteinuria)
HP:0003076 (Glucosuria)
HP:0003355 (Aminoaciduria)
HP:0003109 (Hyperphosphaturia)
Decreased activity of cytochrome c oxidase in muscle and fibroblasts
Miscellaneous - Marked clinical heterogeneity
Symptom onset ranges from infancy to adulthood
Death may occur in infancy
Genetic heterogeneity (may be caused by mutation in nuclear-encoded or mitochondrial-encoded genes)
Subset of patients have Leigh syndrome (256000)
Subset of patients have French-Canadian Leigh syndrome (220111)
Increased lactate (P, C)
COX8A 123870 CYTOCHROME c OXIDASE, SUBUNIT 8A; COX8A 220110       Increased lactate (P, C)
CPA6 609562 EPILEPSY, FAMILIAL TEMPORAL LOBE, 5; ETL5 #614417   2 Inheritance - HP:0000006 (Autosomal dominant)
Neurologic Central Nervous System Seizures, temporal lobe
Structural changes in the temporal lobe
Miscellaneous - Variable age of onset
 
CPOX 612732 COPROPORPHYRIA, HEREDITARY; HCP 121300   3 Inheritance - HP:0000006 (Autosomal dominant)
Cardiovascular Heart HP:0001649 (Tachycardia) (hereditary coproporphyria, HCP)
Vascular HP:0000822 (Hypertension) (HCP)
Respiratory Lung HP:0002203 (Respiratory paralysis) (HCP)
Abdomen Liver HP:0002240 (Hepatomegaly) (harderoporphyria)
Spleen HP:0001744 (Splenomegaly) (harderoporphyria)
Gastrointestinal HP:0002027 (Abdominal pain) (HCP)
Severe HP:0002019 (Constipation)
HP:0002013 (Vomiting) (HCP)
HP:0002014 (Diarrhea) (HCP)
Skin, Nails, Hair Skin HP:0000992 (Photosensitivity) (harderoporphyria and HCP)
HP:0000952 (Jaundice) (harderoporphyria)
Neurologic Central Nervous System Acute episodes of neuropathic symptoms (HCP)
Paresis (HCP)
Peripheral Nervous System HP:0009830 (Peripheral neuropathy)
Behavioral Psychiatric Manifestations HP:0000739 (Anxiety) (HCP)
HP:0000716 (Depression) (HCP)
Insomnia (HCP)
Disorientation (HCP)
HP:0000738 (Hallucinations) (HCP)
paranoia (HCP)
Hematology - Neonatal hemolytic HP:0001903 (Anemia) (harderoporphyria)
Laboratory Abnormalities - Decreased coproporphyrinogen oxidase activity (HCP, lymphocytes, 50% of normal)
Increased coproporphyrin isomer III:I ratio (HCP, feces)
Increased harderoporphyrin excretion (feces, harderoporphyria)
Markedly decreased coproporphyrinogen oxidase activity (harderoporphyria, lymphocytes)
Increased coproporphyrin isomer III:I ratio (HCP, feces)
Increased harderoporphyrin excretion (feces, harderoporphyria)
CPS1 608307 CARBAMOYL PHOSPHATE SYNTHETASE I DEFICIENCY, HYPERAMMONEMIA DUE TO #237300   3 Inheritance - HP:0000007 (Autosomal recessive)
Growth - HP:0001508 (Failure to thrive)
Abdomen Gastrointestinal HP:0002038 (Protein avoidance)
HP:0002013 (Vomiting)
Neurologic -HP:0000737 (Irritability)
HP:0001254 (Lethargy)
HP:0001251 (ataxia)
Coma
Seizures
HP:0002181 (Cerebral edema)
HP:0012758 (neurodevelopmental delay)
HP:0001249 (Intellectual disability)
HP:0001297 (stroke) (rare)
Metabolic Features - HP:0001951 (episodic hyperammonemia)
HP:0001950 (Respiratory alkalosis)
Laboratory Abnormalities - HP:0001987 (hyperammonemia)
Low plasma citrulline
Low plasma arginine
Low urinary orotic acid
Hepatic carbamoylphosphate synthetase I deficiency
Miscellaneous - Two types - lethal neonatal and less severe, late onset
Prevalence of 1 in 200,000 to 1 in 800,000
Decreased citrulline (P)
Decreased arginine (P)
Decreased orotic acid (U)
CPT1A 600528 CARNITINE PALMITOYLTRANSFERASE I DEFICIENCY #255120   3 Inheritance - HP:0000007 (Autosomal recessive)
Cardiovascular Heart HP:0001640 (Cardiomegaly)
Cardiac rhythm disturbances
Abdomen Liver HP:0002240 (Hepatomegaly)
Gastrointestinal HP:0011968 (feeding difficulties)
HP:0002014 (Diarrhea)
Muscle, Soft Tissue - HP:0003324 (Muscle weakness) is not a feature
Neurologic Central Nervous System HP:0008947 (Hypotonia, early)
HP:0001254 (Lethargy)
Seizures
Coma
HP:0004319 (nonprogressive encephalopathy), recurrent
Metabolic Features - Hypoketotic HP:0001943 (Hypoglycemia)
HP:0001947 (Renal tubular acidosis)
Prenatal Manifestations Maternal Acute fatty liver in pregnancy (fetus with carnitine palmitoyltransferase I (CPT1) deficiency)
HELLP syndrome
Laboratory Abnormalities - Mild to moderate HP:0001987 (hyperammonemia)
Transient hyperlipidemia
HP:0003236 (Elevated creatine kinase)
HP:0002910 (abnormal liver enzymes)
No HP:0003215 (dicarboxylic aciduria)
No HP:0002919 (Ketonuria)
Normal to elevated total plasma carnitine
Elevated free carnitine
Carnitine palmitoyltransferase I deficiency (fibroblast, liver, leukocytes)
Decreased CPT1 activity
Decreased long-chain fatty acid oxidation
Miscellaneous - Onset <30 months
Precipitated by infection, fasting, or intercurrent illness
No dicarboxylic aciduria
No ketonuria
Normal to elevated total plasma carnitine
Increased free carnitine
CPT2 600650 CARNITINE PALMITOYLTRANSFERASE II DEFICIENCY, LETHAL NEONATAL #608836   3 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly)
Face High, HP:0000340 (Sloping forehead)
HP:0011220 (Prominent forehead)
Ears HP:0000396 (Overfolded helices)
HP:0000369 (Low-set ears)
HP:0000358 (Posteriorly-rotated ears)
Eyes HP:0000518 (Cataracts)
Nose HP:0000414 (Bulbous nose)
Mouth HP:0000218 (High-arched palate)
HP:0000189 (Narrow palate)
Cardiovascular Heart HP:0001640 (Cardiomegaly)
HP:0001644 (dilated cardiomyopathy)
Thickened myocardium
HP:0011675 (Arrhythmias)
Lipid accumulation in heart
Respiratory - HP:0002098 (Respiratory distress)
HP:0002104 (Apnea)
HP:0002878 (Respiratory failure)
Chest External Features HP:0006610 (Widely spaced nipples)
Abdomen Liver HP:0002240 (Hepatomegaly)
Macrovesicular HP:0001397 (Liver steatosis)
Lipid accumulation in hepatocytes
Liver calcifications
Gastrointestinal HP:0011968 (feeding difficulties)
Genitourinary Kidneys Enlarged HP:0000113 (Polycystic kidneys) (detectable prenatally)
Dysplastic renal parenchyma
HP:0000126 (Hydronephrosis)
Lipid accumulation in kidney, especially in proximal convoluted tubules
HP:0000083 (renal insufficiency)
Ureters HP:0000073 (duplicated ureters)
Skeletal Limbs HP:0004576 (large joint contractures) of knees
HP:0004576 (large joint contractures) of elbows
Hands Long, HP:0001182 (tapered fingers)
Extra digital creases in digits 2-4
Feet Long, tapering toes
Skin, Nails, Hair Nails HP:0001800 (Hypoplastic toenails)
Muscle, Soft Tissue - Lipid accumulation in skeletal muscle
Neurologic Central Nervous System Neonatal HP:0008947 (Hypotonia, early)
HP:0001254 (Lethargy)
Seizures
HP:0002119 (ventriculomegaly)
Intracerebral HP:0007229 (Periventricular calcifications)
Antenatal HP:0001342 (Intracerebral hemorrhage)
Dysplastic or HP:0001274 (agenesis of corpus callosum)
HP:0002126 (Polymicrogyria)
HP:0002269 (Neuronal migration disorder)
Paraventricular cysts
Basal ganglia cysts
Metabolic Features - Nonketotic HP:0001943 (Hypoglycemia)
Prenatal Manifestations Amniotic Fluid HP:0001562 (Oligohydramnios) in some cases
Laboratory Abnormalities - Increased liver function tests
Increased plasma long-chain acylcarnitines
Increased tissue long-chain acylcarnitines
Decreased plasma total and free carnitine
Decreased tissue total and free carnitine
Increased serum long-chain fatty acids
Increased tissue long-chain fatty acids
Long-chain HP:0003215 (dicarboxylic aciduria)
HP:0001987 (hyperammonemia)
Increased total bilirubin
Increased tissue levels of triglycerides
Increased tissue levels of free fatty acids
Severely decreased palmitate oxidation
Severely decreased carnitine palmitoyltransferase II (CPT II) activity (less than 10% of normal) in multiple tissues
Absence of CPT II protein
Miscellaneous - HP:0001699 (Sudden death) within first days of life
See also infantile (600649) and late-onset (255110) CPT II deficiency
Increased long-chain acylcarnitines (P)
Decreased total and free carnitine (P)
Increased long-chain fatty acids (P)
Long-chain dicarboxylic aciduria
CRB2 609720 VENTRICULOMEGALY WITH CYSTIC KIDNEY DISEASE; VMCKD 219730   2 Inheritance - HP:0000007 (Autosomal recessive)
Cardiovascular Heart HP:0001629 (Ventricular septal defect)
Genitourinary Kidneys HP:0000083 (Renal failure)
Echodense kidneys on ultrasound
Echogenic kidneys
Cystic tubular dilatation in the corticomedullary area and medulla
Cysts contain eosinophilic proteinaceous material
Effacement of epithelial foot processes
Skeletal Hands HP:0001162 (Postaxial hand polydactyly) (1 fetus)
Neurologic Central Nervous System HP:0000238 (Hydrocephalus)
HP:0002119 (ventriculomegaly)
Focal hyperplasia of the choroid plexus
Seizures
Gray matter HP:0002282 (heterotopia) (in some patients)
Prenatal Manifestations Amniotic Fluid
HP:0001561 (Polyhydramnios)
Delivery HP:0001622 (Premature delivery) (in some patients)
Laboratory Abnormalities - Increased alpha-fetoprotein in amniotic fluid
Increased acetylcholinesterase (AChE) in amniotic fluid
Miscellaneous - HP:0003577 (prenatal onset)
Most pregnancies with affected fetuses resulted in elective termination
 
CREBBP 600140 RUBINSTEIN-TAYBI SYNDROME 1; RSTS1 180849   2 Inheritance - HP:0000006 (Autosomal dominant)
Growth Height HP:0004322 (short stature)
Average adult male height 153 cm
Average adult female height 147 cm
Weight HP:0001513 (Obesity) after puberty
Other HP:0008897 (Postnatal growth retardation)
Head and Neck Head HP:0000252 (microcephaly)
HP:0000260 (Wide anterior fontanel)
HP:0000270 (Delayed closure of fontanel)
HP:0002007 (Frontal bossing)
Face HP:0000294 (Low anterior hairline)
HP:0000327 (Hypoplastic maxilla)
HP:0000347 (Micrognathia)
HP:0000278 (Retrognathia)
HP:0000273 (Grimacing) or unusual smile with almost closing of the eyes
Ears HP:0000369 (Low-set ears)
Hearing loss
Recurrent HP:0000388 (Otitis media)
Eyes HP:0011229 (Broad eyebrows)
Highly HP:0002553 (Arched eyebrows)
HP:0000527 (Long eyelashes)
HP:0000508 (Ptosis)
HP:0000286 (Epicanthus)
HP:0000486 (Strabismus)
Nasolacrimal duct obstruction
HP:0000518 (Cataracts)
HP:0000501 (Glaucoma)
HP:0000589 (coloboma)
HP:0000494 (Downslanting palpebral fissures)
Nose HP:0000444 (Beaked nose)
Deviated nasal septum
HP:0007965 (Broad nasal bridge)
Mouth HP:0000160 (Small mouth)
HP:0000189 (Narrow palate)
HP:0000218 (High-arched palate)
Teeth HP:0000678 (Dental crowding)
Talon cusps
Crossbite
Screwdriver permanent incisors
HP:0006297 (Enamel hypoplasia)
Enamel discoloration
Cardiovascular Heart HP:0001631 (Atrial septal defect)s
HP:0001629 (Ventricular septal defect)s
Vascular HP:0001643 (Patent ductus arteriosus)
Capillary HP:0001028 (Hemangioma)s
Respiratory - HP:0002205 (Recurrent respiratory infections)
Chest Ribs, Sternum, Clavicles and Scapulae Sternal anomalies
Abdomen Gastrointestinal HP:0002019 (Constipation)
Genitourinary External Genitalia (Male) HP:0000047 (Hypospadias)
HP:0000049 (Shawl scrotum)
Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
Skeletal - HP:0002750 (Delayed bone age)
HP:0001388 (Joint laxity)
Skull Large foramen magnum
HP:0002697 (Parietal foramina)
Spine HP:0002650 (Scoliosis)
HP:0002414 (Spina bifida) occulta
Pelvis Small, flared iliac wings
Limbs HP:0002999 (Patellar dislocations)
Hands HP:0011304 (Broad thumbs) with radial angulation
HP:0004209 (Fifth finger clinodactyly)
Persistent HP:0001212 (fetal fingertip pads)
HP:0006101 (Finger syndactyly)
Polydactyly
HP:0000954 (Single transverse palmar crease)s
Feet HP:0010055 (Broad great toes)
Plantar crease between first and second toes
HP:0001763 (pes planus)
Skin, Nails, Hair Skin HP:0000954 (Single transverse palmar crease)s
Keloid formation in surgical scars
Capillary HP:0001028 (Hemangioma)s
HP:0000957 (Cafe-au-lait spots)
Hair HP:0001007 (Hirsutism)
Neurologic Central Nervous System HP:0001249 (Intellectual disability) (average IQ 51)
HP:0001274 (Agenesis of corpus callosum)
Severe expressive HP:0000750 (Speech delay)
HP:0002311 (Incoordination)
EEG abnormalities
Seizures
HP:0008947 (Hypotonia, early)
HP:0001347 (Hyperreflexia)
Behavioral Psychiatric Manifestations Good social contacts
HP:0000736 (Short attention span)
Labile mood
Immunology - HP:0002783 (Recurrent infections)
Polysaccharide antibody response defect
Neoplasia - Increased risk of tumor formation, especially of the head
Increased risk of leukemia
Laboratory Abnormalities - Ten percent of cases are secondary to submicroscopic deletions of 16p13.3 detectable by FISH
A small minority of patients have translocations and inversions involving 16p13.3
Miscellaneous - Incidence of 1 in 100,000 to 125,000 at birth
Majority of cases are due to de novo mutation
HP:0003828 (Variable severity)
Truncating mutations in CREBBP found in 10% of patients
 
CRH 122560 Nocturnal frontal lobe epilepsy   23593457 2 0  
CRLF1 604237 COLD-INDUCED SWEATING SYNDROME 1; CISS1 272430   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001510 (Growth delay) in infancy
Head and Neck Face Severe contractions of the facial muscles
Facial trismus
Large face
HP:0000293 (Full cheeks)
HP:0000347 (Micrognathia)
HP:0000278 (Retrognathia)
Facial HP:0003324 (Muscle weakness)
Ears HP:0000369 (Low-set ears)
Eyes Chronic HP:0000491 (keratitis)
Inability to fully close eyes during sleep
Nose HP:0005280 (depressed nasal bridge)
HP:0000445 (Broad nose)
HP:0000463 (Anteverted nostrils)
HP:0000343 (Long philtrum)
Mouth HP:0000218 (High-arched palate)
HP:0002307 (drooling)
HP:0000160 (Small mouth)
HP:0000670 (Dental caries), severe
Neck Neck muscle HP:0001276 (Muscle hypertonia)
HP:0000470 (Short neck)
Respiratory - HP:0002094 (dyspnea)
HP:0002104 (Apnea)
Abdomen Gastrointestinal HP:0011968 (feeding difficulties)
Skeletal Spine HP:0002650 (Scoliosis)
HP:0002808 (Kyphosis)
Limbs Elbow HP:0004576 (large joint contractures)
Hands HP:0100490 (Camptodactyly)
HP:0001182 (Tapered fingers)
Ulnar deviation of the fingers
HP:0001181 (Adducted thumbs)
Feet HP:0001762 ( Pes equinovarus)
Skin, Nails, Hair Skin Profuse sweating of the upper body induced by cold exposure
Poor sweating in response to heat
Muscle, Soft Tissue - Generalized muscle contractions, episodic
Tetanus-like muscle contractions
Neurologic Central Nervous System Seizures (less common)
HP:0002179 (Opisthotonus)
HP:0001249 (Intellectual disability) (rare)
Subcortical HP:0002500 (White matter abnormalities) seen on MRI
Peripheral Nervous System Decreased pain sensitivity
Voice - HP:0001611 (Nasal speech)
Metabolic Features - Variable HP:0001945 (Fever)
HP:0001954 (Episodic fever)
Miscellaneous - Onset in early infancy
High early mortality rate if untreated
Muscle contractions in infancy occur in response to tactile stimulation or crying
HP:0001945 (Fever), muscle cramping, and HP:0011968 (feeding difficulties)remit by age 2 years
Cold-induced sweating develops late in the first decade
Clonidine can alleviate HP:0000975 (Hyperhidrosis)
 
CSNK1G1 606274 Severe early-onset epilepsy   24463883 2 0  
CSTB 601145 MYOCLONIC EPILEPSY OF UNVERRICHT AND LUNDBORG #254800   2 Inheritance - HP:0000007 (Autosomal recessive)
Neurologic Central Nervous System Visual blackouts (stage 1)
EEG - polyspike on photic stimulation (stage 1)
Stimulation sensitive segmental HP:0001336 (myoclonus) (stage 2)
Stimulation sensitive generalized HP:0001336 (myoclonus) (stage 3)
Generalized HP:0002069 (Tonic-clonic seizures)(stage 2 and 3)
HP:0002121 (Absence seizures) (stage 2 and 3)
Minor motor impairment (stage 2)
Intermittent wheelchair dependence (stage 3)
EEG - alpha slowing, 4-6 Hz spike waves, HP:0001336 (myoclonus) on photic stimulation (stage 2)
EEG - alpha abolished, continuous spike waves, intense HP:0001336 (myoclonus) on photic stimulation (stage 3)
Action HP:0001336 (myoclonus) (triggered by voluntary movements)
HP:0001251 (ataxia)
Mild HP:0001268 (cognitive decline)
HP:0001260 (Dysarthria)
Miscellaneous - Onset 6-13 years
Three stages of disease progression - Stage 1 (subclinical), Stage 2 (early myoclonic), Stage 3 (disabling myoclonic)
Incidence of 1 in 20,000 live births
High frequency in Finnish population
 
CTC1 613129 CEREBRORETINAL MICROANGIOPATHY WITH CALCIFICATIONS AND CYSTS; CRMCC 612199   5 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Other HP:0001511 (Intrauterine growth retardation) (IUGR)
HP:0008897 (Postnatal growth retardation)
Head and Neck Eyes Coats disease
HP:0007898 (Exudative retinopathy)
Retinal HP:0001009 (Telangiectasia)
Retinal angioma
HP:0000648 (optic atrophy)
HP:0000618 (Blindness)
Mouth HP:0002745 (Oral leukoplakia) (in some patients)
Cardiovascular Vascular Small vessel microangiopathy
Abdomen Gastrointestinal Intestinal bleeding
Telangiectatic mucosal blood vessels
Skeletal - HP:0000938 (Osteopenia)
HP:0000939 (Osteoporosis)
Lytic lesions
HP:0002756 (Pathologic fractures)
Low trabecular bone volume see on bone biopsy
Reduced osteoclasts and osteoblasts
Spine HP:0002650 (Scoliosis)
Limbs Metaphyseal sclerosis
HP:0006487 (Bowing of the long bones)
HP:0002857 (Genua valga)
Short femoral neck
Skin, Nails, Hair Skin HP:0000963 (Thin skin)
Pigmentary abnormalities (in some patients)
Nails HP:0002164 (dysplastic nails)
Hair HP:0008070 (Sparse hair)
Graying hair
Neurologic Central Nervous System HP:0002514 (Intracranial calcifications)
HP:0002415 (Leukodystrophy)
HP:0002352 (leukoencephalopathy)
Seizures
HP:0001257 (Spasticity)
HP:0007325 (generalized dystonia)
HP:0001251 (ataxia)
HP:0001260 (Dysarthria)
HP:0002301 (Hemiplegia)
HP:0001268 (cognitive decline)
HP:0002322 (Resting tremor)
HP:0002071 (extrapyramidal signs)
HP:0007256 (Pyramidal tract signs)
Intracerebral cysts
Hematology - HP:0001903 (Anemia) (less common)
HP:0001873 (thrombocytopenia) (less common)
Bone marrow failure (in some patients)
Laboratory Abnormalities - Shortened telomeres
Miscellaneous - HP:0003593 (Onset in infancy) or early childhood
HP:0003676 (Progressive disorder)
HP:0003812 (Variable phenotype)
 
CTLA4 123890 AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME, TYPE V; ALPS5 616100   2 Inheritance - HP:0000006 (Autosomal dominant)
Respiratory - HP:0002788 (Recurrent upper respiratory infections) (in some patients)
Lung Granulomatous lymphocytic interstitial lung disease
Abdomen Liver HP:0002240 (Hepatomegaly)
Spleen HP:0001744 (Splenomegaly)
Gastrointestinal Lymphocytic enteropathy
HP:0002014 (Diarrhea)
Skeletal - Autoimmune arthritis
Skin, Nails, Hair Skin HP:0000964 (Eczema) (in some patients)
Psoriasis (in some patients)
Neurologic Central Nervous System Lymphocytic infiltration of the brain
Endocrine Features - Autoimmune thyroiditis
Hematology - Autoimmune hemolytic HP:0001903 (Anemia)
Autoimmune HP:0001873 (thrombocytopenia)
Immunology - Peripheral lymphopenia
HP:0002716 (Lymphadenopathy)
Abnormal lymphocytic accumulation in non-lymphoid tissue
Decreased levels of naive T cells
T regulatory cells show poor function
Hyperproliferation of effector T cells
Increased T cell activation
HP:0004313 (Hypogammaglobulinemia)
Decreased memory B cells
Decreased B cell survival and tolerance
HP:0002783 (Recurrent infections) (in some patients)
Autoantibodies
Miscellaneous - Variable age at onset (childhood to adulthood)
HP:0003829 (Incomplete penetrance)
 
CTSA 613111 GALACTOSIALIDOSIS; GSL #256540    2 Skel HP:0000943 (dysostosis multiplex)
Growth HP:0003510 (short stature)
Neuro HP:0001249 (Intellectual disability)
Seizures
Lab EM of skin biopsy and peripheral blood lymphocytes shows membrane-bound fibrillogranular inclusions
Elevated urine sialyloligosaccharides but no free sialic acid
Neuraminidase deficiency
Beta-galactosidase deficiency
Decreased carboxypeptidase-L/protective protein activity
Skin Widespread HP:0001028 (Hemangioma)s
Cardiac Mitral valvular disease
Aortic valvular disease
HEENT HP:0000280 (Coarse facies)
HP:0000524 (Conjunctival telangiectases)
HP:0007957 (corneal opacity)
Macular HP:0010729 (cherry red spot)
Hearing loss
Inheritance HP:0000007 (Autosomal recessive)
GI Usually no organomegaly
Occasionally hepatoHP:0001744 (Splenomegaly)
Vacuolated Kupffer cells
Membrane-bound fibrillogranular inclusions
Increased sialyloligosaccharides but no free sialic acid (U)
CTSD 116840 CEROID LIPOFUSCINOSIS, NEURONAL, 10; CLN10 #610127   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0000340 (Sloping forehead)
Ears HP:0000369 (Low-set ears)
Eyes HP:0000572 (Visual loss), progressive
HP:0000510 (Retinitis pigmentosa)
HP:0001105 (Retinal atrophy)
Nose HP:0007965 (Broad nasal bridge)
Respiratory - HP:0002104 (Apnea)
HP:0002878 (Respiratory failure)
Skeletal Skull Overriding sutures
Obliterated fontanelles
Neurologic Central Nervous System HP:0001257 (Spasticity)
HP:0002063 (Rigidity)
Seizures
HP:0002133 (Status epilepticus)
HP:0001251 (ataxia)
Some patients may show normal early development
HP:0001249 (Intellectual disability), severe
Loss of motor functions
MRI shows HP:0002283 (global brain atrophy)
MRI shows HP:0001272 (Cerebellar atrophy)
HP:0002529 (Neuronal loss) in the cerebrum and cerebellum
Glial activation
White matter lacks axons and myelin
Autofluorescent lipopigment in neurons
Granular osmiophilic cytoplasmic deposits in Schwann cells
Myelin-like lamellar structures in Schwann cells
Laboratory Abnormalities - Decrease or absence of cathepsin D (CTSD) protein immunostaining
Miscellaneous - HP:0003577 (Onset at birth) or early childhood
Patients with null mutations in (CTSD) show a more severe phenotype with HP:0003577 (Onset at birth) ('congenital NCL') and early death within days
Granular osmiophilic cytoplasmic deposits in Schwann cells
Myelin-like lamellar structures in Schwann cells
CTSF 603539 CEROID LIPOFUSCINOSIS, NEURONAL, 13; CLN13 #615362   2 Inheritance - HP:0000007 (Autosomal recessive)
Neurologic Central Nervous System HP:0001268 (cognitive decline), progressive
HP:0000726 (Dementia)
Motor abnormalities
HP:0002322 (Resting tremor)
HP:0001251 (ataxia)
HP:0001260 (Dysarthria)
HP:0001317 (Cerebellar signs)
HP:0002071 (extrapyramidal signs)
Seizures
HP:0002283 (global brain atrophy), diffuse
HP:0001272 (Cerebellar atrophy)
Accumulation of autofluorescent material in neurons
Behavioral Psychiatric Manifestations HP:0000712 (Emotional lability)
HP:0000716 (Depression)
Miscellaneous - Adult onset
HP:0003676 (Progressive disorder)
0
CUL4B 300304 MENTAL RETARDATION, X-LINKED, SYNDROMIC, CABEZAS TYPE; MRXSC #300354   2 Inheritance - HP:0001419 (X-linked recessive)
Growth Height HP:0004322 (short stature) (5th percentile)
Weight Central HP:0001513 (Obesity)
Low birthweight (<10th percentile)
Head and Neck Head HP:0000256 (Macrocephaly), relative
Face HP:0000280 (Coarse facies)
Ears Hypoplastic ear lobes
Eyes Small, HP:0000494 (Downslanting palpebral fissures)
Nose Large HP:0000414 (Bulbous nose)
Mouth HP:0000154 (wide mouth)
HP:0000179 (Thick lower lip vermilion)
HP:0000158 (Macroglossia)
Chest Breasts HP:0000771 (Gynecomastia)
Genitourinary External Genitalia (Male) HP:0000047 (Hypospadias)
HP:0000054 (Small penis)
Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
HP:0008734 (Testicular hypoplasia)
Skeletal - HP:0001388 (Joint laxity)
Spine HP:0002808 (Kyphosis)
Hands HP:0009803 (short fingers)
Feet HP:0009803 (short fingers)
HP:0001773 (Small feet)
HP:0001761 (Pes cavus)
HP:0001763 (pes planus)
HP:0001852 (Sandal gap)
Skin, Nails, Hair Skin Striae
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Wasted lower leg muscles
Neurologic Central Nervous System HP:0001249 (Intellectual disability)
HP:0000750 (Speech delay), severe
HP:0001344 (absent speech) development
HP:0002322 (Resting tremor)
Decreased fine motor coordination
Seizures (onset <2 years)
HP:0001288 (Gait disturbance)
HP:0001251 (ataxia)
Behavioral Psychiatric Manifestations Aggressive outbursts
HP:0000752 (Hyperactivity)
Mood swings
Decreased attention span
Voice - Impaired/HP:0001344 (absent speech)
Endocrine Features - HP:0000823 (Delayed puberty) (in some patients)
HP:0000815 (Hypogonadism) (in some patients)
Miscellaneous - HP:0001999 (Dysmorphic facial features) are variable
 
CYC1 123980 MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 6; MC3DN6 #615453   3 Inheritance - HP:0000007 (Autosomal recessive)
Abdomen Liver Acute HP:0001399 (Liver failure), episodic
Neurologic Central Nervous System HP:0004319 (nonprogressive encephalopathy) during episodes
Coma during episodes (in some patients)
Metabolic Features - HP:0001993 (ketoacidosis), episodic
HP:0003128 (Lactic acidosis), episodic
Endocrine Features - HP:0003074 (Hyperglycemia), insulin-responsive, episodic
Laboratory Abnormalities - HP:0002151 (Increased serum lactate)
HP:0001987 (hyperammonemia), episodic
HP:0002910 (HP:0002910 (abnormal liver enzymes) tests) , episodic
Decreased mitochondrial complex III activity (in liver, muscle, and fibroblasts)
HP:0003593 (Onset in infancy) or early childhood
Episodic decompensation is usually triggered by illness
Lactic acidosis
CYP27A1 606530 CEREBROTENDINOUS XANTHOMATOSIS; CTX #213700   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes Juvenile HP:0000518 (Cataracts)
Cardiovascular Heart HP:0001681 (Angina)
HP:0001658 (Myocardial infarction)
Respiratory Lung HP:0002093 (Respiratory insufficiency)
Skeletal - HP:0000939 (Osteoporosis)
Limbs Tendon xanthomas (Achilles tendon, tibial tuberosity)
MRI of Achilles tendon shows diffuse enlargement of the tendon, multiple hypersignal areas in T(1)- and T(2)-weighted images
Fracture
Skin, Nails, Hair Skin Tuberous HP:0000991 (xanthoma)
Xanthelasma
Neurologic Central Nervous System HP:0000726 (Dementia)
Spinal cord paresis
cerebellar HP:0001251 (ataxia)
HP:0001249 (Intellectual disability)
HP:0001257 (Spasticity)
HP:0007024 (Pseudobulbar paralysis)
Psychiatric symptoms (HP:0000746 (Delusions), HP:0000738 (Hallucinations)
MRI - diffuse or focal cerebral and cerebellar white matter disease
Peripheral Nervous System HP:0009830 (Peripheral neuropathy)
Laboratory Abnormalities - Normal to slightly elevated plasma cholesterol
Elevated plasma cholestanol
Elevated urinary 7 alpha-hydroxylated bile alcohols
Sterol 27-hydroxylase deficiency
Increased cholestanol (P)
Increased 7 alpha-hydroxylated bile alcohols (U)
CYP27B1 609506 VITAMIN D HYDROXYLATION-DEFICIENT RICKETS, TYPE 1A; VDDR1A 264700   3 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
HP:0001510 (Growth delay)
HP:0008897 (Postnatal growth retardation)
Head and Neck Head HP:0002007 (Frontal bossing)
Teeth Delayed tooth eruption
HP:0006297 (Enamel hypoplasia)
Chest Ribs, Sternum, Clavicles and Scapulae Enlargement of the costochondral junction
'Bulging' of the costochondral junction
Deformed rib cage
Abdomen External Features HP:0001538 (Protuberant abdomen) due to HP:0003324 (Muscle weakness)
Skeletal - HP:0002748 (Rickets)
HP:0002757 (Recurrent fractures)
HP:0002653 (Bone pain)
Sparse bone trabeculae
HP:0002753 (Thin bony cortex)
Skull HP:0010537 (Wide cranial sutures)
Posterior flattening of the skull
Limbs Delayed opacification of the epiphyses
Widened, distorted epiphyses
'Bulging' epiphyses
Frayed, HP:0003025 (irregular metaphyses)
Curvatures of the femur, tibia, fibula
Lower limb deformities
HP:0002979 (Bowing of legs)
Enlargement of the wrists
Enlargement of the ankles
Subperiosteal erosions due to secondary HP:0000843 (hyperparathyroidism)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
HP:0003324 (Muscle weakness)
HP:0002355 (Difficulty walking)
Difficulty standing
Neurologic Central Nervous System HP:0001270 (Delayed motor development)
Seizures due to HP:0002901 (hypocalcemia)
Behavioral Psychiatric ManifestationsHP:0000737 (Irritability)
Endocrine Features - Secondary HP:0000843 (hyperparathyroidism)
Laboratory Abnormalities - HP:0002901 (hypocalcemia)
HP:0002148 (Hypophosphatemia)
Increased serum parathyroid hormone (PTH)
HP:0003155 (Increased serum alkaline phosphatase)
Generalized HP:0003355 (Aminoaciduria)
Markedly decreased or absent serum 1,25-dihydroxyvitamin D3
Normal serum 25-hydroxyvitamin D3
Miscellaneous - Clinical onset within first 2 years of life
Can be treated with physiologic levels of 1,25-dihydroxyvitamin D3 or 1-alpha-hydroxyvitamin D3
Increased frequency among French-Canadians from the Charlevoix-Saguenay-Lac Saint Jean area of Quebec (carrier rate 1 in 26)
 
D2HGDH 609186 D-2-HYDROXYGLUTARIC ACIDURIA 1; D2HGA1 #600721   1 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000256 (Macrocephaly)
Face HP:0011220 (Prominent forehead)
HP:0000347 (Micrognathia)
Cardiovascular Heart HP:0001638 (Cardiomyopathy) (severe form)
HP:0001659 (Aortic valve insufficiency)
Respiratory - Inspiratory HP:0010307 (stridor) (severe form)
HP:0002104 (Apnea) (severe form)
Abdomen Gastrointestinal Episodic HP:0002013 (Vomiting) (severe form)
Muscle, Soft Tissue - HP:0003324 (Muscle weakness)
Neurologic Central Nervous System Neonatal/early-infantile onset HP:0004319 (nonprogressive encephalopathy)
HP:0012758 (neurodevelopmental delay), severe
HP:0001249 (Intellectual disability)
HP:0008947 (Hypotonia, early)
Seizures
HP:0002416 (Subependymal cysts)
Delayed gyration
HP:0012448 (Delayed myelination)
Enlarged lateral ventricles (occipital>frontal)
Multifocal cerebral HP:0002500 (White matter abnormalities)
Laboratory Abnormalities - D-2-hydroxyglutaric aciduria
Elevated D-2-hydroxyglutaric acid (urine, plasma, CSF)
Elevated L-2-hydroxyglutaric acid (urine)
Elevated 2-ketoglutarate (urine)
Miscellaneous - Two different phenotypes exist - severe phenotype (early infantile onset, epileptic HP:0004319 (nonprogressive encephalopathy) and often HP:0001638 (Cardiomyopathy) ) and mild phenotype (more variable clinical presentation)
Severe phenotype onset - neonate
Mild phenotype onset - 11-18 months
D-2-hydroxyglutaric aciduria
Increased D-2-hydroxyglutaric acid (U, P, C)
Increased L-2-hydroxyglutaric acid (U)
Increased 2-ketoglutarate (U)
DAG1 128239 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 9; MDDGA9 #616538   5 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000256 (Macrocephaly)
Eyes HP:0000568 (Microphthalmia)
HP:0000557 (Buphthalmos)
HP:0000556 (Retinal dystrophy)
HP:0000518 (Cataracts)
HP:0000545 (Myopia)
HP:0000501 (Glaucoma)
Respiratory - HP:0002878 (Respiratory failure)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
HP:0003560 (Muscular dystrophy)
Absence of immunostaining for alpha-dystroglycan
Absence of immunostaining for alpha- and beta-dystroglycan
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development), severe
HP:0001344 (absent speech)
HP:0002421 (Poor head control)
HP:0000238 (Hydrocephalus)
Thin cortical layer
HP:0002126 (Polymicrogyria)
Frontal HP:0001339 (Agyria)
HP:0002269 (Neuronal migration disorder)
HP:0002119 (Ventriculomegaly)
HP:0002079 (Thin corpus callosum)
Kinking of the pons and brainstem
HP:0006817 (Aplasia/Hypoplasia of the cerebellar vermis)
HP:0002350 (Cerebellar cysts)
HP:0002500 (White matter abnormalities)
HP:0002415 (Leukodystrophy)
Cystic lesions
HP:0002514 (Intracranial calcifications)
Laboratory Abnormalities - HP:0003236 (Increased serum creatine kinase)
Miscellaneous - HP:0003593 (Onset in infancy)
HP:0003828 (Variable severity)
Death in first days of life
Increased serum creatine kinase
DBH 609312 DOPAMINE BETA-HYDROXYLASE DEFICIENCY, CONGENITAL 223360   3 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes HP:0000508 (Ptosis)
Delayed eye opening as a neonate (up to 2 weeks)
Nose Nasal stuffiness
Mouth HP:0000218 (High-arched palate)
Cardiovascular Vascular HP:0001278 (Orthostatic hypotension), severe, recurrent
Fainting spells
Genitourinary Internal Genitalia (Male) Impaired ejaculation due to impaired sympathetic activity
Retrograde ejaculation
Bladder Nocturia
Neurologic Central Nervous System Seizures may occur during hypotensive episodes
Metabolic Features - HP:0001943 (Hypoglycemia), episodic, in infants
HP:0002045 (Hypothermia), episodic, in infants
Laboratory Abnormalities - Undetectable norepinephrine (noradrenaline) in plasma, urine, CSF
Undetectable epinephrine (adrenaline) in plasma, urine, CSF
Greatly increased dopamine in plasma, urine, CSF (approximately 10-fold increase)
Increased plasma dihydroxyphenylacetic acid (DOPAC)
Stimulation of sympathetic fibers results in release of dopamine, not norepinephrine
Undetectable dopamine beta-hydroxylase (DBH) protein in plasma, CSF, or sympathetic fibers
Undetectable plasma DBH activity
Decreased serum prolactin
Undetectable norepinephrine (noradrenaline) (U, P, C) Undetectable epinephrine (adrenaline) (U, P, C)
Increased dopamine (U, P, C)
Increased dihydroxyphenylacetic acid (P)
Decreased serum prolactin
DBT 248610 MAPLE SYRUP URINE DISEASE; MSUD #248600   2 Inheritance - HP:0000007 (Autosomal recessive)
Abdomen Pancreas HP:0001733 (Pancreatitis)
Gastrointestinal HP:0011968 (feeding difficulties)
HP:0002013 (Vomiting)
Neurologic Central Nervous System HP:0001254 (Lethargy)
Seizures
HP:0001251 (ataxia)
Coma
HP:0001249 (Intellectual disability) if untreated
HP:0001276 (Muscle hypertonia)
HP:0008947 (Hypotonia, early)
HP:0002181 (Cerebral edema)
HP:0000738 (Hallucinations)
Brain MRI shows diffusion abnormalities
White matter signal abnormalities in various brain regions
Metabolic Features - Life-threatening metabolic decompensation
HP:0001946 (Ketosis)
HP:0001943 (Hypoglycemia)
HP:0003128 (Lactic acidosis) in E3-deficiency
Laboratory Abnormalities - Elevated plasma branched chain amino acids (leucine, isoleucine, valine)
Maple syrup urine odor
Branched chain ketoaciduria (alpha-keto isocaproate, alpha-keto-beta methylisovalerate, alpha-keto isovalerate)
Elevated plasma alloisoleucine
Positive urine DNPH screening test
Miscellaneous - Five clinical variants of MSUD unassociated with genotype
(1) Classic severe (onset of symptoms 4 to 7 days of age)
(2) Intermittent
(3) Intermediate
(4) Thiamine-responsive form
(5) Dihydrolipoyl dehydrogenase (E3)-deficient
Worldwide incidence of 1 in 185,000 live births
In inbred Old Order Mennonite population of Lancaster County, MSUD prevalence is 1/176 newborns
Death in untreated children
Increased branched chain amino acids (leucine, isoleucine, valine) (P)
Branched chain ketoaciduria (alpha-keto isocaproate, alpha-keto-beta methylisovalerate, alpha-keto isovalerate)
Increased alloisoleucine (P)
Positive urine DNPH screening test
DCHS1 603057 VAN MALDERGEM SYNDROME 1; VMLDS1 601390   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001510 (Growth delay)
Head and Neck Head HP:0000260 (Wide anterior fontanel)s
Face HP:0040199 (Flat midface)
HP:0000341 (Bitemporal narrowing)
HP:0000347 (Micrognathia)
HP:0000327 (Hypoplasia of maxilla)
Ears HP:0008551 (Microtia)
HP:0000413 (Atresia of the external auditory canals)
HP:0000405 (Conductive hearing loss)
HP:0000407 (Sensorineural hearing loss)
Eyes HP:0000316 (Hypertelorism)
HP:0012745 (Short palpebral fissures)
HP:0000508 (Ptosis)
HP:0000286 (Epicanthus)
Nose HP:0007965 (Broad nasal bridge)
Thickening of the nasal alae
Mouth HP:0010804 (Tented upper lip)
HP:0002714 (Downturned mouth)
HP:0000218 (High-arched palate)
Thick gums
Teeth Dental HP:0000689 (Dental malocclusion)
Irregular dentition
Respiratory - HP:0002880 (Respiratory difficulties) due to HP:0002779 (Tracheomalacia)
Airways HP:0002779 (Tracheomalacia) (tracheostomy may be required)
Chest External Features HP:0000774 (Narrow chest)
Ribs, Sternum, Clavicles and Scapulae HP:0000894 (Short clavicles)
Abdomen Gastrointestinal HP:0011968 (feeding difficulties)
HP:0001545 (Anteriorly placed anus)
HP:0002023 (Anal atresia)
Genitourinary External Genitalia (Male) HP:0000047 (Hypospadias)
Kidneys HP:0000089 (Renal hypoplasia)
Skeletal - HP:0001388 (Joint laxity)
HP:0002652 (Skeletal dysplasia)
HP:0000938 (Osteopenia)
Skull HP:0010537 (Wide cranial sutures)
Thickened skull base
Thickened frontal bones
Spine HP:0002650 (Scoliosis)
Limbs Subluxation of the radial heads
Hands Hand deformities
HP:0010044 (Short fourth metacarpals)
HP:0004209 (Fifth finger clinodactyly)
Flexion of the PIP joints
Webbing of the fingers
HP:0006101 (Finger syndactyly), cutaneous
Feet HP:0001760 (Foot deformities)
HP:0001762 ( Pes equinovarus)
HP:0004689 (Short fourth metatarsals)
Skin, Nails, Hair Skin HP:0000960 (Sacral dimple)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System HP:0001249 (Intellectual disability)
Periventricular nodular HP:0002282 (heterotopia)
Subcortical band HP:0002282 (heterotopia)
HP:0001302 (pachygyria)
HP:0009879 (Simplified gyral pattern)
HP:0002079 (Thin corpus callosum)
Miscellaneous - HP:0003577 (Onset at birth)
Some features may be variable
 
DCX 300121 LISSENCEPHALY, X-LINKED, 1; LISX1 #300067   2 Inheritance - X-linked
Head and Neck Eyes HP:0000639 (Nystagmus)
Neurologic Central Nervous System HP:0001249 (Intellectual disability)
Seizures
HP:0001270 (Delayed motor development)
Axial HP:0008947 (Hypotonia, early)
HP:0001251 (ataxia)
HP:0001260 (Dysarthria)
Limb HP:0001257 (Spasticity)
HP:0001302 (pachygyria)
HP:0001339 (Agyria)
HP:0001339 (Lissencephaly) (anterior to posterior decreasing gradient of severity, more prominent in anterior brain regions)
Subcortical band or laminar HP:0002282 (heterotopia) (in female carriers)
Malformation of the insula
HP:0001274 (agenesis of corpus callosum)
Miscellaneous - HP:0003593 (Onset in infancy)
HP:0003812 (Variable phenotype) in females
HP:0003829 (Incomplete penetrance)
Somatic or germline mosaicism may occur
 
DDX3X 300160 MENTAL RETARDATION, X-LINKED 102; MRX102 300958   2 Inheritance - HP:0001423 (X-linked dominant)
HP:0001419 (X-linked recessive)
Growth Weight HP:0004325 (Low weight) (in some patients)
Head and Neck Head HP:0000252 (microcephaly) (in some patients)
Face HP:0001999 (Dysmorphic facial features) (in some patients)
EarsHP:0000410 (Hearing loss, mixed) (in some patients)
Eyes HP:0000505 (Visual impairment) (in some patients)
Mouth HP:0100333 (Unilateral cleft lip) (in some patients)
HP:0000175 (Cleft palate) (in some patients)
Skeletal - HP:0001388 (Joint laxity) (in some patients)
Spine HP:0002650 (Scoliosis) (in some patients)
Skin, Nails, Hair Skin Pigmentation abnormalities (in some patients)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System HP:0001249 (Intellectual disability), variable
Seizures (in some patients)
HP:0100022 (Movement disorder)s (in some patients)
HP:0100660 (dyskinesia) (in some patients)
HP:0002136 (Wide-based gait) (in some patients)
HP:0001257 (Spasticity) (in some patients)
HP:0002079 (Hypoplasia of corpus callosum) (in some patients)
HP:0002119 (ventriculomegaly) (in some patients)
HP:0002539 (Cortical dysplasia) (in some patients)
Behavioral Psychiatric Manifestations HP:0000729 (Autistic behavior) (in some patients)
HP:0000752 (Hyperactivity) (in some patients)
HP:0000718 (Aggressive behavior) (in some patients)
Endocrine Features - HP:0000826 (Precocious puberty) (in some patients)
Miscellaneous - HP:0003593 (Onset in infancy)
No consistent dysmorphic facial phenotype
Affected girls have de novo heterozygous mutations consistent with HP:0001423 (X-linked dominant) inheritance
 
DEPDC5 614191 EPILEPSY, FAMILIAL FOCAL, WITH VARIABLE FOCI; FFEVF #604364   2 Inheritance - HP:0000006 (Autosomal dominant)
Neurologic Central Nervous System Seizure, focal or multifocal onset
Temporal lobe epilepsy
Parietal lobe epilepsy
Frontal lobe epilepsy
Secondary generalization
Nocturnal seizures (in some patients)
HP:0011157 (Auras)
Automatisms
HP:0001249 (Intellectual disability) (in some patients)
Abnormal interictal EEG (in some patients)
Focal HP:0002539 (Cortical dysplasia) (in some patients)
Cortical thickening at the bottom of the sulcus (in some patients)
Behavioral Psychiatric Manifestations HP:0000729 (autistic behaviour) (in some patients)
Miscellaneous - Variable age at onset (range infancy to adulthood)
Onset usually in first or second decades
Phenotypic variability
HP:0003829 (Incomplete penetrance)
 
DGKZ 601441 Epilepsy   26795593 2 0  
DGUOK 601465 MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE); MTDPS3 #251880   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001510 (Growth delay)
HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000252 (microcephaly) (less common)
Eyes HP:0000639 (Nystagmus)
Disconjugate eye movements
HP:0001093 (Optic nerve dysplasia)
Abdomen External Features HP:0001541 (Ascites)
Portal HP:0000822 (Hypertension)
Liver HP:0002240 (Hepatomegaly)
HP:0002910 (HP:0002910 (abnormal liver enzymes) tests)
Liver tissue shows 80 to 99% depletion of mitochondrial DNA (mtDNA) with decreased activities of mitochondrial-encoded respiratory chain complexes
Biopsy shows micronodular HP:0001394 (liver cirrhosis)
HP:0001396 (Cholestasis)
HP:0001397 (Liver steatosis)
HP:0000952 (Jaundice)
Hepatocellular loss
Hepatocellular necrosis
PeriHP:0006580 (Portal fibrosis)
Pseudoacinar formation
Electron microscopy shows increased and HP:0012103 (Abnormality of the mitochondrion)
HP:0001399 (Liver failure)
Spleen HP:0001744 (Splenomegaly)
Gastrointestinal HP:0011968 (feeding difficulties)
HP:0002013 (Vomiting)
Skin, Nails, Hair Skin HP:0000952 (Jaundice)
Neurologic Central Nervous System HP:0004319 (nonprogressive encephalopathy)
HP:0000639 (Nystagmus)
HP:0008947 (Hypotonia, early)
HP:0001347 (Hyperreflexia)
Seizures
HP:0002283 (global brain atrophy)
Peripheral Nervous System HP:0009830 (Peripheral neuropathy)
Metabolic Features - HP:0001943 (Hypoglycemia)
HP:0002045 (Hypothermia)
HP:0003128 (Lactic acidosis)
Hematology - HP:0003256 (Coagulopathy) due to HP:0001399 (Liver failure)
HP:0001873 (thrombocytopenia)
Laboratory Abnormalities - HP:0002904 (Hyperbilirubinemia)
HP:0002910 (HP:0002910 (abnormal liver enzymes) tests)
HP:0003073 (Hypoalbuminemia)
Generalized HP:0003355 (Aminoaciduria)
Miscellaneous - Onset as neonate
HP:0001399 (Liver failure) develops in first months of life
Most patients die of HP:0001399 (Liver failure) by 9 months of age
Lactic acidosis
Abnormal liver function tests
DHCR24 606418 DESMOSTEROLOSIS 602398   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000252 (microcephaly)
HP:0000256 (Macrocephaly), relative
Face HP:0002007 (Frontal bossing)
HP:0000347 (Micrognathia)
Ears HP:0000358 (Posteriorly rotated ears)
HP:0000369 (Low-set ears)
Eyes HP:0000486 (Strabismus)
HP:0000639 (Nystagmus)
Nose HP:0005281 (Hypoplastic nasal bridge)
HP:0003196 (Short nose)
HP:0000463 (Anteverted nares)
Mouth HP:0009085 (Thick alveolar ridges)
Gingival nodules
HP:0000175 (Cleft palate)
Cardiovascular Heart HP:0005160 (Total anomalous pulmonary venous drainage)
Genitourinary External Genitalia (Male) HP:0000062 (Ambiguous genitalia)
External Genitalia (Female) HP:0000062 (Ambiguous genitalia)
Skeletal - HP:0002804 (Arthrogryposis)
HP:0005789 (Osteosclerosis)
Limbs HP:0008905 (rhizomelia)
Hands HP:0004576 (large joint contractures) of the hands
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development), severe
HP:0001257 (Spasticity)
Seizures
HP:0002119 (ventriculomegaly)
HP:0000238 (Hydrocephalus)
Decreased white matter
Partial or complete HP:0001274 (agenesis of corpus callosum)
Effaced gyral pattern
Laboratory Abnormalities - Elevated plasma desmosterol
HP:0003812 (Variable phenotype)
HP:0001999 (Dysmorphic facial features) may not be present
Increased desmosterol (P)
DHCR7 602858 SMITH-LEMLI-OPITZ SYNDROME; SLOS #270400   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Weight Birth weight <2500gm
Other HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0000347 (Micrognathia)
HP:0000341 (Bitemporal narrowing)
Ears HP:0000369 (Low-set ears)
HP:0000358 (Posteriorly rotated ears)
Eyes HP:0000508 (Ptosis)
HP:0000286 (Epicanthus)
HP:0000518 (Cataracts)
HP:0000316 (Hypertelorism)
HP:0000486 (Strabismus)
Nose HP:0000463 (Anteverted nares)
HP:0000431 (Broad nasal bridge)
Mouth HP:0000175 (Cleft palate)
HP:0000171 (Hypoplastic tongue)
HP:0000187 (Broad alveolar ridges)
Teeth Large central front teeth
HP:0000678 (Dental crowding)
Cardiovascular Heart HP:0001629 (Ventricular septal defect)
HP:0001631 (Atrial septal defect)
Vascular HP:0001680 (Coarctation of aorta)
HP:0001643 (Patent ductus arteriosus)
Respiratory Lung HP:0002089 (Pulmonary hypoplasia)
Incomplete lobulation of the lungs
Abdomen Gastrointestinal HP:0002033 (Poor suck)
HP:0002013 (Vomiting)
HP:0002019 (Constipation)
HP:0002566 (Malrotation)
HP:0002021 (Pyloric stenosis)
Genitourinary External Genitalia (Male) HP:0000047 (Hypospadias)
HP:0000062 (Ambiguous genitalia)
HP:0000054 (Small penis)
HP:0000046 (Hypoplastic scrotum)
HP:0000048 (Bifid scrotum)
Microurethra
Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
Kidneys HP:0000104 (Renal agenesis)
HP:0000126 (Hydronephrosis)
Single kidney
Cystic kidneys
Ureters Ureteropelvic junction obstruction
Skeletal - HP:0010655 (Stippled epiphyses)
Pelvis HP:0002827 (Hip dislocations)
Hip subluxation
Limbs Limb shortening
Hands HP:0009778 (Short thumbs)
HP:0001162 (Postaxial hand polydactyly)
HP:0009623 (Proximally placed thumbs)
Feet HP:0006101 (Finger syndactyly) of second and third toes
HP:0001162 (Postaxial hand polydactyly)
TaliHP:0001848 (Pes calcaneovalgus)
Short, broad toes
HP:0001845 (Overriding toes)
HP:0001840 (Metatarsus adductus)
Skin, Nails, Hair Skin Severe HP:0000992 (Photosensitivity)
HP:0000964 (Eczema)
Facial capillary HP:0001028 (Hemangioma)
Hair Blonde hair
Neurologic Central Nervous System HP:0001249 (Intellectual disability)
Seizures
HP:0008947 (Hypotonia, early) (early infancy)
HP:0001276 (Muscle hypertonia) (childhood)
HP:0000238 (Hydrocephalus)
HP:0007333 (Hypoplasia of the frontal lobes)
Periventricular gray matter HP:0002282 (heterotopia)s
Abnormal sleep pattern
Behavioral Psychiatric Manifestations Self injurious behavior
HP:0000718 (Aggressive behavior)
Voice - Shrill screaming
Prenatal Manifestations Movement HP:0001558 (Decreased fetal movement)
Delivery Breech presentation
Laboratory Abnormalities - Low cholesterol
Elevated 7-dehydrocholesterol
Miscellaneous - Estimated incidence 1/20,000 - 1/40,000
Decreased cholesterol (P)
Increased 7-dehydrocholesterol (P)
DHFR 126060 MEGALOBLASTIC ANEMIA DUE TO DIHYDROFOLATE REDUCTASE DEFICIENCY #613839   1 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0011968 (feeding difficulties)
Head and Neck Head HP:0000252 (microcephaly), acquired
Eyes Icterus
Eyelid HP:0001336 (myoclonus)
Abdomen Liver HP:0002240 (Hepatomegaly)
Skin, Nails, Hair Skin Pallor
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
HP:0002121 (Absence seizures)
Seizures, refractory
HP:0002421 (Poor head control)
HP:0001251 (ataxia)
HP:0001328 (Learning disabilities)
HP:0002283 (global brain atrophy)
HP:0001321 (Cerebellar hypoplasia) and atrophy
HP:0012448 (Delayed myelination)
Neuronal and vascular calcifications
Hematology - Megaloblastic HP:0001903 (Anemia)
HP:0001876 (Pancytopenia)
Hypersegmented neutrophils
HP:0001873 (thrombocytopenia)
Laboratory Abnormalities - Normal serum folate
Decreased CSF tetrahydrofolate and 5-methyltetrahydrofolate
Decreased activity of dihydrofolate reductase
Miscellaneous - HP:0003828 (Variable severity)
Severe form with onset at 3 to 4 months of age and severe HP:0012758 (neurodevelopmental delay)
Milder form with onset in childhood, HP:0002121 (Absence seizures), and HP:0001328 (Specific learning disability)
Treatment with folinic acid offers some benefit for HP:0001903 (Anemia) and seizure control
Megaloblastic anemia
Decreased tetrahydrofolate and 5-methyltetrahydrofolate )
DIAPH1 602121 SEIZURES, CORTICAL BLINDNESS, AND MICROCEPHALY SYNDROME; SCBMS #616632   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Other HP:0001510 (Growth delay)
Head and Neck Head HP:0000252 (microcephaly) (up to -10 SD)
Eyes Cortical HP:0000618 (Blindness)
HP:0000648 (optic atrophy)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early) (in some patients)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development), moderate to severe
Seizures
HP:0000750 (language delay)
HP:0002079 (Hypoplasia of the corpus callosum)
Miscellaneous - Onset of seizures in first months of life
 
DLD 238331 DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY; DLDD #246900   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly)
Cardiovascular Heart HP:0001639 (hypertrophic cardiomyopathy)
Abdomen Liver HP:0002240 (Hepatomegaly) (in some patients)
HP:0001410 (Liver dysfunction) (in some patients)
Gastrointestinal HP:0002013 (Vomiting), recurrent, severe
HP:0011968 (feeding difficulties)
Neurologic Central Nervous System HP:0004319 (nonprogressive encephalopathy), episodic
HP:0001263 (Delayed psychomotor development) (in most patients)
HP:0008947 (Hypotonia, early)
HP:0001254 (Lethargy)
HP:0001251 (ataxia)
HP:0007325 (generalized dystonia)
Seizures
Leigh syndrome (in some patients)
Metabolic Features - HP:0001942 (metabolic acidosis)
HP:0003128 (Lactic acidosis)
Episodic decompensation
Laboratory Abnormalities - HP:0001943 (Hypoglycemia)
Elevated pyruvate (in most patients)
Elevated branched-chain amino acids (in most patients)
Elevated alpha-ketoglutarate (in most patients)
Decreased activities of the pyruvate dehydrogenase complex, the alpha-ketoglutarate dehydrogenase complex, and the branched-chain alpha-keto acid dehydrogenase complex
HP:0002910 (HP:0002910 (abnormal liver enzymes) tests) (in some patients)
Miscellaneous - Onset usually in the neonatal period although later onset has been reported
Some patients may have normal psychomotor development
Highly HP:0003828 (Variable severity)
High mortality in infancy and early childhood (in some patients)
Metabolic acidosis
Lactic acidosis
Increased pyruvate
Increased branched-chain amino acids
Increased alpha-ketoglutarate
DLG3 300189 MENTAL RETARDATION, X-LINKED 90; MRX90 300850   2 Inheritance - HP:0001419 (X-linked recessive)
Head and Neck Eyes HP:0000486 (Strabismus)
HP:0000582 (Upslanting palpebral fissures) (1 family)
Mouth HP:0000218 (High-arched palate) (1 family)
Teeth Molar hypoplasia (1 family)
Chest External Features HP:0000774 (Narrow chest) (1 family)
Genitourinary Bladder HP:0000805 (Enuresis)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
HP:0001249 (Intellectual disability), mild to severe
HP:0000750 (language delay)
Seizures
Behavioral Psychiatric Manifestations HP:0000708 (behavioral disturbance)
Attention-deficit HP:0000752 (Hyperactivity) disorder
Miscellaneous - Affected females have been reported
 
DNAJC5 611203 CEROID LIPOFUSCINOSIS, NEURONAL, 4B, AUTOSOMAL DOMINANT; CLN4B #162350    2 Inheritance - HP:0000006 (Autosomal dominant)
Neurologic Central Nervous System Seizures
HP:0000726 (Dementia)
Speech deterioration
HP:0001336 (myoclonus)
HP:0001317 (Cerebellar signs)
cerebellar HP:0001251 (ataxia)
HP:0001300 (Parkinsonism) may occur
HP:0002071 (extrapyramidal signs)
Autofluorescent lipopigment in neurons
Behavioral Psychiatric Manifestations Behavioral changes
HP:0000716 (Depression)
Auditory and visual HP:0000738 (Hallucinations)
Laboratory Abnormalities - 'Fingerprint' profiles ultrastructurally
'Curvilinear' profiles ultrastructurally
'Rectilinear' profiles ultrastructurally
Granular osmiophilic deposits (GROD) in cells
Miscellaneous - Onset in adulthood (third to fourth decade)
Rapidly progressive
For similar HP:0000007 (Autosomal recessive) form, see CLN4 (204300)
Fingerprint' profiles ultrastructurally
'Curvilinear' profiles ultrastructurally
'Rectilinear' profiles ultrastructurally
DNAJC6 608375 PARKINSON DISEASE 19, JUVENILE-ONSET; PARK19 615528   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Face HP:0000298 (Mask-like facies)
Eyes HP:0000571 (Hypometric saccades)
Neurologic Central Nervous System HP:0001300 (Parkinsonism)
HP:0002067 (Bradykinesia)
HP:0002063 (Rigidity)
HP:0002362 (Shuffling gait)
HP:0002172 (Postural instability)
HP:0002322 (Resting tremor)
HP:0000298 (Mask-like facies)
HP:0001260 (Dysarthria)
HP:0001249 (Intellectual disability) (1 family)
Seizures (1 family)
HP:0007325 (generalized dystonia) (1 family)
HP:0007256 (Pyramidal tract signs) (1 family)
Onset of HP:0001300 (Parkinsonism) in first decade
Rapidly progressive
Patients become wheelchair-bound about 10 years after onset
 
DNM1 602377 EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 31; EIEE31 #616346   1 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Eyes Poor or absent visual fixation
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System Epileptic HP:0004319 (nonprogressive encephalopathy)
HP:0001263 (global developmental delay) (in some patients)
HP:0002376 (Psychomotor regression)
Seizures, refractory
HP:0001249 (Intellectual disability), severe to profound
HP:0001344 (absent speech)
HP:0002540 (inability to walk)
HP:0002355 (Difficulty walking)
HP:0002521 (hypsarrhythmia) seen on EEG
Multifocal discharges
Spike-wave discharges
Background slowing
HP:0002283 (global brain atrophy) (in some patients)
Behavioral Psychiatric Manifestations HP:0100716 (Self-injurious behavior) (in some patients)
Miscellaneous - Onset in first months of life
Some patients may show normal early development before seizure onset
De novo mutations
 
DNMT3A 602769 TATTON-BROWN-RAHMAN SYNDROME; TBRS 615879   2 Inheritance - HP:0000006 (Autosomal dominant)
Growth Height HP:0000098 (Tall stature) (+3 S.D)
Head and Neck Head HP:0000256 (macrocephaly) (+2.5 SD)
Face HP:0000311 (Round face)
Eyes Heavy horizontal eyebrows
HP:0012745 (Short palpebral fissures)
Cardiovascular Heart HP:0001631 (Atrial septal defect) (less common)
Abdomen External Features HP:0001537 (Umbilical hernia) (less common)
Skeletal Spine HP:0002650 (Scoliosis) (less common)
Neurologic Central Nervous System HP:0001249 (Intellectual disability), mild to moderate
Seizures (less common)
 
DOCK6 614194 ADAMS-OLIVER SYNDROME 2; AOS2 614219   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly)
HP:0000256 (Macrocephaly) (rare)
HP:0001057 (Aplasia cutis congenita) of the scalp
Face Mild HP:0001999 (Dysmorphic features)
Low hair line
Bitemporal HP:0000716 (Depression) (rare)
Ears HP:0000369 (Low-set ears)
HP:0000411 (Prominent ears) (rare)
Eyes HP:0000316 (Hypertelorism)
HP:0012745 (Short palpebral fissures)
HP:0000486 (Strabismus) (rare)
HP:0000568 (Microphthalmia) (rare)
HP:0000518 (Cataracts), congenital (rare)
Rod dystrophy (rare)
Vitreoretinal abnormalities, congenital (rare)
HP:0000648 (optic atrophy) (rare)
Nose HP:0005280 (depressed nasal bridge)
HP:0000414 (Bulbous nasal tip)
Mouth HP:0000347 (Micrognathia)
Skeletal Limbs Terminal transverse defects, asymmetric (minimal to absence of a limb)
Hands Shortened digits
HP:0000954 (Single transverse palmar crease)
Feet Shortened digits
Webbing, interdigital
Skin, Nails, Hair Skin HP:0001057 (Aplasia cutis congenita) of the scalp
HP:0000965 (Cutis marmorata)
Prominent veins on scalp, trunk, and/or extremities
Nails HP:0001792 (Hypoplastic nails)
Hair HP:0000294 (Low anterior hairline)
Muscle, Soft Tissue - HP:0001004 (Lymphedema), of upper and/or lower extremity (rare)
Neurologic Central Nervous System HP:0001263 (global developmental delay)
Seizures
HP:0008947 (Hypotonia, early)
Calcifications of cerebral ventricles
HP:0002119 (ventriculomegaly)
HP:0002126 (Polymicrogyria) (rare)
HP:0002283 (global brain atrophy) (rare)
HP:0001321 (Cerebellar hypoplasia), mild asymmetric (rare)
Retrocerebellar cyst (rare)
Prenatal Manifestations Amniotic Fluid HP:0001562 (Oligohydramnios)
Miscellaneous - Limb reduction defects typically involve the distal phalanges or entire digit, with rare involvement of more proximal limb structures
 
DOCK7 615730 EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 23; EIEE23 #615859   1 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Face HP:0000629 (Periorbital fullness)
HP:0000341 (Bitemporal narrowing)
HP:0000322 (Short philtrum)
Ears HP:0000377 (Abnormally shaped ears)
Eyes Cortical HP:0000505 (Visual impairment)
Cortical HP:0000618 (Blindness)
HP:0000506 (telecanthus)
HP:0000574 (Thick eyebrows)
Nose Large nasal root
HP:0000455 (Broad nasal tip)
HP:0000463 (Anteverted nares)
Mouth HP:0012471 (full lips)
Skin, Nails, Hair Hair HP:0000294 (Low anterior hairline)
Neurologic Central Nervous System Epileptic HP:0004319 (nonprogressive encephalopathy)
HP:0001263 (Delayed psychomotor development)
Regression of early motor skills
Seizures, intractable
HP:0002521 (hypsarrhythmia)
Abnormally marked pontobulbar sulcus
HP:0012110 (hypoplasia of the pons), mild
Abnormal T2-weighted signals in the occipital white and gray matter
Occipital lobe atrophy
HP:0002079 (Thin corpus callosum)
Miscellaneous - HP:0003593 (Onset in infancy)
 
DOLK 610746 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Im; CDG1M 610768   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height Normal birth length
Weight Normal birth weight
Other HP:0001508 (Failure to thrive)
Head and Neck Head Normal birth head circumference
HP:0000252 (microcephaly), acquired
Eyes HP:0000535 (Sparse eyebrows)
HP:0000653 (Sparse eyelashes)
Cardiovascular Heart HP:0001644 (dilated cardiomyopathy)
Skin, Nails, Hair Skin HP:0008064 (ichthyosis)
Hair HP:0000535 (Sparse eyebrows)
HP:0000653 (Sparse eyelashes)
Minimal hair growth
Neurologic Central Nervous System HP:0008947 (Hypotonia, early), profound muscular (in some patients)
Seizures (in some patients)
HP:0002521 (hypsarrhythmia) (in some patients)
Metabolic Features - Hypoketotic HP:0001943 (Hypoglycemia) (in some patients)
Laboratory Abnormalities - Abnormal transferrin isoelectric focusing (IEF)
Increased disialo- and asialotransferrin
Decreased lipid-linked oligosaccharides (LLO)
Miscellaneous - Death in early infancy (in some patients)
Some patients present with apparent nonsyndromic HP:0001644 (dilated cardiomyopathy) in early childhood
Isoelectric focusing of serum transferrin (type I) Decreased lipid-linked oligosaccharides (LLO)
DPAGT1 191350 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ij; CDG1J #608093   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0001999 (Dysmorphic features)
Eyes HP:0000518 (Cataracts)
HP:0000639 (Nystagmus)
HP:0000486 (Strabismus)
Respiratory - HP:0002093 (Respiratory insufficiency)
Asphyxia
HP:0002104 (Apnea)
Chest Breasts HP:0003186 (Inverted nipples)
Genitourinary Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
Skeletal - Joint HP:0004576 (large joint contractures)
Hands HP:0004209 (Fifth finger clinodactyly)
HP:0000954 (Single transverse palmar crease)
Fetal fat pads
Skin, Nails, Hair Skin Skin dimples on upper thighs
HP:0000952 (Jaundice)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
HP:0001249 (Intellectual disability)
HP:0008947 (Hypotonia, early)
HP:0001276 (Muscle hypertonia) of extremities
HP:0002322 (Resting tremor)
HP:0001347 (Hyperreflexia)
Seizures
Behavioral Psychiatric Manifestations HP:0000718 (Aggressive behavior) (in 1 family)
Hematology - Chronic HP:0001903 (Anemia) (in 1 patient)
Prolonged APPT (in 1 patient)
Antithrombin III deficiency (in 1 patient)
Laboratory Abnormalities - HP:0002910 (HP:0002910 (abnormal liver enzymes) tests) (in 1 patient)
Hypoproteinemia (in 1 patient)
Abnormal isoelectric focusing of serum transferrin (type 1 pattern)
Miscellaneous - HP:0003577 (Onset at birth)
HP:0003828 (Variable severity)
Isoelectric focusing of serum transferrin (type I)
DPM1 603503 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ie; CDG1E #608799   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000252 (microcephaly), acquired
HP:0005469 (Flat occiput)
Face HP:0000319 (smooth philtrum)
HP:0000347 (Micrognathia)
Eyes HP:0000316 (Hypertelorism)
HP:0000486 (Strabismus)
HP:0000639 (Nystagmus)
HP:0000494 (Downslanting palpebral fissures)
Cortical HP:0000618 (Blindness)
HP:0000648 (optic atrophy)
Retinopathy
Nose HP:0000431 (Broad nasal bridge)
Mouth High, HP:0000189 (Narrow palate)
HP:0002705 (High, narrow palate)
Inverted 'V-shaped' mouth
Cardiovascular Vascular HP:0001643 (Patent ductus arteriosus)
Respiratory - HP:0002098 (Respiratory distress)
Abdomen Liver HP:0002240 (Hepatomegaly)
Spleen HP:0001744 (Splenomegaly)
Skeletal Limbs Shortening of the arms
Knee HP:0004576 (large joint contractures)
Ankle HP:0004576 (large joint contractures)
Hands HP:0200055 (Small hands)
HP:0100490 (Camptodactyly)
Skin, Nails, Hair Skin HP:0001009 (Telangiectasia)
HP:0001028 (Hemangioma)s
Nails HP:0002164 (dysplastic nails)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
HP:0003560 (Muscular dystrophy)
Wide variation in fiber size
Decreased glycosylation of alpha-dystroglycan
Neurologic Central Nervous System Global HP:0012758 (neurodevelopmental delay), severe
HP:0008947 (Hypotonia, early)
Seizures
cerebellar HP:0001251 (ataxia)
HP:0002322 (Resting tremor)
HP:0001347 (Increased deep tendon reflexes) in the lower limbs
No visual fixation
Abnormal EEG with epileptiform changes
PontoHP:0001272 (Cerebellar atrophy)
Decreased myelination seen on MRI
T2-weighted hyperintensities in subcortical brain regions seen on MRI
Hematology - Antithrombin III deficiency
Protein S deficiency
Protein C deficiency
Prolonged activated partial thromboplastin time (aPTT)
Laboratory Abnormalities - Abnormal isoelectric focusing of serum transferrin (type I pattern)
Decreased tetrasialotransferrin levels
Increased disialotransferrin and asialotransferrin levels
Increased liver function tests
HP:0003236 (Increased serum creatine kinase)
Miscellaneous - HP:0003593 (Onset in infancy)
HP:0003676 (Progressive disorder)
HP:0003828 (Variable severity)
Isoelectric focusing of serum transferrin (type I)
DPM2 603564 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Iu; CDG1U 615042   1 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly), postnatal
Face HP:0002058 (Myopathic facies)
HP:0000347 (Micrognathia)
Eyes HP:0000601 (Hypotelorism)
HP:0000648 (optic atrophy) (in 1 of 3 patients)
HP:0000486 (Strabismus)
Nose HP:0003196 (Small nose)
Mouth HP:0000218 (High-arched palate)
HP:0000219 (Thin upper lip)
Respiratory - HP:0002098 (Respiratory distress) at birth
Abdomen Gastrointestinal HP:0011968 (feeding difficulties)
Skeletal - Congenital HP:0004576 (large joint contractures)
Spine HP:0002650 (Scoliosis)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early), severe
Dystrophic changes seen on muscle biopsy
Reduced O-mannosyl glycans on alpha-dystroglycan
Neurologic Central Nervous System HP:0001263 (Lack of psychomotor development)
Seizures, refractory
Primitive reflexes
Absence of spontaneous movements
HP:0001321 (Cerebellar hypoplasia)
Loss of cerebral white matter (in 1 of 3 patients)
Laboratory Abnormalities - HP:0003236 (Increased serum creatine kinase)
Increased serum transaminases (in 1 of 3 patients)
Abnormal N-glycosylation of transferrin
Fibroblasts accumulate Dol-PP-GlcNAc2Man5
Miscellaneous - HP:0003577 (Onset at birth)
HP:0001522 (Death in early childhood)
Isoelectric focusing of serum transferrin (type I)
DPM3 605951 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Io; CDG1O 612937   3 0 Isoelectric focusing of serum transferrin (type I)
DPYD 612779 DIHYDROPYRIMIDINE DEHYDROGENASE DEFICIENCY #274270   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
HP:0008897 (Postnatal growth retardation)
Head and Neck Head HP:0000252 (microcephaly)
Eyes HP:0000496 (oculomotor abnormalities)
HP:0000568 (Microphthalmia)
HP:0000589 (coloboma)
HP:0000639 (Nystagmus)
HP:0000648 (optic atrophy)
Neurologic Central Nervous System Seizures
HP:0001270 (Delayed motor development)
HP:0001249 (Intellectual disability)
HP:0000750 (language delay)
HP:0001254 (Lethargy)
HP:0008947 (Hypotonia, early)
HP:0001276 (Muscle hypertonia)
HP:0002445 (Tetraplegia)
HP:0002500 (White matter abnormalities)
HP:0002283 (global brain atrophy)
HP:0001274 (agenesis of corpus callosum) (rare)
Behavioral Psychiatric Manifestations HP:0000752 (Hyperactivity)
HP:0000717 (Autism)
Laboratory Abnormalities - Increased urinary uracil
Increased urinary thymine
Decreased or absent dihydropyrimidine dehydrogenase activity
Miscellaneous - HP:0003812 (Variable phenotype)
Onset usually in infancy although later onset may occur
Some individuals are asymptomatic
Heterozygous mutation carriers show toxicity to 5-fluorouracil (5FU)
Increased uracil (U)
Increased thymine (U)
DPYS 613326 DIHYDROPYRIMIDINASE DEFICIENCY; DPYSD 222748   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0008897 (Postnatal growth retardation)
Head and Neck Head HP:0001357 (Plagiocephaly)
Face HP:0001999 (Dysmorphic facial features)
Abdomen Gastrointestinal Low HP:0002023 (Anal atresia)
Skeletal Hands HP:0009803 (Hypoplastic phalanges)
Feet HP:0001762 ( Pes equinovarus)
HP:0009803 (Hypoplastic phalanges)
Neurologic Central Nervous System Seizures (about 50% of patients)
HP:0001249 (Intellectual disability) (3 patients)
HP:0000750 (Speech delay)
Extrapyramidal HP:0100660 (dyskinesia)s
HP:0007256 (Pyramidal tract signs)
HP:0002500 (White matter abnormalities)
Laboratory Abnormalities - Increased uracil and dihydrouracil in bodily fluids
Increased thymine and dihydrothymine in bodily fluids
Miscellaneous - HP:0003812 (Variable phenotype)
About half of individuals are asymptomatic and identified by newborn screening programs
High frequency in Japan (2 in 20,000, 0.1%)
Mutation carriers may show toxicity to 5-fluorouracil (5FU)
Increased uracil and dihydrouracil (U, P, C)
Increased thymine and dihydrothymine (U, P, C)
DYNC1H1 600112 MENTAL RETARDATION, AUTOSOMAL DOMINANT 13; MRD13 #614563   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Head HP:0000252 (microcephaly) (in some patients)
HP:0011220 (Prominent forehead) (in some patients)
Face HP:0001999 (Dysmorphic features), mild (in some patients)
Skeletal Hands HP:0200055 (Small hands) (in some patients)
Feet HP:0001760 (Foot deformities) (in some patients)
Neurologic Central Nervous System HP:0001249 (Intellectual disability) (in some patients)
Seizures, generalized
Focal seizures
Spastic HP:0002445 (Tetraplegia) (in some patients)
HP:0001288 (Gait disturbance)
HP:0001302 (pachygyria), usually posterior
HP:0002126 (Polymicrogyria), usually frontal (in some patients)
Nodular HP:0002282 (heterotopia) (in some patients)
HP:0002079 (Thin corpus callosum) (in some patients)
Dysmorphic basal ganglia (in some patients)
HP:0001321 (Cerebellar hypoplasia) (in some patients)
HP:0002365 (Brainstem hypoplasia) (in some patients)
Peripheral Nervous System HP:0003477 (Peripheral axonal neuropathy) (in some patients)
HP:0001265 (Hyporeflexia) (in some patients)
Behavioral Psychiatric Manifestations HP:0000729 (autistic behaviour) (in some patients)
Miscellaneous - Most patients have de novo mutations
HP:0001999 (Dysmorphic features) are mild or variable
 
DYRK1A 600855 MENTAL RETARDATION, AUTOSOMAL DOMINANT 7; MRD7 #614104   2 0  
EARS2 612799 COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 12; COXPD12 #614924   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Eyes HP:0000508 (Ptosis)
HP:0000544 (Ophthalmoplegia)
HP:0000505 (Visual impairment)
Mouth HP:0000175 (Cleft palate)
Cardiovascular Heart HP:0005144 (Ventricular septal hypertrophy)
Abdomen Liver HP:0002240 (Hepatomegaly)
Macrovesicular HP:0001397 (Liver steatosis)
Fibrosis, mild
HP:0001396 (Cholestasis)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early), neonatal
Muscle biopsy shows cytochrome c oxidase-negative fibers
HP:0003200 (Ragged-red fibers)
Decreased activities of mitochondrial complexes I, III, and IV
Impaired mitochondrial respiration
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development) (in severe cases)
HP:0002376 (Psychomotor regress)(in milder cases)
Spastic HP:0030182 (Tetraparesis/tetraplegia) (in severe cases)
HP:0007325 (generalized dystonia) (in severe cases)
HP:0002067 (Bradykinesia) (in severe cases)
Lack of head or postural control (in severe cases)
HP:0001344 (absent speech) (in severe cases)
Seizures
Swelling of the deep white matter seen on MRI
T2-weighted hyperintensities in deep cerebral white matter, brainstem, and cerebellar white matter with sparing of the periventricular rim
Swelling of the cerebral white matter
HP:0002079 (Hypoplasia of the corpus callosum)
HP:0006989 (Dysplastic corpus callosum)
Increased cerebral lactate
Metabolic Features - HP:0003128 (Lactic acidosis)
Laboratory Abnormalities - HP:0002151 (Increased serum lactate)
HP:0002910 (HP:0002910 (abnormal liver enzymes) tests) , intermittent
Increased alpha-fetoprotein
Miscellaneous - Onset in first year of life
Two main phenotypes, severe and mild
Mild cases show clinical, biochemical, and MRI improvement after the second year of life
Increased lactate (P)
EBP 300205 CHONDRODYSPLASIA PUNCTATA 2, X-LINKED DOMINANT; CDPX2 302960 21634086 2 Inheritance - HP:0001419 (X-linked recessive)
Growth Height HP:0004322 (short stature)
Head and Neck Face MicroHP:0000278 (Retrognathia) HP:0011800 (Midface hypoplasia)
Ears HP:0000369 (Low-set ears)
Eyes HP:0000518 (Cataracts)
Nose HP:0000426 (High nasal bridge) Short nasal root
Mouth HP:0000218 (High-arched palate)
Cardiovascular Heart Cardiac malformations HP:0001650 (Aortic stenosis)
Genitourinary External Genitalia (Male) HP:0000028 (Cryptorchidism)
Skeletal Spine HP:0002650 (Scoliosis) HP:0002808 (Kyphosis)
Hands Digital anomalies Polydactyly HP:0010557 (Overlapping fingers) HP:0100807 (Long fingers)
Feet 2-3 toe HP:0006101 (Finger syndactyly)
HP:0001845 (Overlapping toes)
Skin, Nails, Hair Skin Collodion skin changes HP:0008064 (ichthyosis) Pigmentary abnormalities
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development) (in all patients)
HP:0001249 (Intellectual disability) (in all patients)
HP:0001276 (Muscle hypertonia) of the extremities Seizures HP:0000238 (Hydrocephalus) HP:0001305 (Dandy-Walker malformation) Hypoplasia or HP:0001274 (agenesis of corpus callosum)
Laboratory Abnormalities - Increased plasma 8-dihydrocholesterol and 8(9)-cholestenol
Miscellaneous - HP:0003812 (Variable phenotype)
Phenotype is due to hypomorphic nonmosaic mutation in the EBP gene
Increased 8(9)-cholestenol (P)
Increased 8-dehydrocholesterol (P)
ECHS1 602292 MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 DEFICIENCY; ECHS1D #616277   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Ears Hearing impairment
Eyes HP:0000639 (Nystagmus)
Cardiovascular Heart HP:0001629 (Ventricular septal defect)
Obstructive HP:0001639 (hypertrophic cardiomyopathy)
Respiratory - HP:0002104 (Apnea), episodic
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Secondarily decreased activities of mitochondrial respiratory enzymes
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development), severe
HP:0001257 (Spasticity)
Abnormal T2-weighted hyperintensities in the basal ganglia consistent with Leigh syndrome
Laboratory Abnormalities - HP:0002151 (Increased serum lactate)
HP:0002490 (Increased CSF lactate)
Increased urinary glyoxylate
Secondarily decreased activity of the pyruvate dehydrogenase complex (PDC)
Increased urinary S-(2-carboxypropyl)cysteine (1 family)
Increased 2-methyl-2,3-dihydroxybutyrate (1 family)
Miscellaneous - HP:0003577 (Onset at birth)
Severe disorder
Increased glyoxylate (U)
Increased S-(2-carboxypropyl)cysteine (U)
Increased 2-methyl-2,3-dihydroxybutyrate
ECM1 602201 LIPOID PROTEINOSIS OF URBACH AND WIETHE 247100   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Face Acneform lesions
Eyes HP:0200034 (Papules) along the eyebrows and palpebral fissures
Mouth HP:0200034 (Papules) on the lips
Pharyngeal lesions
Thickened tongue
Respiratory Larynx Laryngeal lesions resulting in hoarseness
Skin, Nails, Hair Skin Yellow, papular lesions of the lip, soft palate, pharynx
HP:0001072 (Thickened skin) over the elbows and along the fingers
Verrucous lesions
Acneform facial lesions
Skin Histology Deposition of hyaline material in the skin
Hair Patchy HP:0001596 (Alopecia)
Neurologic Central Nervous System HP:0002354 (Memory impairment)
Episodic absence-like spells
Seizures
HP:0002514 (Intracranial calcifications) in the anterior mesial temporal lobes
Calcification of the amygdala and the amygdala-hippocampal transition area
Behavioral Psychiatric Manifestations Executive dysfunction
Paranoia
HP:0000718 (Aggressive behavior)
HP:0000738 (Hallucinations)
Absence of fear
Voice - HP:0001609 (Hoarse voice) due to laryngeal infiltration
Miscellaneous - Onset in childhood
Neuropsychiatric manifestations are variable
 
EEF1A2 602959 EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 33; EIEE33 #616409   1 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Head HP:0000252 (microcephaly), acquired
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early), neonatal
Neurologic Central Nervous System Epileptic HP:0004319 (nonprogressive encephalopathy)
HP:0001263 (Delayed psychomotor development), severe
Seizures
Limited or HP:0001344 (absent speech)
HP:0002317 (Unsteady gait)
HP:0002521 (hypsarrhythmia)
Behavioral Psychiatric Manifestations HP:0000729 (autistic behaviour)
HP:0000718 (Aggressive behavior)
Miscellaneous - HP:0003593 (Onset in infancy)
De novo mutation
 
EFTUD2 603892 MANDIBULOFACIAL DYSOSTOSIS, GUION-ALMEIDA TYPE; MFDGA 610536   2 Inheritance - HP:0000006 (Autosomal dominant)
Growth Height HP:0004322 (short stature) (of varying degrees)
Head and Neck Head HP:0000252 (microcephaly), progressive (-3 to 6 SD)
HP:0000243 (Trigonocephaly)
Face HP:0011800 (Midface hypoplasia)
HP:0000272 (Malar hypoplasia)
HP:0002002 (Prominent philtrum)
HP:0000347 (Micrognathia)
Buccal tags
Ears HP:0008551 (Microtia)
Preauricular skin tags
HP:0000413 (External auditory meatus atresia)
HP:0000369 (Low-set ears)
HP:0000396 (Overfolded helices)
Hypoplasia of the upper part of the helix
HP:0000377 (Dysplastic ears)
ConductiveHP:0000410 (Hearing loss, mixed)
Eyes HP:0000582 (Upslanting palpebral fissures)
HP:0000494 (Downslanting palpebral fissures)
HP:0000286 (Epicanthus)
HP:0000506 (telecanthus)
Nose HP:0000453 (choanal atresia) (in some patients)
HP:0000463 (Upturned nose)
HP:0003196 (Short nose)
HP:0000463 (Anteverted nares)
Mouth HP:0000175 (Cleft palate) (in some patients)
Cardiovascular Heart HP:0001631 (Atrial septal defect)
HP:0001629 (Ventricular septal defect) (in some patients)
Respiratory - Breathing difficulties due to HP:0000453 (choanal atresia)
Abdomen Gastrointestinal Esophageal atresia (in some patients)
HP:0011968 (feeding difficulties)
Skeletal Hands HP:0100258 (Preaxial polydactyly)
HP:0001238 (Slender fingers)
HP:0009623 (Proximally placed thumbs) (in some patients)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
Severe HP:0000750 (Speech delay)
Seizures (in some patients)
Miscellaneous - De novo mutation resulting in haploinsufficiency of EFTUD2 (603892)
 
EGF 131530 HYPOMAGNESEMIA 4, RENAL; HOMG4 611718   2 0  
EHMT1 607001 KLEEFSTRA SYNDROME #610253   2 Inheritance - HP:0000006 (Autosomal dominant)
HP:0003745 (Isolated cases)
Growth Weight HP:0001513 (Obesity)
Head and Neck Head HP:0000248 (Brachycephaly)
HP:0000252 (microcephaly)
Face HP:0012368 (Flat face)
HP:0000303 (Prognathism)
HP:0011800 (Midface hypoplasia)
HP:0000280 (Coarse facies)
Ears HP:0000377 (Dysplastic ears)
Hearing loss
Eyes HP:0000316 (Hypertelorism)
HP:0000664 (Synophrys)
HP:0000582 (Upslanting palpebral fissures)
Nose HP:0000463 (Anteverted nares)
Mouth HP:0010806 (Carp-shaped mouth)
HP:0000179 (Thick lower lip vermilion)
HP:0000158 (Macroglossia)
Cardiovascular Heart Conotruncal HP:0002564 (Congenital heart defect)s
Skeletal Hands HP:0009803 (short fingers)
HP:0000954 (Single transverse palmar crease)s
Skin, Nails, Hair Hair HP:0000664 (Synophrys)
Neurologic Central Nervous System HP:0001249 (Intellectual disability), severe
HP:0008947 (Hypotonia, early)
Seizures
Behavioral Psychiatric Manifestations HP:0000708 (behavioral disturbance)
HP:0002360 (Sleep disturbance)
HP:0000722 (Obsessive-compulsive disorder)
HP:0000733 (Stereotypic behavior)
HP:0000718 (Aggressive behavior)
Miscellaneous - Many cases have submicroscopic subtelomeric deletions of chromosome 9q leading to haploinsufficiency of EHMT1 (607001)
 
EIF2B1 606686 LEUKOENCEPHALOPATHY WITH VANISHING WHITE MATTER; VWM 603896   5 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head Cessation of head growth in affected infants
HP:0000256 (Macrocephaly) may develop in those who survive past age 2 years
Eyes HP:0000648 (optic atrophy)
HP:0000618 (Blindness) may occur in affected infants
Genitourinary Internal Genitalia (Female) HP:0008209 (Premature ovarian failure), in a subset of affected patients ovarioleukodystrophy
HP:0008193 (Primary gonadal insufficiency)
Neurologic Central Nervous System Deterioration of motor development
HP:0002317 (Unsteady gait)
Loss of coordination
Chronic-progressive course with episodes of rapid deterioration following HP:0001945 (Fever) or head trauma
Rapid, instantaneous neurologic decline may occur after fright
HP:0002376 (Psychomotor regression) in affected children
HP:0001288 (Gait disturbance)
HP:0008947 (Hypotonia, early)
HP:0001254 (Lethargy)
Seizures
HP:0001257 (Spasticity)
Mild mental decline
HP:0002354 (Memory impairment)
HP:0100543 (Cognitive impairment)
HP:0001260 (Dysarthria)
HP:0002352 (leukoencephalopathy), severe
Cavitating HP:0002352 (leukoencephalopathy)
Cystic degeneration of cerebral white matter with preserved cortex
Over time, white matter vanishes and is replaced by CSF
MRI shows symmetric, diffuse lesions with CSF-like signal intensity
Biopsy shows white matter HP:0003429 (Hypomyelination), HP:0007305 (CNS demyelination), HP:0002171 (Gliosis)
Biopsy shows foamy lipid-laden macrophages
White matter rarefaction and cystic degeneration
Decreased amount of myelin-specific proteins
Decreased amount of myelin-specific lipids
Magnetic resonance spectroscopy (MRS) shows decreased N-acetylaspartic acid in unaffected white matter
MRS shows decreased choline in affected white matter
MRS shows decreased creatine in white matter
Behavioral Psychiatric Manifestations HP:0000751 (Personality change)
HP:0000746 (Delusions)
Indifference
HP:0000712 (Emotional lability)
Psychiatric manifestations more common with adult-onset of disease
Endocrine Features - Subset of patients with ovarioleukodystrophy have primary HP:0000141 (amenorrhea)
Secondary HP:0000141 (amenorrhea)
Increased serum gonadotropins
Decreased serum estrogen
Decreased serum progesterone
Miscellaneous - Onset usually in late infancy or childhood (1 to 6 years)
Onset may also occur in early infancy, adolescence, or adulthood
Early death occurs in affected infants (days to months after disease onset)
 
EIF2B2 606454 LEUKOENCEPHALOPATHY WITH VANISHING WHITE MATTER; VWM 603896   5 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head Cessation of head growth in affected infants
HP:0000256 (Macrocephaly) may develop in those who survive past age 2 years
Eyes HP:0000648 (optic atrophy)
HP:0000618 (Blindness) may occur in affected infants
Genitourinary Internal Genitalia (Female) HP:0008209 (Premature ovarian failure), in a subset of affected patients (ovarioleukodystrophy)
HP:0008193 (Primary gonadal insufficiency)
Neurologic Central Nervous System Deterioration of motor development
HP:0002317 (Unsteady gait)
Loss of coordination
Chronic-progressive course with episodes of rapid deterioration following HP:0001945 (Fever) or head trauma
Rapid, instantaneous neurologic decline may occur after fright
HP:0002376 (Psychomotor regression) in affected children
HP:0001288 (Gait disturbance)
HP:0008947 (Hypotonia, early)
HP:0001254 (Lethargy)
Seizures
HP:0001257 (Spasticity)
Mild mental decline
HP:0002354 (Memory impairment)
HP:0100543 (Cognitive impairment)
HP:0001260 (Dysarthria)
HP:0002352 (leukoencephalopathy), severe
Cavitating HP:0002352 (leukoencephalopathy)
Cystic degeneration of cerebral white matter with preserved cortex
Over time, white matter vanishes and is replaced by CSF
MRI shows symmetric, diffuse lesions with CSF-like signal intensity
Biopsy shows white matter HP:0003429 (Hypomyelination), HP:0007305 (CNS demyelination), HP:0002171 (Gliosis)
Biopsy shows foamy lipid-laden macrophages
White matter rarefaction and cystic degeneration
Decreased amount of myelin-specific proteins
Decreased amount of myelin-specific lipids
Magnetic resonance spectroscopy (MRS) shows decreased N-acetylaspartic acid in unaffected white matter
MRS shows decreased choline in affected white matter
MRS shows decreased creatine in white matter
Behavioral Psychiatric Manifestations HP:0000751 (Personality change)
HP:0000746 (Delusions)
Indifference
HP:0000712 (Emotional lability)
Psychiatric manifestations more common with adult-onset of disease
Endocrine Features - Subset of patients with ovarioleukodystrophy have primary HP:0000141 (amenorrhea)
Secondary HP:0000141 (amenorrhea)
Increased serum gonadotropins
Decreased serum estrogen
Decreased serum progesterone
Miscellaneous - Onset usually in late infancy or childhood (1 to 6 years)
Onset may also occur in early infancy, adolescence, or adulthood
Early death occurs in affected infants (days to months after disease onset)
 
EIF2B3 606273 LEUKOENCEPHALOPATHY WITH VANISHING WHITE MATTER; VWM 603896   5 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head Cessation of head growth in affected infants
HP:0000256 (Macrocephaly) may develop in those who survive past age 2 years
Eyes HP:0000648 (optic atrophy)
HP:0000618 (Blindness) may occur in affected infants
Genitourinary Internal Genitalia (Female) HP:0008209 (Premature ovarian failure), in a subset of affected patients (ovarioleukodystrophy)
HP:0008193 (Primary gonadal insufficiency)
Neurologic Central Nervous System Deterioration of motor development
HP:0002317 (Unsteady gait)
Loss of coordination
Chronic-progressive course with episodes of rapid deterioration following HP:0001945 (Fever) or head trauma
Rapid, instantaneous neurologic decline may occur after fright
HP:0002376 (Psychomotor regression) in affected children
HP:0001288 (Gait disturbance)
HP:0008947 (Hypotonia, early)
HP:0001254 (Lethargy)
Seizures
HP:0001257 (Spasticity)
Mild mental decline
HP:0002354 (Memory impairment)
HP:0100543 (Cognitive impairment)
HP:0001260 (Dysarthria)
HP:0002352 (leukoencephalopathy), severe
Cavitating HP:0002352 (leukoencephalopathy)
Cystic degeneration of cerebral white matter with preserved cortex
Over time, white matter vanishes and is replaced by CSF
MRI shows symmetric, diffuse lesions with CSF-like signal intensity
Biopsy shows white matter HP:0003429 (Hypomyelination), HP:0007305 (CNS demyelination), HP:0002171 (Gliosis)
Biopsy shows foamy lipid-laden macrophages
White matter rarefaction and cystic degeneration
Decreased amount of myelin-specific proteins
Decreased amount of myelin-specific lipids
Magnetic resonance spectroscopy (MRS) shows decreased N-acetylaspartic acid in unaffected white matter
MRS shows decreased choline in affected white matter
MRS shows decreased creatine in white matter
Behavioral Psychiatric Manifestations HP:0000751 (Personality change)
HP:0000746 (Delusions)
Indifference
HP:0000712 (Emotional lability)
Psychiatric manifestations more common with adult-onset of disease
Endocrine Features - Subset of patients with ovarioleukodystrophy have primary HP:0000141 (amenorrhea)
Secondary HP:0000141 (amenorrhea)
Increased serum gonadotropins
Decreased serum estrogen
Decreased serum progesterone
Miscellaneous - Onset usually in late infancy or childhood (1 to 6 years)
Onset may also occur in early infancy, adolescence, or adulthood
Early death occurs in affected infants (days to months after disease onset)
 
EIF2B4 606687 LEUKOENCEPHALOPATHY WITH VANISHING WHITE MATTER; VWM 603896   5 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head Cessation of head growth in affected infants
HP:0000256 (Macrocephaly) may develop in those who survive past age 2 years
Eyes HP:0000648 (optic atrophy)
HP:0000618 (Blindness) may occur in affected infants
Genitourinary Internal Genitalia (Female) HP:0008209 (Premature ovarian failure), in a subset of affected patients (ovarioleukodystrophy)
HP:0008193 (Primary gonadal insufficiency)
Neurologic Central Nervous System Deterioration of motor development
HP:0002317 (Unsteady gait)
Loss of coordination
Chronic-progressive course with episodes of rapid deterioration following HP:0001945 (Fever) or head trauma
Rapid, instantaneous neurologic decline may occur after fright
HP:0002376 (Psychomotor regression) in affected children
HP:0001288 (Gait disturbance)
HP:0008947 (Hypotonia, early)
HP:0001254 (Lethargy)
Seizures
HP:0001257 (Spasticity)
Mild mental decline
HP:0002354 (Memory impairment)
HP:0100543 (Cognitive impairment)
HP:0001260 (Dysarthria)
HP:0002352 (leukoencephalopathy), severe
Cavitating HP:0002352 (leukoencephalopathy)
Cystic degeneration of cerebral white matter with preserved cortex
Over time, white matter vanishes and is replaced by CSF
MRI shows symmetric, diffuse lesions with CSF-like signal intensity
Biopsy shows white matter HP:0003429 (Hypomyelination), HP:0007305 (CNS demyelination), HP:0002171 (Gliosis)
Biopsy shows foamy lipid-laden macrophages
White matter rarefaction and cystic degeneration
Decreased amount of myelin-specific proteins
Decreased amount of myelin-specific lipids
Magnetic resonance spectroscopy (MRS) shows decreased N-acetylaspartic acid in unaffected white matter
MRS shows decreased choline in affected white matter
MRS shows decreased creatine in white matter
Behavioral Psychiatric Manifestations HP:0000751 (Personality change)
HP:0000746 (Delusions)
Indifference
HP:0000712 (Emotional lability)
Psychiatric manifestations more common with adult-onset of disease
Endocrine Features - Subset of patients with ovarioleukodystrophy have primary HP:0000141 (amenorrhea)
Secondary HP:0000141 (amenorrhea)
Increased serum gonadotropins
Decreased serum estrogen
Decreased serum progesterone
Miscellaneous - Onset usually in late infancy or childhood (1 to 6 years)
Onset may also occur in early infancy, adolescence, or adulthood
Early death occurs in affected infants (days to months after disease onset)
 
EIF2B5 603945 LEUKOENCEPHALOPATHY WITH VANISHING WHITE MATTER; VWM 603896   5 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head Cessation of head growth in affected infants
HP:0000256 (Macrocephaly) may develop in those who survive past age 2 years
Eyes HP:0000648 (optic atrophy)
HP:0000618 (Blindness) may occur in affected infants
Genitourinary Internal Genitalia (Female) HP:0008209 (Premature ovarian failure), in a subset of affected patients (ovarioleukodystrophy)
HP:0008193 (Primary gonadal insufficiency)
Neurologic Central Nervous System Deterioration of motor development
HP:0002317 (Unsteady gait)
Loss of coordination
Chronic-progressive course with episodes of rapid deterioration following HP:0001945 (Fever) or head trauma
Rapid, instantaneous neurologic decline may occur after fright
HP:0002376 (Psychomotor regression) in affected children
HP:0001288 (Gait disturbance)
HP:0008947 (Hypotonia, early)
HP:0001254 (Lethargy)
Seizures
HP:0001257 (Spasticity)
Mild mental decline
HP:0002354 (Memory impairment)
HP:0100543 (Cognitive impairment)
HP:0001260 (Dysarthria)
HP:0002352 (leukoencephalopathy), severe
Cavitating HP:0002352 (leukoencephalopathy)
Cystic degeneration of cerebral white matter with preserved cortex
Over time, white matter vanishes and is replaced by CSF
MRI shows symmetric, diffuse lesions with CSF-like signal intensity
Biopsy shows white matter HP:0003429 (Hypomyelination), HP:0007305 (CNS demyelination), HP:0002171 (Gliosis)
Biopsy shows foamy lipid-laden macrophages
White matter rarefaction and cystic degeneration
Decreased amount of myelin-specific proteins
Decreased amount of myelin-specific lipids
Magnetic resonance spectroscopy (MRS) shows decreased N-acetylaspartic acid in unaffected white matter
MRS shows decreased choline in affected white matter
MRS shows decreased creatine in white matter
Behavioral Psychiatric Manifestations HP:0000751 (Personality change)
HP:0000746 (Delusions)
Indifference
HP:0000712 (Emotional lability)
Psychiatric manifestations more common with adult-onset of disease
Endocrine Features - Subset of patients with ovarioleukodystrophy have primary HP:0000141 (amenorrhea)
Secondary HP:0000141 (amenorrhea)
Increased serum gonadotropins
Decreased serum estrogen
Decreased serum progesterone
Miscellaneous - Onset usually in late infancy or childhood (1 to 6 years)
Onset may also occur in early infancy, adolescence, or adulthood
Early death occurs in affected infants (days to months after disease onset)
 
ELOVL4 605512 ICHTHYOSIS, SPASTIC QUADRIPLEGIA, AND MENTAL RETARDATION; ISQMR 614457   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001510 (Growth delay)
Head and Neck Head HP:0000252 (microcephaly)
Eyes HP:0000649 (Abnormal visual evoked potentials)
High HP:0000545 (Myopia)
Respiratory - Asthma
Abdomen External Features HP:0000023 (Inguinal hernia)
Genitourinary External Genitalia (Male) HP:0008734 (Small testes)
Skeletal - HP:0004576 (large joint contractures)
Skin, Nails, Hair Skin HP:0008064 (ichthyosis)
HP:0000958 (Dry skin)
HP:0040189 (Scaly skin)
Erythema
HP:0007543 (epidermal hyperkeratosis)
Collodion membrane at birth
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay), profound
HP:0001263 (Lack of psychomotor development)
HP:0001249 (Intellectual disability), profound
Seizures
HP:0002123 (Myoclonic seizures)
Spastic HP:0002445 (quadriplegia)
Immobility
HP:0001276 (Hypertonicity)
HP:0012448 (Delayed myelination)
HP:0002283 (Generalized brain atrophy)
Miscellaneous - HP:0003577 (Onset at birth)
0
ELP4 606985 Language impairment, developmental delay, autism, and epilepsy   26010655 2 0  
EML1 602033 Neuronal heterotopia, epilepsy, intellectual disability   24859200 2 0  
EMX2 600035 SCHIZENCEPHALY 269160   2 0  
ENG 131195 TELANGIECTASIA, HEREDITARY HEMORRHAGIC, OF RENDU, OSLER, AND WEBER; HHT 187300   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Eyes HP:0000524 (Conjunctival telangiectases)
Nose Spontaneous, recurrent HP:0000421 (epistaxis) (onset childhood)
Nasal mucosa HP:0100579 (Mucosal telangiectases)
Mouth Lip HP:0001009 (Cutaneous telangiectases)
Tongue HP:0100579 (Mucosal telangiectases)
Palate HP:0100579 (Mucosal telangiectases)
Cardiovascular Heart Right-to-left shunt
High-output HP:0001635 (Congestive heart failure)
Vascular Arterial aneurysm
Venous varicosities
Arteriovenous fistulas of celiac and mesenteric vessels
Respiratory - HP:0002094 (dyspnea)
Lung Pulmonary HP:0100026 (Arteriovenous malformation) (PAVM), especially lower lobes
HP:0000961 (Cyanosis)
Abdomen HP:0001394 (liver cirrhosis)
Hepatic HP:0100026 (Arteriovenous malformation)
Gastrointestinal GI hemorrhage (onset usually in 5th -6th decade)
Angiodysplasia
HP:0100579 (Mucosal telangiectases) (stomach, duodenum, small bowel, colon)
HP:0100026 (Arteriovenous malformation)
Melena
Hematochezia
Hematemesis
Skeletal Hands Nail bed HP:0001009 (Cutaneous telangiectases)
Finger pad HP:0001009 (Cutaneous telangiectases)
Clubbing
Skin, Nails, Hair Skin HP:0001009 (Cutaneous telangiectases) (especially on tongue, lips, palate, fingers, face, conjunctiva, trunk, nail beds, and fingertips)
Neurologic Central Nervous System Cerebral HP:0100026 (Arteriovenous malformation)
HP:0002076 (Migraine)
HP:0002326 (Transient ischemic attack)
Ischemic HP:0001297 (stroke)
Seizure
HP:0001276 (Subarachnoid hemorrhage)
Spinal HP:0100026 (Arteriovenous malformation)
HP:0001342 (Intracerebral hemorrhage)
Brain abscess
Paradoxical cerebral emboli
Hematology - HP:0001901 (Polycythemia)
HP:0001903 (Anemia)
Miscellaneous - Definite diagnosis if 3/4 criteria present (HP:0000421 (epistaxis), HP:0001009 (Telangiectasia), visceral lesion, or family history)
Cutaneous telangiectases often not evident until 20-30 years of age Incidence 1 in 5,000-8,000
Genetic heterogeneity
PAVMs occur more frequently in hereditary hemorrhagic HP:0001009 (Telangiectasia) 1 (HHT1) than HHT2
 
EOMES 604615 Malformations of cortical development, epilepsy   19536565 2 0  
EPG5 615068 VICI SYNDROME; VICIS 242840   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Post natal HP:0008897 (Postnatal growth retardation)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0000316 (Hypertelorism)
Ears HP:0000369 (Low-set ears)
HP:0000407 (sensorineural hearing loss) (in some patients)
Eyes Bilateral HP:0000518 (Cataracts)
HP:0001107 (Ocular albinism)
Retinal HP:0007513 (Generalized hypopigmentation)
HP:0000639 (Nystagmus)
Mouth HP:0100333 (Unilateral cleft lip)
HP:0000175 (Cleft palate)
HP:0000347 (Micrognathia)
Cardiovascular Heart HP:0001638 (Cardiomyopathy) , dilated
HP:0001712 (Left ventricular hypertrophy)
Systolic dysfunction
HP:0001635 (Congestive heart failure)
Respiratory Airways HP:0200117 (Recurrent respiratory tract infections)
Genitourinary External Genitalia (Male) HP:0000047 (Hypospadias), penile
Skin, Nails, Hair Skin Skin HP:0007513 (Generalized hypopigmentation)
HP:0001022 (Cutaneous albinism)
Chronic mucocutaneous candidiasis
Hair Hair HP:0007513 (Generalized hypopigmentation)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
HP:0003756 (Myopathy)
Variation in fiber size
Internal nuclei
HP:0012103 (Abnormality of the mitochondrion)
Numerous vacuole-like areas
Redundancy of basal lamina with accumulated debris
Neurologic Central Nervous System HP:0008947 (Hypotonia, early)
Abnormal posturing
HP:0001274 (agenesis of corpus callosum)
HP:0006817 (Aplasia/Hypoplasia of the cerebellar vermis)
Profound HP:0001263 (global developmental delay)
White matter neuronal HP:0002282 (heterotopia)
Bilateral HP:0010636 (schizencephaly)
Seizures
Immunology - HP:0002783; HP:0004798; Recurrent bacterial, viral, and fungal infections
Skin anergy to recall antigens
Profound depletion of T4+ lymphocytes
HP:0000777 (Thymic hypoplasia)
Lack of delayed skin hypersensitivity reaction
Decreased serum immunoglobulins
Defective humoral response
Laboratory Abnormalities - Reduced IgG levels, particularly IgG2 subclass
Normal IgA levels
Normal IgM levels
Miscellaneous - HP:0003577 (Onset at birth)
Early death often occurs from HP:0001635 (Cardiac failure) or infection
Immunologic defects are variable
 
EPM2A 607566 MYOCLONIC EPILEPSY OF LAFORA #254780   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes HP:0000572 (Visual loss)
HP:0000992 (Photosensitivity)
Abdomen Liver HP:0001399 (Liver failure) (less common)
Neurologic Central Nervous System HP:0002123 (Myoclonic seizures), progressive
Generalized HP:0002069 (Tonic-clonic seizures)
HP:0002121 (Absence seizures)
Simple partial occipital seizures
Simple partial seizures with secondary generalization
HP:0001336 (myoclonus)
HP:0001268 (cognitive decline)
HP:0000726 (Dementia)
HP:0002186 (Apraxia)
Visual HP:0000738 (Hallucinations)
HP:0001288 (Gait disturbance)
HP:0002344 (Neurologic deterioration)
Disorganized EEG
Intracellular PAS-positive polyglucosan inclusion bodies ('Lafora' bodies)
Behavioral Psychiatric Manifestations HP:0000709 (Psychosis)
Laboratory Abnormalities - Intracellular PAS-positive polyglucosan inclusion bodies ('Lafora' bodies) can be found in various tissues (brain, liver, muscle, heart, skin)
Miscellaneous - Onset in late childhood/adolescence (approximately 15 years)
Short survival (less than 10 years after onset)
Rapidly HP:0003676 (Progressive disorder)
Genetic heterogeneity
Patients with mutation in the NHLRC1 gene have slightly longer survival
 
ERCC1 126380 CEREBROOCULOFACIOSKELETAL SYNDROME 4; COFS4 610758   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001511 (Intrauterine growth retardation)
HP:0001510 (Growth delay)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0000347 (Micrognathia)
HP:0000322 (Short philtrum)
Ears HP:0000369 (Low-set ears)
HP:0000358 (Posteriorly rotated ears)
Eyes HP:0000568 (Microphthalmia)
HP:0000581 (Blepharophimosis)
HP:0000490 (Deep-set eyes)
HP:0000639 (Nystagmus)
Nose HP:0000426 (High nasal bridge)
Skeletal - HP:0002804 (Arthrogryposis)
Joint HP:0004576 (large joint contractures)
Skull Premature closure of fontanels
Spine HP:0002751 (kyphoscoliosis)
Pelvis Sloping acetabulae
HP:0002827 (Hip dislocations)
Limbs HP:0003100 (Slender long bones)
HP:0003015 (Flared metaphyses)
Dislocated radial head
Hands HP:0100490 (Camptodactyly)
HP:0001181 (Adducted thumbs)
Feet HP:0001838 (Rocker-bottom feet)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
Stiff limbs
HP:0001276 (Muscle hypertonia)
Abnormal EEG
HP:0009879 (Simplified gyral pattern)
HP:0002126 (Polymicrogyria)
HP:0001321 (Cerebellar hypoplasia)
Peripheral Nervous System HP:0001347 (Hyperreflexia)
Laboratory Abnormalities - Patient cells show a defect in transcription-coupled and global genome nucleotide excision repair
Miscellaneous - HP:0003577 (Onset at birth)
Early death
HP:0003828 (Variable severity)
 
ERCC6 609413 COCKAYNE SYNDROME B; CSB 133540   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001511 (Intrauterine growth retardation)
HP:0001518 (Small for gestational age)
Marked HP:0001508 (Failure to thrive)
HP:0008897 (Postnatal growth retardation)
Cachectic HP:0003510 (short stature)
Head and Neck Head HP:0000252 (microcephaly)
Mandible HP:0000303 (Prognathism)
Face Loss of facial adipose tissue
HP:0005328 (Wizened face)
Ears HP:0000377 (Dysplastic ears)
HP:0000407 (sensorineural hearing loss)
Eyes HP:0000580 (Pigmentary retinopathy)
HP:0000648 (optic atrophy)
HP:0000486 (Strabismus)
HP:0000540 (Hypermetropia)
HP:0007957 (Corneal opacity)
HP:0000633 (Decreased lacrimation)
HP:0000639 (Nystagmus)
HP:0000518 (Cataracts)
HP:0000568 (Microphthalmia)
HP:0007676 (Iris hypoplasia)
HP:0000482 (Microcornea)
Nose Slender nose
Teeth HP:0000670 (Dental caries)
HP:0000680 (Delayed eruption of deciduous teeth)
HP:0000689 (Dental malocclusion)
Absent/HP:0000685 (Hypoplasia of teeth)
Cardiovascular Heart Cardiac HP:0011675 (Arrhythmias)
Vascular HP:0000822 (Hypertension)
Abdomen Liver HP:0002240 (Hepatomegaly)
Spleen HP:0001744 (Splenomegaly)
Genitourinary External Genitalia (Male) HP:0000054 (Small penis)
Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
Kidneys HP:0000093 (Proteinuria)
HP:0000083 (Renal failure)
Skeletal - HP:0000939 (Osteoporosis)
Skull Thickened calvarium
Spine HP:0002808 (Kyphosis)
Vertebral body abnormalities
Intervertebral calcifications
Pelvis Small, squared off pelvis
HP:0002866 (Hypoplastic iliac wings)
Limbs Mild to moderate HP:0001376 (joint limitation)
Hands Sclerotic ivory phalangeal epiphyses
Skin, Nails, Hair - Precociously senile appearance
Skin HP:0000992 (Photosensitivity)
Scarring
Pigmentation
Atrophy
HP:0000970 (Anhidrosis)
HP:0000958 (Dry skin)
Decreased subcutaneous adipose tissue
Hair Thin, dry hair
Muscle, Soft Tissue - HP:0003758 (Decreased subcutaneous adipose tissue)
Neurologic Central Nervous System HP:0001249 (Intellectual disability)
Normal pressure HP:0000238 (Hydrocephalus)
Poor-absent neurologic development
HP:0002135 (Basal ganglia calcification)
Subcortical white matter calcifications
HP:0007352 (Cerebellar calcifications)
Patchy HP:0007305 (CNS demyelination) of subcortical white matter
HP:0002283 (global brain atrophy)
Seizures
Peripheral Nervous System HP:0007266 (Dysmyelination)
HP:0001251 (ataxia)
HP:0002322 (Resting tremor)
HP:0003324 (Muscle weakness)
HP:0009830 (Peripheral neuropathy)
Slowed nerve conduction velocities
Laboratory Abnormalities - Abnormal myelination in sural nerve biopsies
Disturbed visual and brainstem auditory evoked responses indicative of CNS HP:0007305 (CNS demyelination)
Increased cellular sensitivity to UV light
Miscellaneous - Two types, type I or type A (classical Cockayne syndrome, 216400) and type II or type B (severe Cockayne syndrome, 133540)
Characteristic face and body by age 2 years
Death by age 6-7 years
Death from HP:0002090 (Pneumonia)
 
ERCC8 609412 COCKAYNE SYNDROME A; CSA 216400   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001511 (Intrauterine growth retardation)
Severe HP:0008897 (Postnatal growth retardation)
Cachectic HP:0003510 (short stature)
Head and Neck Head HP:0000252 (microcephaly)
Mandible HP:0000303 (Prognathism)
Face Loss of facial adipose tissue
HP:0005328 (Wizened face)
Ears HP:0000377 (Dysplastic ears)
HP:0000407 (sensorineural hearing loss)
Eyes Salt and pepper retinal pigmentation
HP:0000580 (Pigmentary retinopathy)
HP:0000648 (optic atrophy)
HP:0000486 (Strabismus)
HP:0000540 (Hypermetropia)
HP:0007957 (Corneal opacity)
HP:0000633 (Decreased lacrimation)
HP:0000639 (Nystagmus)
HP:0000518 (Cataracts)
Nose Slender nose
Teeth HP:0000670 (Dental caries)
HP:0000680 (Delayed eruption of deciduous teeth)
HP:0000689 (Dental malocclusion)
Absent/HP:0000685 (Hypoplasia of teeth)
Cardiovascular Heart Cardiac HP:0011675 (Arrhythmias)
Vascular HP:0000822 (Hypertension)
Abdomen Liver HP:0002240 (Hepatomegaly)
Spleen HP:0001744 (Splenomegaly)
Genitourinary External Genitalia (Male) HP:0000028 (Cryptorchidism)
HP:0000054 (Small penis)
Kidneys HP:0000093 (Proteinuria)
HP:0000083 (Renal failure)
Skeletal Skull Thickened calvarium
Spine HP:0002808 (Kyphosis)
Vertebral body abnormalities
Pelvis Small, squared off pelvis
HP:0002866 (Hypoplastic iliac wings)
Limbs Mild to moderate HP:0001376 (joint limitation)
Hands Sclerotic ivory phalangeal epiphyses
Skin, Nails, Hair - Precociously senile appearance
Skin HP:0000992 (Photosensitivity)
Scarring
Pigmentation
Atrophy
HP:0000970 (Anhidrosis)
HP:0000958 (Dry skin)
Decreased subcutaneous adipose tissue
Hair Thin, dry hair
Muscle, Soft Tissue - Decreased subcutaneous adipose tissue
Neurologic Central Nervous System HP:0001249 (Intellectual disability)
Normal pressure HP:0000238 (Hydrocephalus)
HP:0000726 (Dementia)
HP:0002135 (Basal ganglia calcification)
Patchy HP:0007305 (CNS demyelination) of subcortical white matter
Seizures
HP:0002283 (global brain atrophy)
Dysarthric speech
Peripheral Nervous System HP:0007266 (Dysmyelination)
HP:0001288 (Gait disturbance)
HP:0001251 (ataxia)
HP:0002322 (Resting tremor)
HP:0003324 (Muscle weakness)
HP:0009830 (Peripheral neuropathy)
Slowed nerve conduction velocities
Endocrine Features - Irregular menstrual cycles
HP:0000815 (Hypogonadism)
Laboratory Abnormalities - Thymic hormone decreased
At least 2 complementation groups
Abnormal myelination in sural nerve biopsies
Disturbed visual and brainstem auditory evoked responses indicative of CNS HP:0007305 (CNS demyelination)
Increased cellular sensitivity to UV light
Miscellaneous - Phenotypic overlap with xeroderma pigmentosum (see, e.g., 278700)
Genetic heterogeneity (see, e.g., Cockayne syndrome type B, 133540)
 
ERLIN2 611605 SPASTIC PARAPLEGIA 18, AUTOSOMAL RECESSIVE; SPG18 611225   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes HP:0000486 (Strabismus)
HP:0000617 (Abnormal smooth pursuit)
Mouth HP:0000218 (High-arched palate)
Skeletal - HP:0004576 (large joint contractures), progressive, severe
Spine HP:0002650 (Scoliosis)
HP:0002808 (Kyphosis)
Feet HP:0001761 (Pes cavus)
Muscle, Soft Tissue - Lower limb HP:0003324 (Muscle weakness)
Global HP:0003324 (Muscle weakness)
HP:0003202 (Muscle atrophy)
HP:0001276 (Hypertonicity)
Neurologic Central Nervous System Delayed walking
HP:0001288 (Gait disturbance)
Lower limb HP:0001257 (Spasticity)
Upper limb HP:0001257 (Spasticity), mild
HP:0003487 (Extensor plantar responses)
HP:0001347 (Hyperreflexia)
HP:0001344 (absent speech)
HP:0001249 (Intellectual disability) (in most patients)
Seizures (in some patients)
Miscellaneous - HP:0003593 (Onset in infancy) or childhood (range 1 to 6 years)
Regression in infancy (in some patients)
HP:0003676 (Progressive disorder)
Results in severe motor disability and loss of independent ambulation
 
ERMARD 615532 PERIVENTRICULAR NODULAR HETEROTOPIA 6; PVNH6 615544   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Eyes HP:0000486 (Strabismus)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
Seizures
HP:0000750 (language delay
HP:0002521 (hypsarrhythmia)
Periventricular nodular HP:0002282 (heterotopia)
 
ESCO2 609353 SC PHOCOMELIA SYNDROME 269000   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Other HP:0001511 (Intrauterine growth retardation)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0000347 (Micrognathia)
Ears HP:0000358 (Posteriorly rotated ears)
Absent lobules
Eyes HP:0000592 (Bluish sclerae)
Nose HP:0000430 (Hypoplastic nasal alae)
Mouth HP:0100333 (Unilateral cleft lip)
Cardiovascular Heart HP:0001650 (Aortic stenosis)
Skeletal Skull HP:0002645 (Wormian bones)
Pelvis Hip HP:0004576 (large joint contractures)
Limbs HP:0003974 (HP:0004977 (radial aplasia) and ulna)
Knee HP:0004576 (large joint contractures)
Hands HP:0009778 (Small thumbs)
HP:0004209 (Fifth finger clinodactyly)
Skin, Nails, Hair Skin Midface capillary HP:0001028 (Hemangioma)
Hair Silvery-blond hair
HP:0008070 (Sparse hair)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
Seizures
Laboratory Abnormalities - Premature separation of centromeric heterochromatin
Miscellaneous - Allelic to Roberts syndrome (268300)
 
ETFA 608053 MULTIPLE ACYL-CoA DEHYDROGENASE DEFICIENCY; MADD #231680   3 GU HP:0000114 (Proximal tubulopathy)
Renal cortical cysts
HP:0000113 (Polycystic kidneys)
Genital defects
Respiratory HP:0002098 (Respiratory distress)
HP:0004971 (Pulmonary hypoplasia)
Neuro HP:0001325 (Hypoglycemic coma)
HP:0003324 (Muscle weakness)
Muscular HP:0008947 (Hypotonia, early)
Lab Glutaric aciduria
Glutaric acidemia
Ethylmalonic aciduria
HP:0003076 (Glucosuria)
Generalized HP:0003355 (Aminoaciduria)
Defective dehydrogenation of isovaleryl CoA and butyryl CoA
Electron transfer flavoprotein-ubiquinone oxidoreductase defect
Inheritance HP:0000007 (Autosomal recessive)
Metabolic Neonatal acidosis
HP:0001943 (Hypoglycemia)
HEENT HP:0001999 (Dysmorphic features)
HP:0000256 (Macrocephaly)
Cerebral HP:0001302 (pachygyria)
Cerebral HP:0002171 (Gliosis)
HP:0000260 (Wide anterior fontanel)
HP:0000348 (High forehead)
HP:0000431 (Broad nasal bridge)
HP:0000506 (telecanthus)
Congenital HP:0000518 (Cataracts)
HP:0000377 (Dysplastic ears)
Skin HP:0000952 (Jaundice)
Misc Sweaty feet odor
Stale breath odor
Neonatal death frequent
GI HP:0002018 (Nausea)
HP:0002013 (Vomiting)
HP:0001397 (Fatty infiltration of liver)
HP:0002240 (Hepatomegaly)
Hepatic periportal necrosis
Neonatal acidosis
Hypoglycemia
Glutaric aciduria
Glutaric acidemia
Ethylmalonic aciduria
ETFB 130410 MULTIPLE ACYL-CoA DEHYDROGENASE DEFICIENCY; MADD #231680   3 GU HP:0000114 (Proximal tubulopathy)
Renal cortical cysts
HP:0000113 (Polycystic kidneys)
Genital defects
Respiratory HP:0002098 (Respiratory distress)
HP:0004971 (Pulmonary hypoplasia)
Neuro HP:0001325 (Hypoglycemic coma)
HP:0003324 (Muscle weakness)
Muscular HP:0008947 (Hypotonia, early)
Lab Glutaric aciduria
Glutaric acidemia
Ethylmalonic aciduria
HP:0003076 (Glucosuria)
Generalized HP:0003355 (Aminoaciduria)
Defective dehydrogenation of isovaleryl CoA and butyryl CoA
Electron transfer flavoprotein-ubiquinone oxidoreductase defect
Inheritance HP:0000007 (Autosomal recessive)
Metabolic Neonatal acidosis
HP:0001943 (Hypoglycemia)
HEENT HP:0001999 (Dysmorphic features)
HP:0000256 (Macrocephaly)
Cerebral HP:0001302 (pachygyria)
Cerebral HP:0002171 (Gliosis)
HP:0000260 (Wide anterior fontanel)
HP:0000348 (High forehead)
HP:0000431 (Broad nasal bridge)
HP:0000506 (telecanthus)
Congenital HP:0000518 (Cataracts)
HP:0000377 (Dysplastic ears)
Skin HP:0000952 (Jaundice)
Misc Sweaty feet odor
Stale breath odor
Neonatal death frequent
GI HP:0002018 (Nausea)
HP:0002013 (Vomiting)
HP:0001397 (Fatty infiltration of liver)
HP:0002240 (Hepatomegaly)
Hepatic periportal necrosis
Neonatal acidosis
Hypoglycemia
Glutaric aciduria
Glutaric acidemia
Ethylmalonic aciduria
ETFDH 231675 MULTIPLE ACYL-CoA DEHYDROGENASE DEFICIENCY; MADD #231680   3 GU HP:0000114 (Proximal tubulopathy)
Renal cortical cysts
HP:0000113 (Polycystic kidneys)
Genital defects
Respiratory HP:0002098 (Respiratory distress)
HP:0004971 (Pulmonary hypoplasia)
Neuro HP:0001325 (Hypoglycemic coma)
HP:0003324 (Muscle weakness)
Muscular HP:0008947 (Hypotonia, early)
Lab Glutaric aciduria
Glutaric acidemia
Ethylmalonic aciduria
HP:0003076 (Glucosuria)
Generalized HP:0003355 (Aminoaciduria)
Defective dehydrogenation of isovaleryl CoA and butyryl CoA
Electron transfer flavoprotein-ubiquinone oxidoreductase defect
Inheritance HP:0000007 (Autosomal recessive)
Metabolic Neonatal acidosis
HP:0001943 (Hypoglycemia)
HEENT HP:0001999 (Dysmorphic features)
HP:0000256 (Macrocephaly)
Cerebral HP:0001302 (pachygyria)
Cerebral HP:0002171 (Gliosis)
HP:0000260 (Wide anterior fontanel)
HP:0000348 (High forehead)
HP:0000431 (Broad nasal bridge)
HP:0000506 (telecanthus)
Congenital HP:0000518 (Cataracts)
HP:0000377 (Dysplastic ears)
Skin HP:0000952 (Jaundice)
Misc Sweaty feet odor
Stale breath odor
Neonatal death frequent
GI HP:0002018 (Nausea)
HP:0002013 (Vomiting)
HP:0001397 (Fatty infiltration of liver)
HP:0002240 (Hepatomegaly)
Hepatic periportal necrosis
Neonatal acidosis
Hypoglycemia
Glutaric aciduria
Glutaric acidemia
Ethylmalonic aciduria
ETHE1 608451 ENCEPHALOPATHY, ETHYLMALONIC; EE #602473   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Eyes Retinal lesions with tortuous vessels
Cardiovascular Vascular Orthostatic HP:0000961 (Cyanosis)
Abdomen Gastrointestinal Chronic HP:0002014 (Diarrhea)
Skin, Nails, Hair Skin HP:0000967 (Petechiae)
Orthostatic HP:0000961 (Cyanosis)
Neurologic Central Nervous System HP:0002376 (Psychomotor regression)
HP:0012758 (neurodevelopmental delay)
HP:0001249 (Intellectual disability)
HP:0007256 (Pyramidal signs)
HP:0002071 (Extrapyramidal signs)
HP:0001251 (ataxia)
HP:0008947 (Hypotonia, early)
Seizures
HP:0007183 (Hyperintense lesions in the basal ganglia on MRI)
Laboratory Abnormalities - HP:0003128 (Lactic acidosis)
Ethylmalonic aciduria
Methylsuccinic aciduria
Cytochrome c oxidase deficiency in skeletal muscle and brain
Increased serum C4 and C5 acylcarnitine esters
Increased urinary isobutyryl glycine
Increased urinary 2-methylbutyryl glycine
Increased urinary thiosulphate
Miscellaneous - Onset in first months of life
Patients are often of Mediterranean origin
Death usually occurs in first decade of life
Lactic acidosis
Ethylmalonic aciduria
Methylsuccinic aciduria
Increased C4 and C5 acylcarnitine esters (P)
Increased isobutyryl glycine (U)
Increased 2-methylbutyryl glycine (U)
Increased thiosulphate (U)
EXOSC3 606489 PONTOCEREBELLAR HYPOPLASIA, TYPE 1B; PCH1B 614678   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001510 (Growth delay), postnatal
Head and Neck Head HP:0000252 (microcephaly), postnatal, progressive (-2 to -3.5 SD)
HP:0002421 (Poor head control)
Eyes HP:0000657 (Oculomotor apraxia)
HP:0000639 (Nystagmus)
Poor visual attention
HP:0000486 (Strabismus)
HP:0000556 (Retinal dystrophy) (1 family)
Mouth HP:0012473 (Tongue atrophy)
Tongue HP:0002380 (Fasciculations)
Respiratory - HP:0002093 (Respiratory insufficiency)
Abdomen Gastrointestinal HP:0011968 (feeding difficulties)
Skeletal - Joint HP:0004576 (large joint contractures)
Pelvis HP:0002827 (Hip dislocations)
Feet HP:0001760 (Foot deformities)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
HP:0003324 (Muscle weakness)
HP:0003202 (Muscle atrophy)
EMG shows neurogenic changes
Neurologic Central Nervous System Global HP:0012758 (neurodevelopmental delay), HP:0003828 (Variable severity)
Lack of motor milestones
Axial HP:0008947 (Hypotonia, early)
HP:0001257 (Spasticity)
HP:0001347 (Hyperreflexia)
HP:0001344 (absent speech)
HP:0002283 (global brain atrophy)
HP:0001272 (Cerebellar atrophy)
HP:0002350 (Cerebellar cysts)
Seizures (in some patients)
Atrophy of the pons (in some patients)
Loss of cerebellar Purkinje cells
Loss of cerebellar granular cells
Loss of motor neurons in the spinal cord
Peripheral Nervous System Axonal motor neuropathy
Miscellaneous - HP:0003577 (Onset at birth)
Early death may occur
HP:0003828 (Variable severity)
 
EZH2 601573 WEAVER SYNDROME; WVS 277590   2 Inheritance - HP:0000006 (Autosomal dominant)
Growth Height Increased prenatal/postnatal length
Weight Increased prenatal/postnatal weight
Weight more increased than height
Head and Neck Head HP:0000256 (Macrocephaly)
Large bifrontal diameter
HP:0005469 (Flat occiput)
Face HP:0000343 (Long philtrum)
HP:0000311 (Round face) in infancy
HP:0000278 (Retrognathia)
HP:0000303 (Mandibular prognathia) crease
Ears HP:0000400 (macrotia)
Eyes HP:0000486 (Strabismus)
HP:0000316 (Hypertelorism)
HP:0000286 (Epicanthus)
HP:0000494 (Downslanting palpebral fissures)
Nose HP:0005280 (depressed nasal bridge)
Chest Ribs, Sternum, Clavicles and Scapulae HP:0000773 (Short ribs)
Breasts HP:0003186 (Inverted nipples)
Abdomen External Features HP:0001537 (Umbilical hernia)
HP:0001540 (Diastasis recti)
Excessive appetite
Genitourinary External Genitalia (Male) HP:0000023 (Inguinal hernia)
HP:0000034 (Hydrocele)
Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
Skeletal - HP:0005616 (Advanced bone age)
Dysharmonic bone age (carpals more advanced than phalanges)
Spine HP:0002650 (Scoliosis)
HP:0002808 (Kyphosis)
Pelvis HP:0002866 (Small iliac wings)
HP:0002673 (Coxa valga)
Limbs Limited elbow extension
Limited knee extension
HP:0003015 (Flared metaphyses) (especially distal femora and humeri)
Hands HP:0100490 (Camptodactyly)
HP:0011304 (Broad thumbs)
Prominent fingertip pads
HP:0001176 (Large hands)
HP:0004209 (Fifth finger clinodactyly)
Carpal bone development advanced over that of other hand bones
Feet HP:0001762 ( Pes equinovarus)
HP:0001848 (Pes calcaneovalgus)
HP:0001840 (Metatarsus adductus)
Short fourth metatarsals
Prominent toe pads
HP:0001761 (Pes cavus)
HP:0004209 (Fifth finger clinodactyly)
HP:0001845 (Overriding toes)
Skin, Nails, Hair Skin Loose skin
Increased pigmented nevi
Nails Thin, deep-set nails
Hair Thin hair
Neurologic Central Nervous System HP:0000750 (Speech delay)
HP:0001260 (Dysarthria)
HP:0001350 (Slurred speech)
HP:0012758 (neurodevelopmental delay)
HP:0001249 (Intellectual disability)
HP:0001276 (Muscle hypertonia)
HP:0001257 (Spasticity)
HP:0008947 (Hypotonia, early)
HP:0002069 (tonic-clonic seizures) or absence (in some patients)
HP:0001331 (Absence of septum pellucidum)
Lateral ventricle dilatation
HP:0000708 (behavioral disturbance)
Voice - Coarse, low-pitched voice
Miscellaneous - Most cases are HP:0003745 (sporadic)
Significant clinical overlap with Sotos syndrome (117550)
 
FA2H 611026 SPASTIC PARAPLEGIA 35, AUTOSOMAL RECESSIVE; SPG35 #612319   5 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes External HP:0000544 (Ophthalmoplegia) (less common)
HP:0000648 (optic atrophy)
HP:0000639 (Nystagmus)
HP:0000486 (Strabismus)
Genitourinary Bladder HP:0000012 (Urinary urgency)
Incontinence (variable)
Neurologic Central Nervous System HP:0001257 (Spasticity), primarily lower limbs, but upper limbs may be involved
HP:0001288 (Gait disturbance)
Spastic HP:0002273 (Quadriplegia)
HP:0001251 (ataxia)
HP:0001347 (Hyperreflexia)
HP:0007325 (generalized dystonia)
HP:0001260 (Dysarthria)
HP:0001310 (Dysmetria)
HP:0001268 (cognitive decline)
HP:0001249 (Intellectual disability)
HP:0003487 (Extensor plantar responses)
Seizures
HP:0002079 (Hypoplasia of the corpus callosum)
HP:0007366 (Brainstem atrophy)
HP:0001272 (Cerebellar atrophy)
HP:0002415 (Leukodystrophy), dysmyelinating
Periventricular HP:0002500 (White matter abnormalities)
White matter hyperintensities in T2 imaging
Iron deposition in the globus pallidus (variable)
Miscellaneous - Onset between 3 and 11 years of age
HP:0003676 (Progressive disorder)
Most patients become wheelchair-bound in adolescence or as young adults
0
FADD 602457 INFECTIONS, RECURRENT, WITH ENCEPHALOPATHY, HEPATIC DYSFUNCTION, AND CARDIOVASCULAR MALFORMATIONS #613759   2 Inheritance - HP:0000007 (Autosomal recessive)
Cardiovascular Heart HP:0001629 (Ventricular septal defect)
Vascular Superior vena cava left-sided, draining into left atrium
HP:0010882 (Pulmonary atresia)
Abdomen Liver HP:0001410 (Liver dysfunction), mild
Transaminases mildly elevated
Spleen Functional hyposplenism
Howell-Jolly bodies present
Neurologic Central Nervous System HP:0004319 (nonprogressive encephalopathy)
HP:0002283 (global brain atrophy)
Seizures
Immunology - HP:0002783 (Recurrent infections)
Increased number of CD4(-)CD8(-)TCR-alpha-beta(+) T cells
Laboratory Abnormalities - Increased Fas ligand
Increased interleukin 10
 
FAM111A 615292 KENNY-CAFFEY SYNDROME, TYPE 2; KCS2 127000   2 Inheritance - HP:0000006 (Autosomal dominant)
Growth Height HP:0004322 (short stature), severe
Weight HP:0001518 (Small for gestational age)
Head and Neck Head HP:0000256 (Macrocephaly)
Face HP:0011220 (Prominent forehead)
Eyes HP:0000540 (Hypermetropia)
HP:0000568 (Microphthalmia)
HP:0001085 (Papilledema)
Corneal and retinal calcification
Congenital HP:0000518 (Cataracts) (rare)
Teeth Defective dentition (in some patients)
Genitourinary External Genitalia (Male) HP:0008734 (small testes)
Skeletal - HP:0005789 (Osteosclerosis)
Thickened cortex of long bones
Dense tubular bones and narrow marrow cavities
Skull Delayed closure of anterior fontanel
HP:0000256 (Macrocephaly)
Neurologic Central Nervous System Normal intelligence
HP:0001281 (Tetany), hypocalcemic, episodic
HP:0002135 (Basal ganglia calcification)
Seizures
Voice - HP:0001620 (High-pitched voice) (in some patients)
Endocrine Features - HP:0000829 (Hypoparathyroidism)
Low calcitonin
Small to absent parathyroid glands
Hematology - HP:0001903 (Anemia) (in some patients)
Laboratory Abnormalities - HP:0002901 (hypocalcemia), transient
HP:0002905 (Hyperphosphatemia), transient
 
FAM126A 610531 LEUKODYSTROPHY, HYPOMYELINATING, 5; HLD5 #610532   5 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes HP:0000518 (Cataracts), usually congenital
Skeletal Spine HP:0002650 (Scoliosis), progressive
Muscle, Soft Tissue - HP:0003324 (Muscle weakness) and wasting of the lower limbs
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay) (apparent after the first year of life)
HP:0001270 (Delayed motor development)
HP:0002540 (inability to walk) independently
HP:0002505 (Progressive inability to walk) later
HP:0001260 (Dysarthria)
Truncal HP:0008947 (Hypotonia, early)
HP:0001347 (Hyperreflexia)
HP:0003487 (Extensor plantar responses)
HP:0007256 (Pyramidal tract signs)
HP:0001249 (Intellectual disability), mild to moderate
Seizures (less common)
Intention HP:0002322 (Resting tremor)
Truncal titubation
HP:0001317 (Cerebellar signs)
HP:0002415 (Leukodystrophy), hypomyelinating
Cerebral white matter atrophy, progressive
Peripheral Nervous System HP:0009830 (Peripheral neuropathy)
Decreased motor nerve conduction velocities
Sural nerve biopsy shows decrease in myelinated fibers
Loss of myelin
Abnormal folding of the myelin sheath
Small onion bulb formation
Miscellaneous - HP:0003593 (Onset in infancy)
HP:0003828 (Variable severity)
 
FAR1 616107 PEROXISOMAL FATTY ACYL-CoA REDUCTASE 1 DISORDER; PFCRD #616154   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0008897 (Postnatal growth retardation)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0001999 (Dysmorphic facial features), mild
HP:0000280 (Coarse facies)
HP:0000343 (Long philtrum)
Ears HP:0000400 (macrotia)
Eyes HP:0000518 (Cataracts)
High-HP:0002553 (Arched eyebrows)
Nose HP:0005280 (Depressed nasal bridge)
Mouth HP:0000219 (Thin upper lip)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development), severe
HP:0001249 (Intellectual disability)
HP:0001257 (Spasticity)
Seizures
HP:0001272 (Cerebellar atrophy)
Cerebral white matter lesions
Laboratory Abnormalities - Decreased plasmalogen
Miscellaneous - Onset in early infancy
Decreased plasmalogen
FARS2 611592 COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 14; COXPD14 #614946   1 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001510 (Growth delay)
Head and Neck Head HP:0000252 (microcephaly)
Ears Hearing impairment (rare)
Eyes Coarse retinal pigmentation (rare)
HP:0000505 (Visual impairment) (rare)
Abdomen Liver Enlarged hepatocytes (rare)
Increased glycogen content (rare)
Gastrointestinal HP:0011968 (feeding difficulties)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Deficiency of mitochondrial respiratory enzymes seen on muscle biopsy
Neurologic Central Nervous System Global HP:0012758 (neurodevelopmental delay), profound
Seizures, refractory
HP:0001336 (myoclonus)
Abnormal EEG
Diffuse HP:0002283 (global brain atrophy) seen on MRI
HP:0002119 (ventriculomegaly)
T2-weighted hyperintensities in the basal ganglia
Leigh syndrome
HP:0002283 (global brain atrophy)
Cortical degeneration
Decreased pyramidal cells
Laminar necrosis
Microcystic degeneration
Reactive HP:0002171 (Gliosis)
HP:0001272 (Cerebellar atrophy)
HP:0007366 (Brainstem atrophy)
Metabolic Features - HP:0003128 (Lactic acidosis)
Hematology - HP:0001903 (Anemia) (rare)
HP:0001873 (thrombocytopenia) (rare)
Laboratory Abnormalities - HP:0002151 (Increased serum lactate)
HP:0003355 (Aminoaciduria) (rare)
Miscellaneous - Onset in early infancy
HP:0001522 (Death in infancy)
Lactic acidosis
FASN 600212 Epileptic encephalopathy   25262651 2 0 0
FASTKD2 612322 MITOCHONDRIAL COMPLEX IV DEFICIENCY 220110   2 Inheritance - HP:0000007 (Autosomal recessive)
Mitochondrial
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Ears HP:0000407 (sensorineural hearing loss)
Eyes HP:0000648 (optic atrophy)
HP:0000580 (Pigmentary retinopathy)
HP:0000508 (Ptosis)
Cardiovascular Heart HP:0001639 (hypertrophic cardiomyopathy)
Respiratory - HP:0002880 (Respiratory difficulties)
HP:0002878 (Respiratory failure) due to HP:0003324 (Muscle weakness)
Exertional HP:0002094 (dyspnea)
Abdomen Liver HP:0001410 (Liver dysfunction)
HP:0002240 (Hepatomegaly)
Liver biopsy shows increased lipid droplets and HP:0012103 (Abnormality of the mitochondrion)
Genitourinary Kidneys HP:0001994 (Renal Fanconi syndrome)
HP:0000124 (Renal tubular dysfunction)
Biopsy shows decreased cytochrome c oxidase
Muscle, Soft Tissue - HP:0003324 (Muscle weakness)
HP:0008947 (Hypotonia, early)
HP:0003546 (Exercise intolerance)
Muscle biopsy shows decrease or absence of cytochrome c oxidase
Increased lipid droplets and HP:0012103 (Abnormality of the mitochondrion)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
HP:0001270 (Delayed motor development)
HP:0008947 (Hypotonia, early)
HP:0001251 (ataxia)
HP:0007256 (pyramidal tract signs)
Seizures
HP:0001249 (Intellectual disability)
HP:0002490 (Increased CSF lactate)
Symmetric lesions in the basal ganglia consistent with Leigh syndrome (256000), in a subset of patients
Metabolic Features - HP:0003128 (Lactic acidosis)
Hematology - HP:0001903 (Anemia) (associated with mutation in the COX10 gene)
Laboratory Abnormalities - HP:0002151 (Increased serum lactate)
HP:0002490 (Increased CSF lactate)
HP:0000093 (Proteinuria)
HP:0003076 (Glucosuria)
HP:0003355 (Aminoaciduria)
HP:0003109 (Hyperphosphaturia)
Decreased activity of cytochrome c oxidase in muscle and fibroblasts
Miscellaneous - Marked clinical heterogeneity
Symptom onset ranges from infancy to adulthood
Death may occur in infancy
Genetic heterogeneity (may be caused by mutation in nuclear-encoded or mitochondrial-encoded genes)
Subset of patients have Leigh syndrome (256000)
Subset of patients have French-Canadian Leigh syndrome (220111)
Increased lactate (P, C)
FBP1 611570 FRUCTOSE-1,6-BISPHOSPHATASE DEFICIENCY; FBP1D 229700   3 Inheritance - HP:0000007 (Autosomal recessive)
Cardiovascular Heart HP:0001649 (Tachycardia)
Respiratory - HP:0002104 (Apnea)
HP:0002094 (dyspnea)
HP:0002883 (Hyperventilation)
Abdomen Liver HP:0002240 (Hepatomegaly)
Neurologic Central Nervous System HP:0008947 (Hypotonia, early)
HP:0001254 (Lethargy)
Seizures
Coma
Behavioral Psychiatric ManifestationsHP:0000737 (Irritability)
Metabolic Features - HP:0001942 (metabolic acidosis)
HP:0001943 (Hypoglycemia)
HP:0001946 (Ketosis)
Laboratory Abnormalities - Increased urinary glycerol
Decreased FBP1 enzyme activity
Miscellaneous - Onset in newborns or infants
Episodes triggered by fasting, illness, HP:0001945 (Fever)
Patients show sorbitol and glycerol intolerance
Metabolic acidosis
Hypoglycemia
Increased glycerol (U)
FBXL4 605654 MITOCHONDRIAL DNA DEPLETION SYNDROME 13 (ENCEPHALOMYOPATHIC TYPE); MTDPS13 #615471   5 Inheritance - HP:0000007 (Autosomal recessive)
Growth Weight HP:0001518 (Small for gestational age)
Other HP:0001508 (Failure to thrive)
HP:0001510 (Growth delay)
Head and Neck Head HP:0000252 (microcephaly) (in some patients)
HP:0001357 (Plagiocephaly) (in some patients)
Face HP:0001999 (Dysmorphic facial features), variable (in some patients)
HP:0000275 (narrow face)
HP:0000276 (long face)
Ears HP:0000377 (Dysplastic ears)
HP:0000411 (Prominent ears)
Eyes HP:0000518 (Cataracts) (in some patients)
HP:0000639 (Nystagmus) (in some patients)
HP:0000286 (Epicanthus)
HP:0000494 (Downslanting palpebral fissures)
HP:0000574 (Thick eyebrows)
Nose HP:0011120 (Saddle nose)
Mouth HP:0000179 (Thick lower lip vermilion)
Cardiovascular Heart HP:0001639 (hypertrophic cardiomyopathy) (uncommon)
Arrhythmia (uncommon)
Abdomen Gastrointestinal HP:0002020 (Gastroesophageal reflux) disease
HP:0002015 (Dysphagia)
Genitourinary External Genitalia (Male) HP:0000047 (Hypospadias)
Kidneys HP:0001947 (Renal tubular acidosis) (in some patients)
Skeletal Spine HP:0002650 (Scoliosis) (in some patients)
Feet HP:0001773 (Small feet)(in some patients)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
HP:0003202 (Muscle atrophy)
Neurologic Central Nervous System HP:0004319 (nonprogressive encephalopathy)
Global HP:0012758 (neurodevelopmental delay), severe
Seizures
HP:0001251 (ataxia) (in some patients)
HP:0007325 (generalized dystonia) (in some patients)
HP:0001266 (Choreoathetosis) (in some patients)
HP:0002283 (global brain atrophy)
HP:0002415 (Leukodystrophy)
HP:0001272 (Cerebellar atrophy) (in some patients)
HP:0002500 (White matter abnormalities)
HP:0012448 (Delayed myelination)
HP:0002079 (Thin corpus callosum)
Brainstem white matter lesions
White matter lesions in the basal ganglia
Metabolic Features - HP:0003128 (Lactic acidosis)
Hematology - HP:0001875 (Neutropenia) (in some patients)
Immunology - HP:0002783 (Recurrent infections) (in some patients)
Laboratory Abnormalities - HP:0200125 (Mitochondrial respiratory chain defects) (skeletal muscle, fibroblasts)
Depletion of mtDNA (skeletal muscle, fibroblasts)
Fragmentation of the mitochondrial network
HP:0002151 (Increased serum lactate)
HP:0001987 (Hyperammonemia)
Increased serum alanine
HP:0002910 (HP:0002910 (abnormal liver enzymes) tests) (in some patients)
Miscellaneous - HP:0003577 (Onset at birth) or early infancy
HP:0003812 (Variable phenotype)
May result in early death
Lactic acidosis
FBXO28 609100 Intellectual disability and seizures   24357076 2 0  
FGFR1 136350 ENCEPHALOCRANIOCUTANEOUS LIPOMATOSIS; ECCL 613001   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Head HP:0000252 (microcephaly)
Ears HP:0000369 (Low-set ears)
HP:0000358 (Posteriorly rotated ears)
Eyes HP:0000286 (Epicanthus)
HP:0000316 (Hypertelorism)
HP:0000601 (Hypotelorism)
Nose HP:0000445 (Broad nose)
Mouth HP:0100333 (Unilateral cleft lip)
HP:0000175 (Cleft palate)
Genitourinary External Genitalia (Male) HP:0000054 (Small penis)
HP:0000047 (Hypospadias)
Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
Skeletal Skull HP:0005466 (Hypoplastic frontal bones)
HP:0011324 (multisutural craniosynostosis)
Hands HP:0100257 (Ectrodactyly)
HP:0006101 (Finger syndactyly)
Feet HP:0100257 (Ectrodactyly)
HP:0006101 (Finger syndactyly)
Neurologic Central Nervous System Lobar HP:0001360 (holoprosencephaly)
HP:0008947 (Hypotonia, early), neonatal
HP:0001263 (global developmental delay), severe
Vermian hypoplasia
HP:0001274 (agenesis of corpus callosum)
Endocrine Features - Gonadotropin deficiency
HP:0000873 (Diabetes insipidus)
Laboratory Abnormalities - HP:0003228 (Hypernatremia)
 
FGFR2 176943 CROUZON SYNDROME 123500   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Head HP:0011324 (multisutural craniosynostosis)
HP:0000248 (Brachycephaly)
Face HP:0002007 (Frontal bossing)
HP:0000327 (Hypoplasia of maxilla)
Mandibular HP:0000303 (Prognathism)
Ears ConductiveHP:0000410 (Hearing loss, mixed)
HP:0000413 (Atresia of the external auditory canal)
Eyes HP:0000648 (optic atrophy)
HP:0000586 (Shallow orbits)
HP:0000520 (Proptosis)
HP:0000316 (Hypertelorism)
HP:0000486 (Strabismus)
Exposure HP:0000509 (Conjunctivitis)/HP:0000491 (keratitis)
HP:0000505 (Visual impairment)
Nose Parrot-like nose
Mouth Lateral palatal swellings
Teeth HP:0000678 (Dental crowding)
Respiratory Nasopharynx HP:0010535 (sleep apnea)
Skeletal Skull HP:0011324 (multisutural craniosynostosis) (coronal, sagittal, lambdoid sutures)
Calcification of stylohyoid ligament
Spine Cervical spine abnormalities
Neurologic Central Nervous System HP:0001249 (Intellectual disability), occasional
Seizures
Frequent headaches
Miscellaneous - Associated with increased paternal age
 
FGFR3 134934 ACHONDROPLASIA, SEVERE, WITH DEVELOPMENTAL DELAY AND ACANTHOSIS NIGRICANS; SADDAN 616482   4 Inheritance - HP:0000006 (Autosomal dominant)
Growth Height HP:0003510 (short stature), lethal micromelic
Other Severe growth deficiency in survivors
Head and Neck Head HP:0002007 (Frontal bossing)
HP:0000256 (Macrocephaly)
Face HP:0000274 (Small face)
Respiratory Lung HP:0002093 (Respiratory insufficiency)/failure
Chest External Features HP:0000774 (Narrow chest)
Ribs, Sternum, Clavicles and Scapulae Wide-cupped costochondral junctions
Small abnormally formed scapulae
HP:0000773 (Short ribs)
Skeletal Skull HP:0002677 (Small foramen magnum)
HP:0002676 (Cloverleaf skull) rarely
Spine Severe HP:0000926 (Platyspondyly)
Pelvis Short and small iliac bones
Small sacroiliac notches
Limbs Marked shortness and bowing of long bones
'French telephone receiver femurs'
Flared and HP:0003025 (irregular metaphyses)
Neurologic Central Nervous System Temporal lobe HP:0002282 (heterotopia)s
HP:0000238 (Hydrocephalus)
Profound HP:0001249 (Intellectual disability) and HP:0008947 (Hypotonia, early) in survivors
Prenatal Manifestations - Prenatal diagnosis by ultrasound
Movement HP:0001558 (Decreased fetal movement)
Amniotic Fluid HP:0001561 (Polyhydramnios)
Miscellaneous - Death in majority of infants soon after birth
 
FH 136850 FUMARASE DEFICIENCY; FMRD #606812   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000256 (Macrocephaly), relative
Face HP:0002007 (Frontal bossing)
Eyes HP:0000316 (Hypertelorism)
HP:0000543 (Optic disc pallor)
HP:0000648 (optic atrophy)
HP:0000505 (Visual impairment)
Nose HP:0005280 (depressed nasal bridge)
HP:0000463 (Anteverted nares)
Mouth HP:0000218 (High-arched palate)
Abdomen Liver HP:0001399 (Liver failure)
HP:0001396 (Cholestasis)
Fibrosis
Iron deposition
Abnormal swollen mitochondria with flat, haphazardly arranged cristae
Skin, Nails, Hair Skin Cutaneous leiomyomata (heterozygote carriers)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
HP:0003199 (Decreased muscle mass)
HP:0001002 (Decreased subcutaneous fat)
Neurologic Central Nervous System HP:0001249 (Intellectual disability), profound
HP:0012758 (neurodevelopmental delay)
HP:0001344 (absent language)
HP:0002283 (global brain atrophy)
Seizures
HP:0002133 (Status epilepticus)
HP:0008947 (Hypotonia, early)
Most patients do not achieve independent sitting or walking
HP:0002119 (Ventriculomegaly)
HP:0002126 (Polymicrogyria)
Open operculum
Choroid plexus cysts
Decreased white matter volume
Angulation of the frontal horns
Small brainstem
HP:0001274 (agenesis of corpus callosum)
Metabolic Features - HP:0001942 (metabolic acidosis)
Hematology - HP:0001901 (Polycythemia), neonatal
HP:0003256 (Coagulopathy) in those with HP:0001399 (Liver failure)
Laboratory Abnormalities - HP:0003128 (Lactic acidosis)
Pyruvic acidemia
Fumaric aciduria
Fumarase activity (mitochondrial and cytosolic) is decreased
Increased urinary citric acid cycle intermediates
Increased urinary fumaric acid
Increased urinary malic acid
Increased urinary succinic acid
HP:0002904 (Hyperbilirubinemia) in those with HP:0001399 (Liver failure)
Miscellaneous - Allelic to hereditary multiple leiomyoma of skin (see 150800) and hereditary leiomyomatosis and renal cell cancer (150800)
Metabolic acidosis
Polycythemia, neonatal
FIG4 609390 POLYMICROGYRIA, BILATERAL TEMPOROOCCIPITAL; BTOP #612691   2 Inheritance - HP:0000007 (Autosomal recessive)
Neurologic Central Nervous System Seizures
Complex focal seizures
Visual HP:0000738 (Hallucinations)
Secondary generalization
Automatisms
HP:0002133 (Status epilepticus)
HP:0002119 (ventriculomegaly)
HP:0002126 (Polymicrogyria), temporo-occipital
Behavioral Psychiatric Manifestations Psychiatric abnormalities
HP:0000718 (Aggressive behavior)
Delirium
Variable age at onset, first to second decades
HP:0003828 (Variable severity)
 
FKRP 606596 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 5; MDDGA5 #613153 20301468 4 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Mouth HP:0000158 (Tongue hypertrophy)
Cardiovascular Heart HP:0001644 (dilated cardiomyopathy)
HP:0005162 (Left ventricular impairment)
Respiratory Lung Restrictive HP:0002093 (Respiratory insufficiency)
Decreased forced vital capacity
Nocturnal HP:0002791 (hypoventilation)
Skeletal Spine HP:0002650 (Scoliosis)
Spinal fusion
HP:0003307 (Hyperlordosis)
HP:0002808 (Kyphosis)
Feet Achilles tendon HP:0004576 (large joint contractures)
Muscle, Soft Tissue - HP:0003701 (proximal muscle weakness) HP:0003324 (Muscle weakness)
HP:0002515 (Waddling gait)
HP:0040083 (Toe-walking)
HP:0002355 (Difficulty walking)
Difficulty climbing stairs
HP:0002359 (Frequent falls)
Shoulder girdle HP:0003324 (Muscle weakness)
Hip girdle HP:0003324 (Muscle weakness)
HP:0003394 (Muscle cramps)
HP:0003326 (Myalgia)
HP:0008981 (Calf hypertrophy)
Thigh hypertrophy
HP:0000158 (Tongue hypertrophy)
Muscle MRI shows fatty infiltration
Muscle biopsy shows dystrophic changes
Mildly decreased laminin alpha-2 expression (LAMA2, 156225)
Variably decreased alpha-dystroglycan expression (DAG, 128239)
Laboratory Abnormalities - HP:0003236 (Increased serum creatine kinase)
HP:0002913 (Myoglobinuria), particularly after physical exertion (25% of patients)
Miscellaneous - Variable age of onset (range 1-40 years)
HP:0003828 (Variable severity)
Some patients become wheelchair-bound
Most common mutation is LEU276ILE (606596.0004)
Increased serum creatine kinase
FKTN 607440 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 4; MDDGA4 #253800   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes HP:0000648 (optic atrophy)
HP:0000541 (Retinal detachment)
HP:0000496 (Oculomotor abnormalities)
HP:0000486 (Strabismus)
HP:0000545 (Myopia)
HP:0000540 (Hypermetropia)
HP:0000518 (Cataracts)
HP:0000568 (Microphthalmia)
HP:0007973 (Retinal dysplasia)
Cardiovascular Heart HP:0001685 (Myocardial fibrosis)
HP:0001644 (dilated cardiomyopathy) (onset in second decade)
HP:0001627 (congenital heart defects)
HP:0001631 (Atrial septal defect)
Double subaortic ventricular defect
Hypoplastic left ventricular outlet
HP:0001642 (Pulmonary stenosis)
HP:0001669 (Transposition of the great arteries)
Respiratory - HP:0002093 (Respiratory insufficiency)
Skeletal - HP:0004576 (large joint contractures), progressive
Spine HP:0003306 (Spinal rigidity)
HP:0002650 (Scoliosis)
Muscle, Soft Tissue - HP:0003560 (Muscular dystrophy)
HP:0008947 (Hypotonia, early)
HP:0003202 (Muscle atrophy)
HP:0008981 (Calf hypertrophy)
Muscle biopsy shows decreased glycosylation of alpha-dystroglycan (DAG1, 128239)
Neurologic Central Nervous System HP:0001249 (Intellectual disability)
HP:0001270 (Delayed motor development)
HP:0002126 (Polymicrogyria)
Leptomeningeal thickening
Focal interhemispheric fusion
Low density white matter on CT scan
Cobblestone HP:0001339 (Lissencephaly)
HP:0001302 (pachygyria)
HP:0002126 (Polymicrogyria)
HP:0001339 (Agyria)
HP:0001274 (agenesis of corpus callosum)
HP:0002084 (Encephalocele) (rare)
HP:0000238 (Hydrocephalus)
HP:0002350 (Cerebellar cysts)
White matter changes
Seizures
HP:0002267 (Hyperekplexia) (rare)
HP:0007348 (Pyramidal tract hypoplasia)
HP:0002365 (Brainstem hypoplasia)
HP:0001321 (Cerebellar hypoplasia)
HP:0001360 (holoprosencephaly)
Peripheral Nervous System Hypo- or HP:0001284 (Areflexia)
Laboratory Abnormalities - HP:0003236 (Increased serum creatine kinase)
Miscellaneous - HP:0003593 (Onset in infancy)
Incidence of 1 per 10,000 births in Japan
Increased serum creatine kinase
FLNA 300017 HETEROTOPIA, PERIVENTRICULAR, X-LINKED DOMINANT #300049   1 Inheritance - HP:0001423 (X-linked dominant)
Cardiovascular Heart HP:0001647 (Bicuspid aortic valve)
Vascular HP:0001643 (Patent ductus arteriosus)
Dilation of the sinuses of Valsalva
Dilation of the thoracic aorta
Neurologic Central Nervous System Seizures, refractory to treatment
Imaging shows noncalcified subependymal periventricular heterotopic nodules of gray matter
HP:0001249 (Intellectual disability), mild (in some patients)
HP:0001297 (stroke)s due to HP:0003256 (Coagulopathy)
HP:0002269 (Neuronal migration disorder)
Hematology - HP:0003256 (Coagulopathy)
Miscellaneous - Prenatal or perinatal lethality in hemizygous males
Often confused with tuberous sclerosis (191000)
Otopalatodigital syndrome type I (OPD1, 311300) is an allelic disorder
Otopalatodigital syndrome type II (OPD2, 304120) is an allelic disorder
FrontoHP:0100255 (Metaphyseal dysplasia)(FMD, 305620) is an allelic disorder
Melnick-Needles syndrome (MNS, 309350) is an allelic disorder
 
FLVCR2 610865 PROLIFERATIVE VASCULOPATHY AND HYDRANENCEPHALY-HYDROCEPHALY SYNDROME; PVHH #225790 25677735 2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001511 (Intrauterine growth retardation)
Head and Neck Face HP:0000347 (Micrognathia)
Eyes Glomeruloid vascular proliferation in the retina
Skeletal - Joint HP:0004576 (large joint contractures)
HP:0001558 (Decreased fetal movement) deformation sequence
Limb deformities
Muscle, Soft Tissue - HP:0003202 (Muscle atrophy), neurogenic
Neurologic Central Nervous System HP:0000238 (Hydrocephalus)
HP:0002324 (Hydranencephaly)
HP:0000238 (Hydrocephalus), severe
HP:0002119 (ventriculomegaly)
Glomeruloid vascular proliferation in brain and spinal cord
Endothelial intracytoplasmic globular inclusions
Cortical thinning
HP:0001274 (agenesis of corpus callosum)
HP:0001321 (Cerebellar hypoplasia)
HP:0002365 (Hypoplasia of the brainstem)
HP:0001305 (Dandy-Walker malformation)
Ischemic necrotic lesions
Calcifications in HP:0002135; HP:0007352; white matter, basal ganglia, brainstem, cerebellum, and spinal cord
Prenatal Manifestations - Prenatal diagnosis by ultrasound
Amniotic Fluid HP:0001561 (Polyhydramnios)
Delivery HP:0001622 (Premature delivery)
Miscellaneous - Stillborn or neonatal death
Diagnosis occurs between 23 and 33 weeks' gestation
Variable clinical presentation
 
FMN2 606373 MENTAL RETARDATION, AUTOSOMAL RECESSIVE 47; MRT47 616193   2 Inheritance - HP:0000007 (Autosomal recessive)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early) (in some patients)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
HP:0000750 (language delay)
Complex partial seizures (in some patients)
Miscellaneous - HP:0003593 (Onset in infancy)
 
FMR1 309550 FRAGILE X MENTAL RETARDATION SYNDROME #300624   2 Inheritance - HP:0001423 (X-linked dominant)
Head and Neck Head HP:0000256 (Macrocephaly)
Face HP:0000280 (Coarse facies)
HP:0002003 (Large forehead)
HP:0000276 (Long face)
HP:0000303 (Prominent jaw)
Ears HP:0000400 (macrotia)
Cardiovascular Heart HP:0001634 (Mitral valve prolapse)
Chest Ribs, Sternum, Clavicles and Scapulae HP:0000767 (HP:0000766 (Pectus deformities) excavatum)
Genitourinary External Genitalia (Male) HP:0000053 (Macroorchidism), postpubertal
Congenital HP:0000053 (Macroorchidism) (in some patients)
Skeletal Spine HP:0002650 (Scoliosis)
Limbs HP:0001388 (Joint laxity)
Feet HP:0001763 (pes planus)
Neurologic Central Nervous System HP:0001249 (Intellectual disability) (moderate to severe in males)
Seizures
Abnormal head movements
Periventricular HP:0002282 (heterotopia)
Behavioral Psychiatric Manifestations HP:0000752 (hyperactivity)
HP:0000817 (Poor eye contact)
HP:0000729 (autistic behaviour)
Laboratory Abnormalities - Folate-dependent fragile site at Xq28
Miscellaneous - HP:0003829 (Incomplete penetrance)
50% of females have learning disability or mild HP:0001249 (Intellectual disability)
Prevalence approximately 1 in 4,000 males
Most cases (98%) caused by expanded trinucleotide repeat (CGG)n in the FMR1 gene (309550.0004)
Repeat is unstable if > 52 repeats
Symptomatic if > 200 repeats
Some boys with premutations (55 to 200 repeats) may show milder features, including HP:0000729 (autistic behaviour)
 
FOLR1 136430 NEURODEGENERATION DUE TO CEREBRAL FOLATE TRANSPORT DEFICIENCY #613068    2 Inheritance - HP:0000007 (Autosomal recessive)
Neurologic Central Nervous System HP:0002376 (Psychomotor regression), severe
HP:0002180 (Neurodegeneration)
Seizures
Motor dysfunction
HP:0001249 (Intellectual disability) (if untreated)
Disturbed myelination affecting the periventricular and subcortical white matter
Brain MRS shows reduced choline and inositol peaks in the parieto-occipital white matter
Laboratory Abnormalities - Decreased CSF methyltetrahydrofolate (MTHF)
Miscellaneous - Onset beyond the second year of life
Treatment with oral folic acid can ameliorate, resolve, or prevent clinical symptoms and myelination defects
Decreased methyltetrahydrofolate (MTHF) )
FOXG1 164874 RETT SYNDROME, CONGENITAL VARIANT #613454   2 Inheritance - HP:0003745 (Isolated cases)
Growth Other HP:0008897 (Postnatal growth retardation)
Head and Neck Head HP:0000252 (microcephaly), postnatal, progressive
Eyes HP:0000817 (Poor eye contact)
Mouth HP:0003763 (bruxism)
HP:0100703 (Tongue thrusting)
HP:0002307 (drooling)
Respiratory - Abnormal breathing patterns
Abdomen Gastrointestinal HP:0002020 (Gastroesophageal reflux)
HP:0002019 (Constipation)
Skeletal Spine HP:0002650 (Scoliosis)
HP:0002808 (Kyphosis)
Limbs HP:0002857 (Genua valga)
Feet HP:0001763 (pes planus)
HP:0001762 ( Pes equinovarus)
Neurologic Central Nervous System HP:0001249 (Intellectual disability), severe
Neonatal HP:0008947 (Hypotonia, early)
Neonatal irresponsiveness
NeonatalHP:0000737 (Irritability)
HP:0001270 (Delayed motor development)
HP:0002376 (Psychomotor regression) before age 6 months
HP:0002186 (Apraxia)
Seizures
Jerky limb movements
HP:0000733 (Stereotypic behavior)
HP:0001257 (Spasticity)
HP:0100660 (dyskinesia)
HP:0002072 (Chorea)
HP:0002305 (Athetosis)
HP:0007325 (generalized dystonia)
HP:0001344 (absent speech) development
HP:0000735 (Impaired social interactions)
Abnormal sleep patterns
EEG abnormalities
EEG shows with a multifocal pattern with spikes and sharp waves
HP:0002079 (Hypoplasia of corpus callosum)
HP:0012448 (Delayed myelination)
HP:0009879 (Simplified gyral pattern)
Reduced white matter volume
HP:0001302 (pachygyria)
Miscellaneous - Normal birth
Onset in the first months of life
All reported cases have occurred de novo
Most patients do not learn to sit or walk
Seizure onset after 3 months
 
FOXRED1 613622 LEIGH SYNDROME; LS 256000   2 Inheritance - HP:0000007 (Autosomal recessive)
Mitochondrial
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Eyes HP:0000544 (Ophthalmoplegia)
HP:0000648 (optic atrophy)
HP:0000639 (Nystagmus)
HP:0000486 (Strabismus)
HP:0000508 (Ptosis)
HP:0000580 (Pigmentary retinopathy)
Respiratory - HP:0002793 (Abnormal respiratory patterns)
HP:0002878 (Respiratory failure)
Skin, Nails, Hair Hair HP:0000998 (hypertrichosis)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System HP:0001263 (global developmental delay)
HP:0008947 (Hypotonia, early)
HP:0001251 (ataxia)
HP:0007325 (generalized dystonia)
HP:0001260 (Dysarthria)
HP:0001257 (Spasticity)
HP:0001347 (Hyperreflexia)
Seizures
Brainstem abnormalities
HP:0001249 (Intellectual disability)
Lesions in basal ganglia, brainstem, cerebellum, thalamus, spinal cord characterized by HP:0007305 (CNS demyelination), necrosis, HP:0002171 (Gliosis), spongiosis, and capillary proliferation
Behavioral Psychiatric Manifestations HP:0000712 (Emotional lability)
Metabolic Features - HP:0003128 (Lactic acidosis)
Laboratory Abnormalities - HP:0002151 (Increased serum lactate)
HP:0002490 (Increased CSF lactate)
Miscellaneous - Onset usually in infancy or early childhood
HP:0003676 (Progressive disorder), usually with rapid, relentless course
Clinical heterogeneity
Genetic heterogeneity (may be caused by mutation in nuclear-encoded or mitochondrial-encoded genes)
Subset of patients have cytochrome c oxidase deficiency (see 220110)
See also X-linked Leigh syndrome (312170)
See also French-Canadian type of Leigh syndrome (220111)
Lactic acidosis
Increased lactate (P, C)
FRRS1L 604574 EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 37; EIEE37 616981     Inheritance -
HP:0000007 (Autosomal recessive)
Head and Neck Eyes
HP:0000639 (Nystagmus) (in some patients)
Muscle, Soft Tissue -
HP:0008947 (Hypotonia)
Neurologic Central Nervous System
HP:0200134 (Epileptic encephalopathy)
HP:0001263 (Global developmental delay)
HP:0002376 (Psychomotor regression)
HP:0001249 (Intellectual disability)
HP:0001344 (absent speech)
Seizures, intractable
HP:0002487 (Hyperkinesis)
Impaired gait
HP:0002505 (Progressive inability to walk)
HP:0001266 (Choreoathetosis)
HP:0001257 (Spasticity)
HP:0002063 (Rigidity)
HP:0001336 (myoclonus)
Impaired volitional movement
HP:0002283 (Generalized brain atrophy)
HP:0001272 (Cerebellar atrophy)
Flattening of the caudate heads
 
FTL 134790 L-FERRITIN DEFICIENCY; LFTD #615604   2 Inheritance - HP:0000006 (Autosomal dominant)
HP:0000007 (Autosomal recessive)
Skin, Nails, Hair Hair HP:0001596 (alopecia), progressive (homozygous patient)
Neurologic Central Nervous System Idiopathic generalized epilepsy in childhood (homozygous patient)
NeuroHP:0100543 (Cognitive impairment), mild (homozygous patient)
Hematology - Normal hematologic parameters (both patients)
Laboratory Abnormalities - Undetectable serum L-transferrin (homozygous patient)
Decreased serum L-transferrin (heterozygous patient)
Decreased L-transferrin (P)
Increased citric acid cycle intermediates (U)
Increased fumaric acid (U)
Increased malic acid (U)
Increased succinic acid (U)
FTO 610966 GROWTH RETARDATION, DEVELOPMENTAL DELAY, COARSE FACIES, AND EARLY DEATH; GDFD 612938   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001511 (Intrauterine growth retardation)
HP:0001508 (Failure to thrive), severe
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0000280 (Coarse facies)
HP:0000278 (Retrognathia)
Prominent alveolar ridge
Ears HP:0000407 (Sensorineural hearing loss)
Eyes Optic disc abnormalities
Nose HP:0000463 (Anteverted nostrils)
Mouth HP:0000233 (Thin vermilion border)
HP:0000175 (Cleft palate)
HP:0000193 (Bifid uvula)
HP:0010808 (Protruding tongue)
Neck HP:0000470 (Short neck)
Cardiovascular Heart HP:0001629 (Ventricular septal defect)
HP:0006695 (Atrioventricular defect)
HP:0001639 (hypertrophic cardiomyopathy)
Vascular HP:0001643 (Patent ductus arteriosus)
Genitourinary External Genitalia (Male) HP:0000062 (Ambiguous genitalia)
External Genitalia (Female) HP:0000062 (Ambiguous genitalia)
Hypertrophy of the labia
Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
Skeletal Skull HP:0002678 (Skull asymmetry)
Hands HP:0009803 (short fingers)
Drumstick fingers
Skin, Nails, Hair Skin HP:0000965 (Cutis marmorata)
Nails HP:0001800 (Hypoplastic toenails)
Muscle, Soft Tissue - HP:0001537 (Umbilical hernia)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay), severe
HP:0001276 (Hypertonicity)
HP:0000238 (Hydrocephalus)
HP:0001339 (Lissencephaly)
Seizures
HP:0001305 (Dandy-Walker malformation)
Miscellaneous - Death by age 3 years
 
FTSJ1 300499 MENTAL RETARDATION, X-LINKED 9; MRX9 309549   2 0  
FUCA1 612280 FUCOSIDOSIS #230000   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Other HP:0008897 (Postnatal growth retardation)
Head and Neck Head Normal head circumference
Face HP:0000280 (Coarse facies)
HP:0011220 (Prominent forehead)
EarsHP:0000410 (Hearing loss, mixed)
Eyes HP:0000316 (Hypertelorism)
HP:0011229 (Broad eyebrows)
Tortuosity of conjunctival vessels
Nose HP:0000445 (Broad nose)
Mouth
HP:0012471 (Thick lips)
Cardiovascular Heart HP:0001640 (Cardiomegaly)
Respiratory - HP:0002205 (Recurrent respiratory infections)
Chest External Features Broad chest
Ribs, Sternum, Clavicles and Scapulae Wide clavicles
Spatulated ribs
Abdomen External Features HP:0100790 (Hernia)
Liver HP:0002240 (Hepatomegaly)
Spleen HP:0001744 (Splenomegaly)
Skeletal - HP:0000943 (dysostosis multiplex)
Skull Progressive thickening of diploic spaces
HP:0005453 (Absent/hypoplastic paranasal sinuses)
Spine Lumbar hyperHP:0003307 (Hyperlordosis)
Short odontoid
Cervical HP:0000926 (Platyspondyly)
Anterior beaking of thoracic and lumbar vertebrae
HP:0002650 (Scoliosis)
Small fifth lumbar vertebrae
Absent/hypoplastic coccyx
Pelvis Widened, scalloped acetabular roof
HP:0002673 (Coxa valga)
Limbs Joint contracture
Skin, Nails, Hair Skin HP:0001014 (Angiokeratoma)
Thin, HP:0000958 (Dry skin)
HP:0000970 (Anhidrosis)
Neurologic Central Nervous System HP:0001249 (Intellectual disability)
HP:0008947 (Hypotonia, early) changing to HP:0001276 (Muscle hypertonia)
Spastic HP:0002445 (quadriplegia)
Seizures
HP:0002283 (global brain atrophy)
Peripheral Nervous System HP:0009830 (Peripheral neuropathy)
Laboratory Abnormalities - Elevated sweat chloride
HP:0001922 (Vacuolated lymphocytes)
Increased urine oligosaccharides
Alpha-L-fucosidase deficiency
Miscellaneous - Majority of patients from Italy and Southwestern United States
Two types - severe infantile form (type I) and milder form (type II)
Increased sweat chloride
Vacuolated lymphocytes
Increased oligosaccharides (U)
FXYD2 601814 HYPOMAGNESEMIA 2, RENAL; HOMG2 #154020   2 Inheritance - HP:0000006 (Autosomal dominant)
Genitourinary Kidneys HP:0005567 (Renal magnesium wasting)
Neurologic Central Nervous System Seizures
Laboratory Abnormalities - HP:0002917 (Hypomagnesemia)
Decreased renal calcium excretion
Normal parathyroid hormone
Hypomagnesemia
GABBR2 607340 Epileptic encephalopathy   25262651 2 0  
GABRB3 137192 Early infantile epileptic encephalopathy   26645412 2 0  
GABRG2 137164 FEBRILE SEIZURES, FAMILIAL, 8, INCLUDED; FEB8, INCLUDED 611277   2 Inheritance - HP:0000006 (Autosomal dominant)
Neurologic Central Nervous System HP:0002373 (febrile seizures)
Generalized HP:0002069 (Tonic-clonic seizures)
AHP:0002373 (febrile seizures)
HP:0002121 (Absence seizures)
Partial seizures
HP:0010819 (atonic seizures)
Miscellaneous - HP:0003828 (Variable severity)
Onset of HP:0002373 (febrile seizures) typically between 6 months and 6 years of age
Simple HP:0002373 (febrile seizures) usually remit by age 6 years
Some patients have a more severe phenotype and have febrile and aHP:0002373 (febrile seizures) after childhood (GEFS+)
 
GAL 137035 EPILEPSY, FAMILIAL TEMPORAL LOBE, 8; ETL8 616461   2 Inheritance - HP:0000006 (Autosomal dominant)
Neurologic Central Nervous System Temporal lobe epilepsy
Complex partial seizures
HP:0011157 (Auras)
Secondary generalization
Miscellaneous - Onset in teenage years
Favorable response to antiepileptic medication
 
GALC 606890 KRABBE DISEASE #245200   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Ears Deafness
Abnormal brainstem auditory evoked potentials (BAEP)
Eyes HP:0000618 (Blindness)
HP:0000648 (optic atrophy)
Abnormal flash visual evoked potentials (VEP)
HP:0000639 (Nystagmus)
Abdomen Gastrointestinal HP:0002013 (Vomiting)
Neurologic Central Nervous System HyperHP:0000737 (Irritability)
Hypersensitive to stimuli
HP:0001268 (cognitive decline)
HP:0002180 (Neurodegeneration)
HP:0002376 (Psychomotor regression)
Progressive HP:0001257 (Spasticity)
Hyperactive deep tendon reflexes in early stage
Decerebrate posturing
HP:0001276 (Muscle hypertonia) in early stage
HP:0008947 (Hypotonia, early) in later stages
Seizures
HP:0000238 (Hydrocephalus)
Diffuse HP:0002283 (global brain atrophy) on CT and MRI
HP:0002333 (Motor deterioration)
Abnormal EEG
'Globoid multinucleated cells' in brain tissue
Loss of myelin and oligodendroglia
HP:0007305 (CNS demyelination)
Peripheral Nervous System Sensorimotor HP:0009830 (Peripheral neuropathy)
Diffuse HP:0007108 (demyelinating peripheral neuropathy)
Decreased nerve conduction velocities
Laboratory Abnormalities - Elevated cerebrospinal fluid (CSF) protein
Galactocerebroside beta-galactosidase deficiency in serum, leukocytes, and fibroblasts
Miscellaneous - HP:0001954 (Episodic fever)
Four clinical forms of Krabbe disease
Infantile form has onset within first 6 months of life
Infantile form accounts for 90% of cases
Infantile form usually leads to death by age 2 years
Late infantile form has onset between 19 months and 4 years
Juvenile form has onset between 4 and 19 years
Adult form onset has after 20 years
Incidence of 1 in 100,000
Increased protein )
GAMT 601240 CEREBRAL CREATINE DEFICIENCY SYNDROME 2; CCDS2 #612736    1 Inheritance - HP:0000007 (Autosomal recessive)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early) in infancy
Neurologic Central Nervous System Progressive HP:0002071 (Extrapyramidal signs)
HP:0012758 (neurodevelopmental delay) or regression
HP:0001249 (Intellectual disability)
HP:0001251 (ataxia)
Seizures, intractable
HP:0000750; Absent or limited speech development
HP:0001276 (Hypertonicity) in lower limbs
HP:0001347 (Increased deep tendon reflexes)
HP:0001336 (myoclonus)
Laboratory Abnormalities - Extremely low creatine excretion
Low CSF creatine
Low CSF creatinine
Deficiency of creatine phosphate in brain
Accumulation of guanidinoacetate in brain
Guanidinoacetate methyltransferase (GAMT) deficiency
Miscellaneous - Clinical and biochemical symptoms improved with oral administration of creatine monohydrate
Low creatine (C)
Low creatinine )
GATA6 601656 HEART DEFECTS, CONGENITAL, AND OTHER CONGENITAL ANOMALIES; HDCA 600001   2 Inheritance - HP:0000006 (Autosomal dominant)
Growth Other HP:0001511 (Intrauterine growth retardation)
HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000252 (microcephaly) (in some patients)
Cardiovascular Heart HP:0001655 (Patent foramen ovale)
HP:0001643 (Patent ductus arteriosus)
HP:0001631 (Atrial septal defect)
HP:0001629 (Ventricular septal defect), perimembranous
HP:0001629 (Ventricular septal defect)s, muscular
Right ventricular hypoplasia
Double-outlet left ventricle
HP:0001636 (Tetralogy of Fallot)
Tricuspid valve hypoplasia
Valvular HP:0001642 (Pulmonary stenosis)
Absence of the pericardium, congenital (rare)
Vascular HP:0001660 (Truncus arteriosus)
HP:0001642 (Pulmonary stenosis)
Hypoplastic pulmonary artery
HP:0004415 (Pulmonary artery stenosis), bilateral branch
Interrupted aortic arch
Chest Ribs, Sternum, Clavicles and Scapulae Bilateral HP:0000891 (cervical rib)s (rare)
Absent right 12th rib (rare)
Diaphragm HP:0000776 (Diaphragmatic hernia) (in some patients)
Abdomen External Features HP:0001537 (Umbilical hernia) (rare)
Liver Hepatic inflammation
Pancreas Pancreatic agenesis or severe hypoplasia
Biliary Tract Gall bladder agenesis
HP:0005912 (biliary atresia) (in some patients)
Gastrointestinal Colon perforation (rare)
Intestinal HP:0002566 (Malrotation) (rare)
Microcolon (rare)
Genitourinary External Genitalia (Male) HP:0000023 (Inguinal hernia) (in some patients)
Ureters HP:0000073 (duplicated ureters) (rare)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
Seizures (in some patients)
Pituitary agenesis (rare)
Endocrine Features - HP:0003074 (Hyperglycemia)
Exocrine pancreatic deficiency
Transient HP:0000821 (Hypothyroidism) (in some patients)
Prenatal Manifestations Placenta and Umbilical Cord Single umbilical artery (rare)
Miscellaneous - Patients frequently have additional malformations or abnormalities, especially in the hepatobiliary and gastrointestinal systems
 
GATM 602360 CEREBRAL CREATINE DEFICIENCY SYNDROME 3; CCDS3 612718     Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Muscle, Soft Tissue - HP:0003324 (Muscle weakness), predominantly proximal (in some patients)
Gowers sign (in some patients)
Muscle biopsy shows fiber type variation (in some patients)
Neurologic Central Nervous System HP:0001263 (Global developmental delay)
HP:0001249 (intellectual disability), mild to moderate
HP:0000750 (language delay)
Brain MRS shows decreased creatine content
Behavioral Psychiatric Manifestations Autistic behavior
Laboratory Abnormalities - Decreased plasma and urinary guanidinoacetate (GAA)
Organic aciduria
Miscellaneous - Onset in infancy
Favorable response to oral creatine treatment
Decreased guanidinoacetate (GAA) (P, U)
GBA 606463 GAUCHER DISEASE, TYPE III #231000    2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature)
Weight Decreased weight
Head and Neck Eyes HP:0000496 (Oculomotor abnormalities)
Abnormal saccades
HP:0000605 (Supranuclear gaze palsy), horizontal (type IIIB)
Vertical ocular movements are usually preserved
HP:0000486 (Strabismus)
Abdomen Liver HP:0002240 (Hepatomegaly)
Spleen HP:0001744 (Splenomegaly)
Neurologic Central Nervous System Subacute HP:0002344 (Neurologic deterioration)
Seizures
HP:0001270 (Delayed motor development)
HP:0001268 (cognitive decline)
Speech abnormalities
HP:0001251 (ataxia)
HP:0002313 (spastic paraparesis)
HP:0001336 (myoclonus) (subtype 3A)
HP:0002123 (Myoclonic seizures) (subtype 3A)
HP:0000726 (Dementia) (subtype 3A)
Behavioral Psychiatric Manifestations HP:0000716 (Depression)
Hematology - Gaucher cells in bone marrow
HP:0001876 (Pancytopenia)
HP:0001873 (thrombocytopenia)
Laboratory Abnormalities - Decreased beta-glucocerebrosidase protein and activity
Miscellaneous - HP:0003812 (Variable phenotype)
Onset usually in childhood (range infancy to late childhood)
Adult onset has been reported
Subtype 3A comprises HP:0001336 (myoclonus) and HP:0000726 (Dementia)
Subtype 3B comprises horizontal HP:0000605 (Supranuclear gaze palsy) and aggressive systemic disease
Subtype 3C (231005) comprises cardiovascular calcifications
Gaucher cells in bone marrow
GCDH 608801 GLUTARIC ACIDEMIA I #231670   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000256 (Macrocephaly)
Abdomen Liver HP:0002240 (Hepatomegaly)
Neurologic Central Nervous System HP:0007325 (generalized dystonia)
HP:0008947 (Hypotonia, early)
HP:0002063 (Rigidity)
HP:0001266 (Choreoathetosis)
HP:0002179 (Opisthotonus)
Seizures (less common)
Infantile HP:0004319 (nonprogressive encephalopathy)
HP:0001264 (Spastic diplegia)
HP:0006892 (Frontotemporal atrophy)
HP:0002119 (ventriculomegaly)
Widening of cortical sulci
HP:0012448 (Delayed myelination)
Symmetrical progressive HP:0007305 (CNS demyelination)
Hypodensity of lenticular nuclei
Hypodensity of caudate
Striatal necrosis
Laboratory Abnormalities - Glutarica ciduria
Glutaryl-CoA dehydrogenase deficiency
HP:0001942 (metabolic acidosis)
HP:0001946 (ketosis)
HP:0002919 (Ketonuria)
HP:0001943 (Hypoglycemia)
Miscellaneous - Variable clinical presentation ranging from acute onset to normal adult
Prevalent in Old Order Amish of Lancaster County, Pennsylvania and Saulteaux/Ojibway Indians of Canada
Onset of illness often associated with acute infection
Worldwide frequency of 1 in 100,000 infants
Glutaricaciduria
GCH1 600225 HYPERPHENYLALANINEMIA, BH4-DEFICIENT, B; HPABH4B #233910   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0011968 (feeding difficulties)in infancy
Head and Neck Eyes HP:0000496 (oculomotor abnormalities)
Mouth HP:0002307 (drooling)
Abdomen Gastrointestinal HP:0002015 (Swallowing difficulties)
Neurologic Central Nervous System HP:0001263 (global developmental delay)
HP:0001263 (global developmental delay)
HP:0001249 (Intellectual disability)
HP:0008947 (Hypotonia, early), truncal
HP:0001276 (Muscle hypertonia) of the extremities
HP:0002311 (Incoordination)
HP:0002322 (Resting tremor)
HP:0007325 (generalized dystonia)
HP:0002063 (Rigidity)
HP:0002487 (Hyperkinesis)
Seizures
HP:0001266 (Choreoathetosis)
HP:0001254 (Lethargy)
Behavioral Psychiatric ManifestationsHP:0000737 (Irritability)
Metabolic Features - HP:0001954 (Episodic fever)
Laboratory Abnormalities - Hyperphenylalaninemia
Decreased homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) in CSF
Decreased neopterin and biopterin in urine
Decreased neopterin and biopterin in CSF
Decreased or absent GCH1 activity
Miscellaneous - HP:0003593 (Onset in infancy)
HP:0003828 (Variable severity)
Defect in tetrahydrobiopterin (BH4) synthesis
Progressive HP:0002344 (Neurologic deterioration) if untreated
Normal neonatal blood phenylalanine has been reported in rare patients
Diurnal fluctuation of neurologic symptoms
Treatment with BH4 is effective
Neurotransmitter treatment with L-dopa and serotonin or precursors is effective
Early treatment can reduce neurologic symptoms
HP:0000006 (Autosomal dominant) dopa-responsive HP:0007325 (generalized dystonia) (DYT5, 128230) is an allelic disorder with overlapping features
Hyperphenylalaninemia
Decreased homovanillic acid and 5-hydroxyindoleacetic acid (C)
Decreased neopterin and biopterin (U, C)
GCK 138079 DIABETES MELLITUS, PERMANENT NEONATAL; PNDM #606176    2 Inheritance - HP:0000006 (Autosomal dominant)
Growth Weight HP:0001518 (Small for gestational age)
Other HP:0001511 (Intrauterine growth retardation)
Postnatal growth catch-up occurs in treated patients without neurologic abnormalities
Head and Neck Head HP:0005487 (Metopic ridging)
Face HP:0000343 (Long philtrum)
Ears HP:0009894 (Thick ears)
Eyes HP:0000508 (Ptosis)
Nose Small, HP:0003196 (Short nose)
HP:0000463 (Anteverted nostrils)
Mouth HP:0002714 (Downturned mouth)
Abdomen Pancreas HP:0006279 (Beta-cell dysfunction)
Skeletal - Limb HP:0004576 (large joint contractures)
Hands HP:0004209 (Fifth finger clinodactyly)
Muscle, Soft Tissue - HP:0003324 (Muscle weakness)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
HP:0001270 (Delayed motor development)
Axial HP:0008947 (Hypotonia, early)
Diffuse HP:0008947 (Hypotonia, early)
Seizures
HP:0002521 (hypsarrhythmia)
EEG shows epileptiform activity
Peripheral Nervous System Diabetic HP:0009830 (Peripheral neuropathy) in long-standing cases
Endocrine Features - HP:0000819 (Diabetes mellitus)
Immunology - Absence of pancreatic autoantibodies
Laboratory Abnormalities - HP:0003074 (Hyperglycemia)
HP:0001993 (ketoacidosis)
Miscellaneous - Diagnosis within the first 3 months of life
Some patients do not show neurologic abnormalities or HP:0001999 (Dysmorphic features)
Some patients show a favorable response to sulfonylurea treatment
 
GCM2 603716 HYPOPARATHYROIDISM, FAMILIAL ISOLATED; FIH 146200   3 Eyes HP:0000518 (Cataracts)
Radiology HP:0002514 (Cerebral calcification) on CT scan
Neuro Seizures
Chronic HP:0001281 (Tetany)
Inheritance HP:0000006 (Autosomal dominant)
Endocrine HP:0000829 (Hypoparathyroidism)
Lab No circulating antibodies to parathyroid hormone
Undetectable or subnormal plasma immunoreactive PTH
HP:0002901 (hypocalcemia)
HP:0002905 (Hyperphosphatemia)
 
GCSH 238330 GLYCINE ENCEPHALOPATHY; GCE 605899   1 Inheritance - HP:0000007 (Autosomal recessive)
Neurologic Central Nervous System HP:0001274 (agenesis of corpus callosum) (variable)
HP:0001254 (Lethargy)
Seizures
HP:0100247 (Hiccups)
HP:0008947 (Hypotonia, early)
HP:0001265 (Hyporeflexia) to HP:0001347 (Hyperreflexia)
HP:0001336 (myoclonus)
HP:0001249 (Intellectual disability)
HP:0010851 (Burst suppression pattern) on neonatal EEG
Expressive speech deficit
Behavioral Psychiatric Manifestations HP:0000752 (Hyperactivity)
HP:0100710 (Impulsivity)
HP:0000718 (aggressive behavior)
HP:0000737 (Irritability)
HP:0000711 (Restlessness)
Laboratory Abnormalities - Hyperglycinemia
Hyperglycinuria
Hepatic glycine cleavage defect
Elevated CSF glycine
Elevated CSF/plasma glycine ratio
Miscellaneous - HP:0001522 (Death in infancy) common for patients with the classic neonatal form
Patients with atypical form have milder disease, with onset in the first months of life and increased survival
Hyperglycinemia
Hyperglycinuria
Increased CSF glycine
Increased CSF/plasma glycine ratio
GFAP 137780 ALEXANDER DISEASE; ALXDRD #203450   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Head Progressive HP:0000256 (Macrocephaly)
Neurologic Central Nervous SystemHP:0002376 (Psychomotor regression)
HP:0001257 (Spasticity)
Seizures
Diffuse HP:0007305 (CNS demyelination) (increased signal intensity in T2-weighted images, especially frontal lobes)
Coarsened pattern of sulci and gyri
Presence of Rosenthal fibers (eosinophilic bodies near astrocyte filaments)
HP:0000238 (Hydrocephalus)
Laboratory Abnormalities - Presence of Rosenthal fibers (cytoplasmic inclusions) in astrocytes
Presence of glial fibrillary acidic proteins (GFAP) in astrocytes
HP:0002922 (Elevated CSF protein)
Miscellaneous - Average age of onset 6 months (range birth - 2 years)
Death by age 5 (infantile form)
Three variants distinguished by age of onset - infantile ( onset before age 2), juvenile (onset in childhood), and adult
Juvenile patients have slower clinical course with preserved intellect, bulbar signs, HP:0001251 (ataxia), and HP:0001257 (Spasticity)
Adult patients have heterogeneous symptoms including some with relapsing-remitting symptoms similar to multiple sclerosis
 
GFM1 606639 COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 1; COXPD1 #609060   1 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001511 (Intrauterine growth retardation)
Head and Neck Head HP:0000252 (microcephaly), mild
Eyes HP:0000817 (Poor eye contact)
HP:0000639 (Nystagmus)
Abdomen Liver Fulminant HP:0001399 (Liver failure) (in 2 sibs)
HP:0002605 (Liver necrosis)
HP:0001396 (Cholestasis)
HP:0002240 (Hepatomegaly)
Gastrointestinal HP:0011968 (feeding difficulties)
Neurologic Central Nervous System 'Stiffness'
HP:0002375 (Decreased spontaneous movement)
HP:0001270 (Delayed motor development)
Axial HP:0008947 (Hypotonia, early)
HP:0001257 (Spasticity)
HP:0001347 (Hyperreflexia)
Seizures, refractory
HP:0002079 (Hypoplasia of the corpus callosum)
HP:0012448 (Delayed myelination)
HP:0002283 (global brain atrophy)
Cystic lesions in the basal ganglia
Metabolic Features - HP:0001942 (metabolic acidosis), severe
Laboratory Abnormalities - HP:0002151 (Increased serum lactate)
HP:0002490 (Increased CSF lactate)
Increased serum direct bilirubin
Fibroblasts show decreased activity of mitochondrial respiratory complex I, complex III, complex IV, and complex V
Miscellaneous - HP:0003577 (Onset at birth)
Death within first months or years of life
Increased lactate (P, C)
GJA1 121014 OCULODENTODIGITAL DYSPLASIA; ODDD 164200   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Head HP:0000252 (microcephaly)
Ears HP:0000377 (Dysplastic ears) (in some patients)
HP:0000405 (Conductive hearing loss)
Eyes HP:0000482 (Microcornea)
HP:0000568 (Microphthalmia)
HP:0012745 (Short palpebral fissures)
HP:0000286 (Epicanthus)
HP:0000501 (Glaucoma)
HP:0000518 (Cataracts)
Iris anomalies
Nose Small nares
Thin HP:0000430 (Hypoplastic nasal alae) nasi
Narrow nasal bridge
Thin HP:0000463 (Anteverted nares)
Prominent columella
Mouth HP:0100333 (Unilateral cleft lip)
HP:0000175 (Cleft palate)
HP:0000187 (Broad alveolar ridges)
Teeth HP:0006297 (Enamel hypoplasia)
Selective HP:0009804 (tooth agenesis)
HP:0000691 (Microdontia)
HP:0006480 (Premature loss of teeth)
HP:0000670 (Dental caries)
HP:0000679 (Taurodontism)
Cardiovascular Heart Endocardial cushion defects (uncommon)
HP:0001631 (Atrial septal defect) (uncommon)
HP:0001629 (Ventricular septal defect) (uncommon)
HP:0011675 (Arrhythmia) (uncommon)
Abdomen Gastrointestinal Bowel dysfunction (in some cases)
Genitourinary Bladder HP:0000011 (Neurogenic bladder) (in some patients)
Skeletal Skull Skull HP:0100774 (Hyperostosis)
Spine Vertebral HP:0100774 (Hyperostosis)
Pelvis HP:0002827 (Hip dislocations)
Limbs Broad tubular bones
HP:0002967 (Cubitus valgus)
Hands HP:0006101 (Finger syndactyly) of 4th - 5th fingers
Short middle phalanx of the 5th finger
Fifth finger HP:0100490 (Camptodactyly)
Midphalangeal hypoplasia
HP:0004209 (Fifth finger clinodactyly)
Feet HP:0006101 (syndactyly) of 3rd - 4th toes
Skin, Nails, Hair Skin Diffuse yellow-orange non-epidermolytic HP:0010765; HP:0007556 (hyperkeratosis on palms and soles) (palmoplantar keratoderma)
Nails HP:0001808 (Brittle nails)
Hair Fine, dry hair
Sparse, slow-growing hair
Muscle, Soft Tissue - HP:0001004 (Lymphedema) of lower limbs (in some patients)
Neurologic Central Nervous System HP:0001249 (Intellectual disability) (rare)
Hyperactive deep tendon reflexes
HP:0002385 (Paraparesis)
HP:0002273 (Quadriplegia)
HP:0001251 (ataxia)
HP:0001257 (Spasticity)
HP:0001260 (Dysarthria)
Seizures
HP:0000011 (Neurogenic bladder)
HP:0002135 (Basal ganglia calcification)
Cerebral HP:0002500 (White matter abnormalities)
Miscellaneous - HP:0003812 (Variable phenotype)
Cardiac features are observed in ~3% of cases
Neurologic features have been diagnosed in ~30% of cases
50% of cases represent new mutations associated with advanced paternal age
 
GJC2 608803 LEUKODYSTROPHY, HYPOMYELINATING, 2; HLD2 #608804   5 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0002599 (Head titubation)
Face Facial HP:0003324 (Muscle weakness)
Eyes Rotary HP:0000639 (Nystagmus)
HP:0000648 (optic atrophy)
HP:0000545 (Myopia)
Neurologic Central Nervous System Poor head and trunk control in infancy
HP:0001263 (Delayed psychomotor development)
Motor developmental milestones not achieved
HP:0002540 (inability to walk)
HP:0002322 (Resting tremor), intention
HP:0002599 (Head titubation)
Truncal HP:0008947 (Hypotonia, early)
HP:0001251 (ataxia)
HP:0001257 (Spasticity), progressive
HP:0002313 (spastic paraparesis)
HP:0003487 (Extensor plantar responses)
HP:0007325 (generalized dystonia)
HP:0002063 (Rigidity)
HP:0001266 (Choreoathetosis)
HP:0001260 (Dysarthria)
Seizures
Mental impairment, mild to moderate
HP:0000750 (language delay)
HP:0002283 (global brain atrophy)
HP:0002415 (Leukodystrophy), hypomyelinating
Loss of white matter
MRI shows diffuse white matter hyperintensities on T2-weighted imaging
Peripheral Nervous System HP:0009830 (Peripheral neuropathy), mild (less common)
Decreased motor nerve conduction velocities (NCV)
HP:0007220 (Demyelinating motor neuropathy)
HP:0003390 (Sensory axonal neuropathy)
Miscellaneous - HP:0003593 (Onset in infancy)
Most children become wheelchair-bound
Similar disorder to X-linked Pelizaeus-Merzbacher disease (PMD, 312080)
 
GLA 300644 FABRY DISEASE 301500   4 Inheritance - X-linked
Growth Other HP:0001510 (Growth delay)
HP:0000823 (Delayed puberty)
Head and Neck Eyes HP:0007957; Corneal and lenticular opacities
Whorl-like corneal dystrophy in carrier females
Cardiovascular Heart HP:0001681 (Angina)
Electrocardiographic changes
HP:0001712 (Left ventricular hypertrophy)
HP:0005144 (Ventricular septal hypertrophy)
HP:0000822 (Hypertension)
HP:0001658 (Myocardial infarction)
Valvular disease (mitral)
HP:0001635 (Congestive heart failure)
Respiratory Lung Mild HP:0006536 (obstructive lung disease)
Abdomen Gastrointestinal HP:0002027 (Abdominal pain)
Episodic HP:0002014 (Diarrhea)
HP:0002018 (Nausea)
HP:0002013 (Vomiting)
Tenesmus
Genitourinary Kidneys HP:0000083 (Renal failure)
Isosthenuria
Renal biopsy shows glomerular sclerosis
Vacuolization of glomerular and tubular epithelial cells
Skeletal Hands Limited extension of terminal joints
Skin, Nails, Hair Skin HP:0000966 (Hypohidrosis)
HP:0001014 (Angiokeratoma)
Muscle, Soft Tissue - HP:0003394 (Muscle cramps)
HP:0002380 (Fasciculations)
HP:0001004 (Lymphedema)
Neurologic Central Nervous System HP:0002326 (Transient ischemic attack)s
HP:0001297 (stroke)s
Seizures
HP:0002459 (Dysautonomia)
Peripheral Nervous System AcroHP:0003401 (Paresthesia)s, episodic
Pain and HP:0003401 (Paresthesia) in the extremities, episodic
Painful crises precipitated by exercise, fatigue, or stress
Hematology - HP:0001903 (Anemia)
Bone marrow contains lipid-laden macrophages
Laboratory Abnormalities - HP:0000093 (Proteinuria)
Alpha-galactosidase A deficiency in plasma, leukocytes, or fibroblasts
Increased level of globotriaosylceramide (GB3) in plasma and urinary sediment
Intracellular glycosphingolipid deposition in all tissues of the body
Increased plasma globotriaosylsphingosine (lyso-GB3)
Miscellaneous - Onset usually in childhood or adolescence
Death secondary to HP:0000083 (Renal failure), cardiac or cerebrovascular disease
Atypical affected males, 'cardiac variants' 301500.0005 exist
Female carriers experience significant clinical manifestations
Occurs in at least 1 in 55,000 male births (that figure may not include milder variants)
Bone marrow contains lipid-laden macrophages
Increased globotriaosylceramide (GB3) (P, U)
Increased globotriaosylsphingosine (lyso-GB3) (P)
GLB1 611458 GM1-GANGLIOSIDOSIS, TYPE II #230600   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Face Normal facies
Eyes HP:0000648 (optic atrophy)
Abdomen Liver No HP:0002240 (Hepatomegaly)
Spleen No HP:0001744 (Splenomegaly)
Skeletal Spine Mild HP:0000926 (Platyspondyly)
Pelvis HP:0002673 (Coxa valga)
Mild flaring of iliac wings
Neurologic Central Nervous System HP:0007281 (Developmental arrest), 2nd year of life
HP:0002123 (Myoclonic seizures)
Progressive psychoHP:0002333 (Motor deterioration)
Spastic HP:0002445 (quadriplegia)
HP:0001288 (Gait disturbance) (HP:0001251 (ataxia)
HP:0002283 (global brain atrophy)
HP:0002119 (ventriculomegaly)
Hematology - Sea-blue histiocyte (bone marrow)
Laboratory Abnormalities - Decreased beta-galactosidase activity (leukocyte, fibroblast, plasma)
Miscellaneous - Onset of disease 7 months to 3 years
Survival to 10 years
Glycosaminoglycans (U)
Oligosaccharides (U)
GLDC 238300 GLYCINE ENCEPHALOPATHY; GCE 605899   1 Inheritance - HP:0000007 (Autosomal recessive)
Neurologic Central Nervous System HP:0001274 (agenesis of corpus callosum) (variable)
HP:0001254 (Lethargy)
Seizures
HP:0100247 (Hiccups)
HP:0008947 (Hypotonia, early)
HP:0001265 (Hyporeflexia) to HP:0001347 (Hyperreflexia)
HP:0001336 (myoclonus)
HP:0001249 (Intellectual disability)
HP:0010851 (Burst suppression pattern) on neonatal EEG
Expressive speech deficit
Behavioral Psychiatric Manifestations HP:0000752 (Hyperactivity)
HP:0100710 (Impulsivity)
HP:0000718 (aggressive behavior)
HP:0000737 (Irritability)
HP:0000711 (Restlessness)
Laboratory Abnormalities - Hyperglycinemia
Hyperglycinuria
Hepatic glycine cleavage defect
Elevated CSF glycine
Elevated CSF/plasma glycine ratio
Miscellaneous - HP:0001522 (Death in infancy) common for patients with the classic neonatal form
Patients with atypical form have milder disease, with onset in the first months of life and increased survival
Hyperglycinemia
Hyperglycinuria
Increased CSF glycine
Increased CSF/plasma glycine ratio
GLI2 165230 HOLOPROSENCEPHALY 9; HPE9 #610829   2 Inheritance - HP:0000006 (Autosomal dominant)
Growth Height HP:0004322 (short stature) (in some patients)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0011800 (Midface hypoplasia)
First branchial arch anomalies
Temporomandibular joint abnormalities
Ears HP:0000377 (dysplastic ears)
Abnormal helix
Prominent antihelix
Hypoplastic tragus
First branchial arch anomalies
Eyes HP:0000568 (Microphthalmia)
HP:0000528 (Anophthalmia)
HP:0000609 (Optic nerve hypoplasia)
HP:0000601 (Hypotelorism)
Nose HP:0000431 (Broad nasal bridge)
Single nares
Mouth HP:0100333 (Unilateral cleft lip)
HP:0000175 (Cleft palate)
Teeth Solitary median maxillary central incisor
Genitourinary External Genitalia (Male) HP:0000054 (Small penis)
Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
Skeletal Hands HP:0001162 (Postaxial hand polydactyly)
HP:0001830 (Postaxial feet polydactyly)
Neurologic Central Nervous System HP:0001360 (holoprosencephaly)
HP:0001263 (Delayed psychomotor development)
Seizures
HP:0010627 (Anterior pituitary hypoplasia)
Endocrine Features - HP:0040075 (Hypopituitarism)
Miscellaneous - HP:0003812 (Variable phenotype)
HP:0003829 (Incomplete penetrance)
HP:0003828 (Variable expressivity)
 
GLI3 165240 Hypothalamic Hamartoma with Gelastic Epilepsy   27453577 2 Inheritance - HP:0000006 (Autosomal dominant)
Growth Height HP:0004322 (short stature)
Other HP:0001511 (Intrauterine growth retardation)
Head and Neck Ears HP:0000377 (Simple ears)
Absent external auditory canals
HP:0008551 (Microtia)
HP:0000358 (Posteriorly rotated ears)
Eyes HP:0000568 (Microphthalmia)
Nose HP:0003196 (Short nose)
HP:0000431 (Broad nasal bridge)
HP:0000463 (Anteverted nares)
Mouth Multiple buccal frenula
HP:0000171 (Microglossia)
HP:0100333 (Unilateral cleft lip) and palate
Teeth HP:0000695 (Neonatal teeth)
Cardiovascular Heart HP:0001629 (Ventricular septal defect)
Proximal HP:0001680 (Coarctation of aorta)
Vascular HP:0001643 (Patent ductus arteriosus)
Respiratory Larynx HP:0008751 (Laryngeal cleft)
HP:0010564 (Bifid epiglottis)
Hypoplastic epiglottis
Lung HP:0002101 (Abnormal lung lobation)
Chest Ribs, Sternum, Clavicles and Scapulae HP:0000902 (Fused ribs)
Abdomen Gastrointestinal HP:0002023 (anal atresia)
Genitourinary External Genitalia (Male) HP:0000054 (Small penis)
Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
HP:0008734 (Testicular hypoplasia)
Kidneys HP:0000110 (Renal dysplasia)
HP:0000086 (Renal ectopia)
Skeletal Spine HP:0002937 (Hemivertebrae)
Pelvis HP:0002827 (Hip dislocations)
Limbs HP:0006402 (Distal shortening of limbs)
Radial subluxation
Hands HP:0001162 (Postaxial hand polydactyly)
HP:0012165 (Oligodactyly)
HP:0010044 (Short 4th metacarpals)
HP:0006101 (Finger syndactyly)
Feet HP:0006101 (Finger syndactyly)
HP:0001162 (Postaxial hand polydactyly)
Skin, Nails, Hair Skin Midline facial capillary HP:0001028 (Hemangioma)
Nails HP:0002164 (dysplastic nails)
Neurologic Central Nervous System HP:0001360 (holoprosencephaly) (less common)
Hypothalamic hamartoma
Pituitary aplasia or dysplasia
Endocrine Features - PanHP:0040075 (Hypopituitarism)
Adrenal gland hypoplasia
Thyroid dysplasia/aplasia
Miscellaneous - HP:0003828 (Variable severity)
HP:0003828 (Variable expressivity)
 
GLRA1 138491 HYPEREKPLEXIA, HEREDITARY 1; HKPX1 #149400   2 0  
GLRB 138492 HYPEREKPLEXIA, HEREDITARY 1; HKPX1 614619   2 0  
GLUD1 138130 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 6; HHF6 #606762   3 Inheritance - HP:0000006 (Autosomal dominant)
Neurologic Central Nervous System HP:0002173 (Hypoglycemic seizures)
Loss of consciousness due to HP:0001943 (Hypoglycemia)
HP:0001249 (Intellectual disability) due to repeated episodes of HP:0001943 (Hypoglycemia)
Endocrine Features - Hyperinsulinemic HP:0001943 (Hypoglycemia)
Laboratory Abnormalities - HP:0001943 (Hypoglycemia)
HP:0000842 (Hyperinsulinemia)
HP:0001987 (hyperammonemia), asymptomatic (2-5 times normal)
Miscellaneous - Genetic heterogeneity (see HHF1 256450)
Mean age at onset of HP:0001943 (Hypoglycemia) may be delayed (median, 9 months, diagnosis sometimes made in adulthood)
Hyperinsulinemic hypoglycemia
Hyperammonemia
GLUL 138290 GLUTAMINE DEFICIENCY, CONGENITAL #610015   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Ears HP:0000369 (Low-set ears)
Nose Flat, HP:0000431 (Broad nasal bridge)
Cardiovascular Heart HP:0001662 (Bradycardia)
Respiratory - HP:0002093 (Respiratory insufficiency)
HP:0002104 (Apnea)
Skeletal - HP:0004576 (large joint contractures)
Limbs HP:0002983 (Micromelia)
Skin, Nails, Hair Skin Blistering erythematous HP:0000988 (rash)
Skin Histology Necrotic epidermolysis
Neurologic Central Nervous System HP:0004319 (nonprogressive encephalopathy)
HP:0008947 (Hypotonia, early)
Seizures
HP:0001263 (global developmental delay), severe
HP:0001347 (Hyperreflexia)
HP:0002283 (Generalized brain atrophy)
HP:0002079 (Thin corpus callosum)
HP:0002536 (Abnormal gyri)
Attenuated gyri
HP:0007109 (Periventricular cysts)
HP:0002416 (Subependymal cysts)
HP:0002119 (ventriculomegaly)
Small, smooth cerebellum
HP:0003429 (Hypomyelination)
Laboratory Abnormalities - Decreased glutamine in bodily fluids
HP:0001987 (hyperammonemia)
Miscellaneous - Three patients have been reported
Onset as neonate
HP:0001522 (Death in infancy) in 2 patients
HP:0003828 (Variable severity) of brain malformations
Decreased glutamine (P, U, C)
Hyperammonemia
GLYCTK 610516 D-GLYCERIC ACIDURIA 220120   1 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001510 (Growth delay)
HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000252 (microcephaly)
HP:0000407 (sensorineural hearing loss)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early), neonatal
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
HP:0001249 (Intellectual disability)
Axial HP:0008947 (Hypotonia, early)
Limb HP:0001257 (Spasticity)
HP:0001347 (Hyperreflexia)
Spastic HP:0002445 (Tetraplegia)
Seizures, refractory
HP:0002179 (Opisthotonus)
HP:0001336 (myoclonus)
HP:0004319 (nonprogressive encephalopathy)
HP:0002521 (hypsarrhythmia)
HP:0002120 (Cortical atrophy)
Periventricular and subcortical HP:0002500 (White matter abnormalities)
HP:0012448 (Delayed myelination)
Behavioral Psychiatric Manifestations HP:0000729 (autistic behaviour)
Metabolic Features - HP:0001942 (metabolic acidosis)
Laboratory Abnormalities - Increased D-glyceric acid in serum, urine, and CSF
Hyperglycinemia
Miscellaneous - HP:0003812 (Variable phenotype)
Some patients have no or mild manifestations and normal development
HP:0003577 (Onset at birth) or in infancy
Increased D-glyceric acid (P, U, C)
Hyperglycinemia
GM2A 613109 GM2-GANGLIOSIDOSIS, AB VARIANT     2 Eyes Cherry red macula
Gray-white area around the retinal fovea
HP:0000618 (Blindness)
Neuro HP:0002267 (Hyperekplexia)
HP:0008947 (Hypotonia, early)
Late HP:0001276 (Muscle hypertonia)
HP:0002421 (Poor head control)
HP:0000741 (Apathy)
HP:0001263 (global developmental delay)
Seizures
Paralysis
HP:0000726 (Dementia)
Resp HP:0002835 (Aspiration)
Lab Gm2-ganglioside accumulation
Both Hexosaminidase-A and B present
Hex-A activating factor defect
Oligosaccharides (U)
GMPPB 615320 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH MENTAL RETARDATION), TYPE B, 14; MDDGB14 #615351   4 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly)
HP:0002421 (Poor head control)
Face HP:0002058 (Myopathic facies)
Eyes HP:0000518 (Cataracts) (in some patients)
HP:0000486 (Strabismus) (in some patients)
HP:0000508 (Ptosis) (in some patients)
HP:0000639 (Nystagmus) (in some patients)
Cardiovascular Heart HP:0001657 (Long QT syndrome)
Left HP:0002119 (Ventriculomegaly)
Abdomen Gastrointestinal HP:0011968 (feeding difficulties)
Skeletal - HP:0004576 (large joint contractures) (in some patients)
Muscle, Soft Tissue - HP:0003560 (Muscular dystrophy)
HP:0008947 (Hypotonia, early)
HP:0003324 (Muscle weakness), severe
Generalized HP:0003202 (Muscle wasting)
HP:0001276 (Hypertonicity) (early in life)
Dystrophic features seen on muscle biopsy
Hypoglycosylation of alpha-dystroglycan seen on muscle biopsy
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
HP:0001249 (Intellectual disability), mild to severe
HP:0001344 (absent speech)
Delayed or absent independent walking
Seizures (in some patients)
HP:0001321 (Cerebellar hypoplasia) (in some patients)
Prenatal Manifestations Movement HP:0001558 (Decreased fetal movement)
Laboratory Abnormalities - HP:0003236 (Increased serum creatine kinase)
Miscellaneous - HP:0003577 (Onset at birth) or in early infancy
HP:0003828 (Variable severity)
Increased serum creatine kinase
GNAO1 139311 EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 17; EIEE17 #615473   1 Inheritance - HP:0000006 (Autosomal dominant)
Neurologic Central Nervous System Epileptic HP:0004319 (nonprogressive encephalopathy)
HP:0001263 (Lack of psychomotor development)
HP:0001344 (absent speech)
Seizures, intractable
Tonic seizures
EEG shows suppression-burst pattern
HP:0002521 (hypsarrhythmia)
Multifocal spike waves
HP:0007325 (generalized dystonia) (in some patients)
HP:0002072 (Chorea) (in some patients)
HP:0002305 (Athetosis) (in some patients)
HP:0002283 (global brain atrophy)
HP:0002079 (Thin corpus callosum)
HP:0012448 (Delayed myelination)
Miscellaneous - Onset in early infancy
De novo mutation
 
GNAQ 600998 STURGE-WEBER SYNDROME; SWS #185300    2 Inheritance - HP:0003745 (Isolated cases)
Head and Neck Head HP:0000256 (Macrocephaly)
Face Facial HP:0001028 (Hemangioma)ta
Eyes Choroidal HP:0001028 (Hemangioma)ta
HP:0000501 (Glaucoma)
HP:0000557 (Buphthalmos)
Skin, Nails, Hair Skin HP:0001028 (Hemangioma)ta in at least first branch (ophthalmic) of trigeminal nerve distribution, unilateral, occasionally bilateral
Neurologic Central Nervous System Arachnoid HP:0001028 (Hemangioma)ta
Cerebral HP:0002120 (Cortical atrophy)
HP:0001249 (Intellectual disability)
Seizures
'Double contour' convolutional calcification on CT scan
 
GNAS 139320 PSEUDOHYPOPARATHYROIDISM, TYPE IB; PHP1B #603233 25943944 4 Inheritance - HP:0000006 (Autosomal dominant)
Skeletal - Osteitis fibrosa cystica due to elevated parathyroid hormone (PTH) (subset of patients)
Endocrine Features - Renal resistance to PTH
PseudoHP:0000829 (Hypoparathyroidism)
Laboratory Abnormalities - Elevated serum PTH
HP:0002901 (hypocalcemia)
HP:0002905 (Hyperphosphatemia)
Normal erythrocyte Gs activity
Low urinary cyclic AMP response to PTH administration
Miscellaneous - Many cases result from de novo mutations
Endocrine abnormalities confined to kidney
Typically no physical features of Albright hereditary osteodystrophy (AHO)
Features of AHO may rarely be observed, including HP:0009803 (short fingers), HP:0010049 (HP:0010049 (Short metacarpals), and HP:0001513 (Obesity) (see 103580)
Associated with imprinting and epigenetic defects in the G-protein, alpha-stimulating 1 gene (GNAS1, 139320)
See also pseudoHP:0000829 (Hypoparathyroidism) type Ia (PHP1A, 103580)
 
GNASAS1 610540 PSEUDOHYPOPARATHYROIDISM, TYPE IB; PHP1B #603233   4 Inheritance - HP:0000006 (Autosomal dominant)
Skeletal - Osteitis fibrosa cystica due to elevated parathyroid hormone (PTH) (subset of patients)
Endocrine Features - Renal resistance to PTH
PseudoHP:0000829 (Hypoparathyroidism)
Laboratory Abnormalities - Elevated serum PTH
HP:0002901 (hypocalcemia)
HP:0002905 (Hyperphosphatemia)
Normal erythrocyte Gs activity
Low urinary cyclic AMP response to PTH administration
Miscellaneous - Many cases result from de novo mutations
Endocrine abnormalities confined to kidney
Typically no physical features of Albright hereditary osteodystrophy (AHO)
Features of AHO may rarely be observed, including HP:0009803 (short fingers), HP:0010049 (HP:0010049 (Short metacarpals), and HP:0001513 (Obesity) (see 103580)
Associated with imprinting and epigenetic defects in the G-protein, alpha-stimulating 1 gene (GNAS1, 139320)
See also pseudoHP:0000829 (Hypoparathyroidism) type Ia (PHP1A, 103580)
 
GNE 603824 SIALURIA #269921   2 Inheritance - HP:0000006 (Autosomal dominant)
Growth Other Normal growth
Head and Neck Face HP:0000280 (Coarse facies)
HP:0011220 (Prominent forehead)
Long, HP:0000319 (smooth philtrum)
Ears HP:0000369 (Low-set ears)
Eyes HP:0000664 (Synophrys)
HP:0000286 (Epicanthus)
HP:0000316 (Hypertelorism)
HP:0000629 (Periorbital fullness)
Nose HP:0007965 (Broad nasal bridge)
HP:0000218 (High-arched palate)
HP:0000219 (Thin upper lip)
Respiratory - HP:0010535 (sleep apnea)
Chest External Features Small chest
Breasts HP:0002557 (Hypoplastic nipples)
Abdomen External Features HP:0001538 (Protuberant abdomen)
Liver HP:0002240 (Hepatomegaly)
Spleen HP:0001744 (Splenomegaly)
Genitourinary External Genitalia (Male) Inguinal HP:0100790 (Hernias)
Skeletal Spine HP:0002650 (Scoliosis)
Feet Large halluces
2,3 toe HP:0006101 (Finger syndactyly)
Skin, Nails, Hair Hair HP:0002162 (Low posterior hairline)
Generalized HP:0001007 (Hirsutism)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
Seizures
HP:0007018 (Attention deficit hyperactivity disorder) disorder
Laboratory Abnormalities - Elevated urinary free sialic acid (N-acetylneuraminic acid)
Elevated fibroblast free sialic acid
Increased free sialic acid (N-acetylneuraminic acid) (U)
GNS 607664 MUCOPOLYSACCHARIDOSIS, TYPE IIID; MPS3D #252940   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height Normal stature
Head and Neck Face HP:0000280 (Coarse facies)
HP:0011220 (Prominent forehead)
EarsHP:0000410 (Hearing loss, mixed)
HP:0000369 (Low-set ears)
Eyes Clear corneas
HP:0000664 (Synophrys)
HP:0000505 (Visual impairment)
Nose HP:0000431 (Broad nasal bridge)
HP:0000463 (Anteverted nares)
Mouth HP:0012471 (Thick lips)
HP:0000154 (Wide mouth)
HP:0002307 (Drooling)
Neck HP:0000470 (Short neck)
Cardiovascular Heart HP:0001670 (Asymmetric septal hypertrophy)
Respiratory Nasopharynx HP:0002788 (Recurrent upper respiratory tract infections)
Chest Ribs, Sternum, Clavicles and Scapulae Thick ribs
Abdomen Liver Mild HP:0002240 (Hepatomegaly)
Spleen Mild HP:0001744 (Splenomegaly)
Gastrointestinal HP:0002014 (Diarrhea)
HP:0002015 (Dysphagia)
HP:0002307 (Drooling)
Skeletal - Mild dysotosis multiplex
Joint HP:0004576 (large joint contractures)
Spine HP:0003309 (Ovoid thoracolumbar vertebrae)
Limbs Mild HP:0001387 (joint stiffness)
Skin, Nails, Hair Hair HP:0001007 (Hirsutism)
HP:0002208 (Coarse hair)
HP:0000574 (Thick eyebrows)
HP:0000664 (Synophrys)
Neurologic Central Nervous System HP:0001249 (Intellectual disability)
HP:0000752 (Hyperactivity)
Seizures
HP:0001344 (absent speech)
HP:0001260 (Dysarthria)
Slowing mental development by 1.5 to 3 years of age
HP:0002360 (Sleep disturbance) common
Behavioral Psychiatric Manifestations Severe HP:0000708 (behavioral disturbance) beginning at 3 to 4 years of age
Laboratory Abnormalities - N-acetylglucosamine-6-sulfate sulfatase deficiency
Heparan sulfate excretion in urine
Metachromasia of white blood cells and fibroblasts
Miscellaneous - Four clinically indistinguishable biochemically distinct forms (see 252900, 252920, 252930)
HP:0003676 (Progressive disorder)
Heparan sulfate (U)
GOSR2 604027 EPILEPSY, PROGRESSIVE MYOCLONIC, 6; EPM6 #614018   2 Inheritance - HP:0000007 (Autosomal recessive)
Skeletal Spine HP:0002650 (Scoliosis)
Neurologic Central Nervous System HP:0001251 (ataxia)
HP:0002355 (Difficulty walking)
Action HP:0001336 (myoclonus)
Seizures
HP:0002069 (Tonic-clonic seizures)
HP:0002121 (Absence seizures)
HP:0010819 (atonic seizures)
HP:0001260 (Dysarthria)
HP:0001284 (Areflexia)
HP:0002322 (Resting tremor), variable
Active generalized spike and wave and polyspike pattern seen on EEG
HP:0000992 (Photosensitivity) seen on EEG
Mild HP:0100543 (Cognitive impairment) (in 2 patients)
Laboratory Abnormalities - HP:0003236 (Increased serum creatine kinase) (in some patients)
Miscellaneous - Onset of HP:0001251 (ataxia) between 1 and 3 years of age
Onset of HP:0001336 (myoclonus) later in childhood
HP:0003676 (Progressive disorder)
Some patients become wheelchair-bound in second decade
 
GPHN 603930 MOLYBDENUM COFACTOR DEFICIENCY, COMPLEMENTATION GROUP C; MOCODC 615501   1 0 Positive sulfite test
Increased S-sulfocysteine (U)
Increased taurine (U)
GPSM2 609245 CHUDLEY-MCCULLOUGH SYNDROME; CMCS 604213   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000238 (Hydrocephalus) (variable)
Ears HP:0000407 (sensorineural hearing loss), severe-to-profound
Neurologic Central Nervous System HP:0000238 (Hydrocephalus) (variable)
HP:0002119 (ventriculomegaly) (variable)
Normal psychomotor development in most
HP:0001249 (Intellectual disability), mild (uncommon)
Seizures (uncommon)
Brain MRI shows HP:0002079 (Hypoplasia of the corpus callosum)
Partial HP:0001274 (agenesis of corpus callosum)
HP:0006989 (Dysplastic corpus callosum)
HP:0001321 (Cerebellar hypoplasia) due to enlarged foramen magnum
Focal HP:0007033 (Cerebellar dysplasia)
Obstruction of the foramen of Monro (variable)
Subcortical nodular grey matter HP:0002282 (heterotopia)
HP:0002126 (Polymicrogyria)
HP:0100702 (Arachnoid cysts)
Miscellaneous -HP:0000410 (Hearing loss, mixed) may be congenital or rapidly progressive leading to severeHP:0000410 (Hearing loss, mixed) by age 3 years
 
GPT2 138210 MENTAL RETARDATION, AUTOSOMAL RECESSIVE 49; MRT49 616281   2 0 0
GRIA3 305915 MENTAL RETARDATION, X-LINKED, SYNDROMIC, WU TYPE; MRXSW #300699    2 Inheritance - HP:0001419 (X-linked recessive)
Growth Height HP:0004322 (short stature)
Other Asthenic body habitus
Head and Neck Head HP:0000248 (Brachycephaly)
HP:0000256 (Macrocephaly)
Face HP:0001999 (Dysmorphic features)
Eyes HP:0000336 (Prominent supraorbital ridges)
HP:0000490 (Deep-set eyes)
Muscle, Soft Tissue - HP:0003199 (Decreased muscle mass)
Neurologic Central Nervous System HP:0001249 (Intellectual disability), severe
Seizures
HP:0001336 (myoclonus)
Peripheral Nervous System HP:0001265 (Hyporeflexia)
Behavioral Psychiatric Manifestations HP:0000729 (autistic behaviour)
HP:0000718 (Aggressive behavior)
HP:0100716 (Self-injurious behavior)
Miscellaneous - Variable features
 
GRIK2 138244 MENTAL RETARDATION, AUTOSOMAL RECESSIVE 6; MRT6 611092   2 Inheritance - HP:0000007 (Autosomal recessive)
Neurologic Central Nervous System HP:0001263 (global developmental delay)
HP:0001249 (Intellectual disability)
Seizures (in some patients)
HP:0002375 (Involuntary movements)
HP:0001336 (myoclonus)
HP:0007325 (generalized dystonia)
HP:0002322 (Resting tremor)
Miscellaneous - HP:0003593 (Onset in infancy)
 
GRIN1 138249 MENTAL RETARDATION, AUTOSOMAL DOMINANT 8; MRD8 #614254    2 0  
GRIN2A 138253 EPILEPSY, FOCAL, WITH SPEECH DISORDER AND WITH OR WITHOUT MENTAL RETARDATION; FESD #245570   2 Inheritance - HP:0000006 (Autosomal dominant)
Neurologic Central Nervous System HP:0001263 (Global developmental delay) (in some patients)
HP:0001249 (Intellectual disability) (in some patients)
HP:0001328 (Specific learning disability)
Seizures, focal
Rolandic epilepsy
Speech and language difficulties
HP:0011098 (Speech apraxia)
HP:0002357 (Dysphasia)
Secondary seizures (in some patients)
Other seizure types (in some patients)
EEG shows centrotemporal spike-wave discharges
Continuous spike-waves during slow-wave sleep
Behavioral Psychiatric Manifestations HP:0000729 (autistic behaviour)
HP:0007018 (Attention deficit hyperactivity disorder)
Miscellaneous - Onset of seizures in infancy or early childhood
Seizures may remit in adolescence
Highly HP:0003828 (Variable severity)
HP:0003829 (Incomplete penetrance)
 
GRIN2B 138252 EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 27; EIEE27 #616139   1 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Eyes Poor visual contact
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Axial muscle hyperextension, episodic
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
Epileptic HP:0004319 (nonprogressive encephalopathy)
Seizures
HP:0001249 (Intellectual disability)
HP:0008947 (Hypotonia, early)
Inability to sit
HP:0001344 (absent speech)
HP:0002521 (hypsarrhythmia) seen on EEG
Miscellaneous - Onset in first weeks or months of life
Two unrelated patients with epileptic HP:0004319 (nonprogressive encephalopathy) have been reported
HP:0003828 (Variable severity)
 
GRM1 604473 SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 13; SCAR13 614831   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature) (adults)
Head and Neck Eyes Horizontal HP:0000639 (Nystagmus) (about half of patients)
HP:0000571 (Hypometric saccades) (about half of patients)
Abduction deficits (about half of patients)
HP:0000565 (Esotropia) (about half of patients)
HP:0000508 (Ptosis) (about half of patients)
Skeletal Feet HP:0001763 (pes planus)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
HP:0001249 (Intellectual disability), mild to profound
HP:0001344 (absent speech) development (some patients)
HP:0002540 (Inability to walk) (some patients)
cerebellar HP:0001251 (ataxia), gait and stance
HP:0001260 (Dysarthria)
HP:0001310 (Dysmetria)
HP:0002322 (Resting tremor), mild
HP:0002075 (Dysdiadochokinesis)
HP:0001347 (Hyperreflexia)
Seizures (some patients)
HP:0007256 (Pyramidal tract signs), mild (uncommon)
HP:0001272 (Cerebellar atrophy)
Inferior HP:0006817 (Aplasia/Hypoplasia of the cerebellar vermis)
HP:0002119 (ventriculomegaly)
RetroHP:0002350 (Cerebellar cysts)
Small brain size (some patients)
Miscellaneous - HP:0003593 (Onset in infancy)
Slowly progressive
Observed in individuals of Bulgarian Roma Bowlmaker ethnic group
 
GRN 138945 CEROID LIPOFUSCINOSIS, NEURONAL, 11; CLN11 #614706   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes HP:0000505 (Visual impairment), progressive
HP:0000648 (optic atrophy)
HP:0000556 (Retinal dystrophy)
Neurologic Central Nervous System Seizures
HP:0002123 (Myoclonic seizures)
HP:0001251 (ataxia)
HP:0001268 (cognitive decline)
EEG abnormalities
HP:0001272 (Cerebellar atrophy)
Laboratory Abnormalities - 'Fingerprint' profiles ultrastructurally
Miscellaneous - Onset in early twenties
Rapidly progressive
Fingerprint' profiles ultrastructurally
GSS 601002 GLUTATHIONE SYNTHETASE DEFICIENCY; GSSD 266130   2 Eyes Peripheral retinal pigmentation abnormalities
Neuro HP:0001249 (Intellectual disability)
HP:0001251 (ataxia)
Seizures
Spastic HP:0030182 (Tetraparesis/tetraplegia)
Intention HP:0002322 (Resting tremor)
HP:0001260 (Dysarthria)
HP:0000709 (psychosis)
Inheritance HP:0000007 (Autosomal recessive)
Metabolic Chronic HP:0001942 (metabolic acidosis)
Lab Pyroglutamic acidemia
Pyroglutamic aciduria
Decreased erythrocyte glutathione
Glutathione synthetase deficiency
Increased gamma-glutamyl-cysteine synthetase
Neutrophil bactericidal and iodination defects responsive to vitamin E (alpha-tocopherol)
Heme Increased hemolysis
Mild hemolytic HP:0001903 (Anemia)
Episodic HP:0001875 (Neutropenia)
Pyroglutamic acidemia
Pyroglutamic aciduria
Decreased erythrocyte glutathione
GTPBP3 608536 COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 23; COXPD23 616198   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001511 (Intrauterine growth retardation)
Head and Neck Eyes HP:0000505 (Visual impairment) (in some patients)
Cardiovascular Heart HP:0001638 (Cardiomyopathy)
HP:0001635 (Cardiac failure)s
Arrhythmia
Abdomen Gastrointestinal HP:0011968 (feeding difficulties)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Decreased activity of mitochondrial complexes I and IV seen on skeletal muscle biopsy
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development), variable
Seizures (in some patients)
T2-weighted hyperintense lesions in the thalamus, basal ganglia, and brainstem
Metabolic Features - HP:0003128 (Lactic acidosis)
Laboratory Abnormalities - HP:0002151 (Increased serum lactate)
Miscellaneous - Onset in early childhood
HP:0003828 (Variable severity)
Increased lactate (P)
GUCY1A3 139396 MOYAMOYA DISEASE 6 WITH ACHALASIA; MYMY6 615750   4 Inheritance - HP:0000007 (Autosomal recessive)
Cardiovascular Vascular Moyamoya disease
Stenosis of the intracranial arteries
Ischemic HP:0001297 (stroke) (in some patients)
HP:0000822 (Hypertension) (in some patients)
Raynaud phenomenon (in some patients)
Abdomen Gastrointestinal HP:0002571 (achalasia)
HP:0002015 (Dysphagia)
Genitourinary External Genitalia (Male) HP:0000802 (impotence)
Skin, Nails, Hair Skin HP:0000965 (Livedo reticularis)
Raynaud phenomenon (in some patients)
Neurologic Central Nervous System Ischemic HP:0001297 (stroke) (in some patients)
HP:0001269 (Hemiparesis) (in some patients)
Seizures
Miscellaneous - Onset of HP:0002571 (achalasia) in infancy or early childhood
Some patients do not develop HP:0001297 (stroke)
HP:0003828 (Variable severity)
 
GYS1 138570 GLYCOGEN STORAGE DISEASE 0, MUSCLE; GSD0B #611556   4 Inheritance - HP:0000007 (Autosomal recessive)
Cardiovascular Heart HP:0001712 (Left ventricular hypertrophy)
Left atrial enlargement
Decrease in stroke volume on exercise testing
Myocyte hypertrophy without disarray or fibrosis seen on biopsy
Lack of glycogen in cardiomyocytes
Abdomen Liver Glycogen present in normal amount on biopsy
Muscle, Soft Tissue - Muscle fatigability
Low maximum workload on exercise testing
Glycogen deficiency in muscle fibers
Predominance of oxidative fibers
Mitochondrial proliferation
Neurologic Central Nervous System HP:0002069 (tonic-clonic seizures) (rare)
Miscellaneous - Risk of HP:0001699 (Sudden death) in childhood due to cardiac arrest
0
GYS2 138571 GLYCOGEN STORAGE DISEASE 0, LIVER; GSD0A 240600   3 Inheritance HP:0000007 (Autosomal recessive)
Neuro Seizures
Lab Glycogen synthetase deficiency
Metabolic Neonatal HP:0001943 (Hypoglycemia)
Fasting HP:0001943 (Hypoglycemia)
Fasting hyperHP:0001946 (ketosis)
HP:0003074 (Hyperglycemia) and hyperlactatemia with feeding
Neonatal hypoglycemia
Fasting hypoglycemia
Fasting hyperketonemia
Hyperglycemia and hyperlactatemia with feeding
HADH 601609 3-HYDROXYACYL-CoA DEHYDROGENASE DEFICIENCY #231530   3 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001510 (Growth delay)
Cardiovascular Heart HP:0001644 (dilated cardiomyopathy)
HP:0001639 (hypertrophic cardiomyopathy)
Abdomen Liver HP:0002605 (Liver necrosis)
HP:0001397 (Liver steatosis)
Fulminant HP:0001399 (Liver failure)
Gastrointestinal HP:0011968 (feeding difficulties)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System HP:0002173 (Hypoglycemic seizures)
HP:0004319 (nonprogressive encephalopathy), hypoglycemic
Metabolic Features - HP:0001943 (Hypoglycemia), hypoketotic
Laboratory Abnormalities - HP:0001943 (Hypoglycemia)
HP:0002913 (Myoglobinuria)
HP:0003215 (dicarboxylic aciduria)
Decreased activity of 3-hydroxyacyl-CoA dehydrogenase in various tissues (liver, muscle, fibroblasts)
Some tissues may have normal levels of 3-hydroxyacyl-CoA dehydrogenase activity
Miscellaneous - HP:0003812 (Variable phenotype)
Sudden infant death may occur
Dicarboxylic aciduria
HAX1 605998 NEUTROPENIA, SEVERE CONGENITAL, 3, AUTOSOMAL RECESSIVE; SCN3 #610738   4 Inheritance - HP:0000007 (Autosomal recessive)
Neurologic Central Nervous System HP:0001263 (global developmental delay) (in some patients)
Seizures (in some patients)
Immunology - HP:0001875 (Neutropenia)
HP:0002718 (Recurrent bacterial infections)
Neoplasia - Increased risk of myelodysplastic syndromes
Increased risk of leukemia
Miscellaneous - HP:0003593 (Onset in infancy)
Only some patients showed neurologic involvement
 
HCCS 300056 LINEAR SKIN DEFECTS WITH MULTIPLE CONGENITAL ANOMALIES 1; LSDMCA1 309801   2 Inheritance - HP:0001423 (X-linked dominant)
Growth Height HP:0004322 (short stature) (3rd-10th percentile)
Head and Neck Head HP:0000252 (microcephaly)
EarsHP:0000410 (Hearing loss, mixed)
Eyes HP:0000568 (Microphthalmia)
HP:0000647 (Sclerocornea)
HP:0000518 (Cataracts)
Iris HP:0000589 (coloboma)
HP:0000580 (Pigmentary retinopathy)
Cardiovascular Heart HP:0001631 (Atrial septal defect)
HP:0001629 (Ventricular septal defect)
HP:0011675 (Arrhythmia)
Oncocytic HP:0001638 (Cardiomyopathy)
Vascular HP:0002623 (Overriding aorta)
Chest Diaphragm HP:0000776 (Diaphragmatic hernia)
Abdomen Gastrointestinal HP:0001545 (Anteriorly placed anus)
HP:0002023 (anal atresia)
Genitourinary External Genitalia (Male) HP:0000054 (Small penis)
HP:0000047 (Hypospadias)
Chordee
External Genitalia (Female) HP:0008665 (Clitoral hypertrophy)
Internal Genitalia (Female) HP:0000013 (Hypoplasia of the uterus)
HP:0012861 (Ovotestis)
Skin, Nails, Hair Skin HP:0007398 (Asymmetric, linear skin defects) (anterior face and neck)
Neurologic Central Nervous System HP:0001274 (Agenesis of corpus callosum)
HP:0001331 (Absence of septum pellucidum)
HP:0000238 (Hydrocephalus)
Mild to severe HP:0001249 (Intellectual disability) (24%)
Infantile seizures
HP:0030048 (Colpocephaly)
Laboratory Abnormalities - Distal Xp22.3 segmental monosomy
Miscellaneous - The acronym MIDAS is HP:0000568 (Microphthalmia), Dermal Aplasia, HP:0000647 (Sclerocornea)
 
HCFC1 300019 METHYLMALONIC ACIDEMIA AND HOMOCYSTEINEMIA, cblX TYPE #309541   1 Inheritance - HP:0001419 (X-linked recessive)
Growth Height HP:0004322 (short stature)
Other HP:0001508 (Failure to thrive)
Head and Neck Head HP:0000252 (microcephaly)
HP:0000248 (Brachycephaly)
Neurologic Central Nervous System Severely HP:0001263 (Delayed psychomotor development)
HP:0001249 (Intellectual disability)
Seizures, intractable
HP:0008947 (Hypotonia, early)
HP:0002521 (hypsarrhythmia)
HP:0002072 (Chorea) (in some patients)
HP:0002305 (Athetosis) (in some patients)
Laboratory Abnormalities - Methylmalonic aciduria
Methylmalonic acidemia
Homocystinuria (in some patients)
Homocysteinemia (in some patients)
Miscellaneous - HP:0003593 (Onset in infancy)
Methylmalonic acid U, P)
Homocysteine (P, U)
HCN1 602780 EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 24; EIEE24 #615871   1 Inheritance - HP:0000006 (Autosomal dominant)
Neurologic Central Nervous System Epileptic HP:0004319 (nonprogressive encephalopathy)
HP:0001249 (Intellectual disability)
Intractable seizures
HP:0002373 (febrile seizures)
HP:0001251 (ataxia) (in some patients)
Behavioral Psychiatric Manifestations HP:0000708 (Behavioral disturbance)
HP:0000729 (autistic behaviour)
Miscellaneous - Onset usually in the first year of life
Seizures tend to become more focal with age
 
HCN2 602781 Idiopathic generalized epilepsy   22131395 2 0  
HDAC1 601241 Epilepsy   26795593 2 0  
HDAC3 605166     26795593 2 0  
HEPACAM 611642 MEGALENCEPHALIC LEUKOENCEPHALOPATHY WITH SUBCORTICAL CYSTS 2A; MLC2A 613925   5 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000256 (Macrocephaly)
Neurologic Central Nervous System HP:0001355 (Megalencephaly)
HP:0001270 (Delayed motor development)
HP:0002344 (Neurologic deterioration)
HP:0001251 (ataxia)
HP:0001257 (Spasticity)
HP:0001276 (Muscle hypertonia)
Seizures
HP:0001268 (cognitive decline)
HP:0001249 (Intellectual disability)
HP:0001260 (Dysarthria)
Diffuse HP:0002500 (White matter abnormalities) on brain MRI
Diffuse swelling of cerebral white matter
HP:0002389 (Cavum septi pellucidi)
Cavum Vergae
Subcortical cysts in frontal and temporal lobes
Subcortical cysts may occur elsewhere
HP:0002283 (global brain atrophy)
HP:0001272 (Cerebellar atrophy)
HP:0002119 (ventriculomegaly)
Miscellaneous - Brainstem, cerebellum, internal and external capsule, inner rim of the corpus callosum may show disease involvement on MRI
Onset of HP:0000256 (Macrocephaly) in the first year of life
Slowly progressive
Most patients become wheelchair-bound in later childhood
 
HERC2 605837 MENTAL RETARDATION, AUTOSOMAL RECESSIVE 38; MRT38 615516   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0001357 (Plagiocephaly)
Face HP:0000303 (Prognathism)
Eyes Blue irides
HP:0000486 (Strabismus)
Mouth HP:0000189 (Narrow palate)
Skeletal Feet HP:0001852 (Sandal gap)
Pronation of the feet
Elongated hallux
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
HP:0001249 (Intellectual disability)
Delayed ambulation
Delayed adaptive hand use
HP:0000750 (Language delay)
Seizures (in some patients)
HP:0002317 (Unsteady gait)
HP:0002079 (Hypoplasia of corpus callosum) (in some patients)
Behavioral Psychiatric Manifestations HP:0000729 (autistic behaviour)
HP:0000752 (Hyperactivity)
Poor concentration
HP:0000718 (Aggressive behavior)
HP:0000742 (Self-mutilation)
HP:0100710 (impulsivity)
Miscellaneous - HP:0003593 (Onset in infancy)
Reported in individuals of Amish or Mennonite descent
 
HESX1 601802 SEPTOOPTIC DYSPLASIA 182230 21037540 3 inheritance - HP:0000006 (Autosomal dominant)
HP:0000007 (Autosomal recessive)
Growth Height HP:0004322 (short stature) (if untreated)
Head and Neck Eyes HP:0000609 (Optic nerve hypoplasia)
Hypoplastic optic discs
Skeletal Hands Polydactyly
Hypoplastic digits
Neurologic Central Nervous System HP:0001331 (Absence of septum pellucidum)
HP:0001274 (agenesis of corpus callosum)
Midline forebrain defects
HP:0001263 (global developmental delay)
Metabolic Features - HP:0001943 (Hypoglycemia), neonatal (in some patients)
Endocrine Features - HP:0010627 (Hypoplasia of pituitary gland)
Ectopic or absent posterior pituitary
HP:0000873 (Diabetes insipidus)
Laboratory Abnormalities - Low or absent growth hormone (GH)
Low or absent thyrotropin (TSH)
Low or absent follicle-stimulating hormone (FSH)
Low or absent luteinizing hormone (LH)
Low or absent adrenocorticotropic hormone (ACTH)
Miscellaneous - HP:0003812 (Variable phenotype)
Diagnosis made when at least 2/3 features present (HP:0000609 (Optic nerve hypoplasia), HP:0040075 (Hypopituitarism) with HP:0010627 (Anterior pituitary hypoplasia), midline forebrain defects)
 
HEXA 606869 TAY-SACHS DISEASE; TSD #272800   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Eyes Macular pallor with prominence of fovea centralis (HP:0010729 (cherry red spot)
HP:0000618 (Blindness)
Respiratory Airways HP:0002835 (Aspiration)
Neurologic Central Nervous System HP:0002267 (Hyperekplexia)
HP:0008947 (Hypotonia, early)
Late HP:0001276 (Muscle hypertonia)
HP:0002421 (Poor head control)
HP:0002361 (Psychomotor deterioration)
Seizures
HP:0000726 (Dementia)
Behavioral Psychiatric Manifestations HP:0000741 (Apathy)
Laboratory Abnormalities - Gm2-ganglioside accumulation
Ballooned neurons
Hexosaminidase A deficiency
Miscellaneous - Infantile onset
Usually fatal by age 5 years
Incidence of 1 in 3,900 births among Jewish persons
Incidence of 1 in 320,000 births among non-Jewish persons
Gm2-ganglioside
Ballooned neurons
HEXB 606873 SANDHOFF DISEASE #268800   2 GU HP:0000802 (Impotence)
Mild HP:0000020 (Urinary incontinence)
Neuro HP:0002267 (Hyperekplexia)
Progressive mental and HP:0002333 (Motor deterioration)
cerebellar HP:0001251 (ataxia)
HP:0001260 (Dysarthria)
HP:0002380 (Fasciculations)
HP:0002493 (Pyramidal tract dysfunction)
HP:0001347 (Hyperreflexia)
Impaired thermal sensitivity
HP:0001278 (Orthostatic hypotension)
Postural dizziness
Inheritance HP:0000007 (Autosomal recessive) with multiple alleles and compounds
Skel High HP:0008454 (lumbar gibbus)
Lab Hexosaminidase B beta chain deficiency
Tongue HP:0000158 (Macroglossia)
Muscle Infantile HP:0003324 (Muscle weakness)
HP:0003202 (Muscle wasting)
GI Chronic HP:0002014 (Diarrhea)
Episodic HP:0002027 (Abdominal pain)
HepatoHP:0001744 (Splenomegaly)
Eyes Early HP:0000618 (Blindness)
HP:0010729 (cherry red spot)s
Facies Doll-like face
HP:0000280 (Coarse facies)
Misc Lethal usually by age 3 years
Intolerance to heat
Cranium HP:0000256 (Macrocephaly)
Skin HP:0000971 (Abnormalities of sweating)
Cardiac HP:0001640 (Cardiomegaly)
 
HGSNAT 610453 MUCOPOLYSACCHARIDOSIS, TYPE IIIC; MPS3C #252930   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other Usually normal stature
Head and Neck Face HP:0000280 (Coarse facies), mild
EarsHP:0000410 (Hearing loss, mixed)
Thickening of the helices
Eyes Clear corneas
HP:0000664 (Synophrys)
HP:0000510 (Retinitis pigmentosa) (late-onset)
Nose Fleshy nasal tip
Mouth HP:0000179 (Thick lower lip vermilion)
Cardiovascular Heart HP:0001670 (Asymmetric septal hypertrophy)
Respiratory Nasopharynx HP:0002788 (Frequent upper respiratory infections)
Chest Ribs, Sternum, Clavicles and Scapulae Thickened ribs
Abdomen Liver Mild HP:0002240 (Hepatomegaly)
Spleen Mild HP:0001744 (Splenomegaly)
Gastrointestinal HP:0002014 (Diarrhea)
HP:0002015 (Dysphagia)
Skeletal - Mild HP:0000943 (dysostosis multiplex)
Skull HP:0000250 (Dense calvaria)
HP:0000268 (Dolichocephaly)
Spine HP:0003309 (Ovoid thoracolumbar vertebrae)
HP:0002751 (kyphoscoliosis)
Limbs Mild HP:0001387 (joint stiffness)
Skin, Nails, Hair Hair HP:0000664 (Synophrys)
HP:0001007 (Hirsutism)
HP:0002208 (Coarse hair)
Muscle, Soft Tissue - HP:0100790 (Hernias)
Neurologic Central Nervous System HP:0001249 (Intellectual disability)
Slowing mental development by 1.5 to 3 years of age
HP:0002360 (Sleep disturbance) common
HP:0002371 (Loss of speech) development
HP:0002333 (Motor deterioration)
Seizures
Behavioral Psychiatric Manifestations Severe HP:0000708 (behavioral disturbance) at age 3-4
HP:0000752 (Hyperactivity)
Temper tantrums
Laboratory Abnormalities - Acetyl CoA:alpha-glucosaminidase N-acetyltransferase deficiency in fibroblasts
Heparan sulfate excretion in urine
Metachromasia of white blood cells and fibroblasts
Enzyme replacement therapy has not been effective
Miscellaneous - HP:0003828 (Variable severity)
Most patients appear unaffected in the first year of life
Intellectual regression and HP:0002371 (Loss of speech) precede the onset of HP:0001270 (Delayed motor development) by more than 10 years
Mean age of death is 34 years
Four clinically indistinguishable biochemically distinct forms
Heparan sulfate (U)
HIBCH 610690 3-HYDROXYISOBUTYRYL-CoA HYDROLASE DEFICIENCY; HIBCHD #250620   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0002599 (Head titubation)s
Face
HP:0001999 (Dysmorphic facial features) (in some patients)
Eyes
HP:0000639 (Nystagmus)
HP:0000486 (Strabismus)
HP:0000286 (Epicanthus)
Cardiovascular Heart HP:0001636 (Tetralogy of Fallot)
Abdomen Gastrointestinal HP:0011968 (feeding difficulties)
Persistent HP:0002013 (Vomiting)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Secondarily decreased activities of mitochondrial respiratory enzymes (in some patients)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
HP:0002376 (Psychomotor regression)
Seizures
HP:0001336 (myoclonus)
HP:0007325 (generalized dystonia)
HP:0001251 (ataxia)
HP:0001310 (Dysmetria)
HP:0100022 (Movement disorder)
T2-weighted hyperintensities in the basal ganglia consistent with Leigh syndrome
Laboratory Abnormalities -
Increased lactate
Increased hydroxy-C4-carnitine
Urinary excretion of cysteine and cysteamine conjugates of methacrylic acid
Miscellaneous -
HP:0003593 (Onset in infancy)
Variable features
Increased hydroxy-C4-carnitine
Cysteine and cysteamine conjugates of methacrylic acid (U)
HLCS 609018 HOLOCARBOXYLASE SYNTHETASE DEFICIENCY #253270   2 Inheritance - HP:0000007 (Autosomal recessive)
Respiratory - HP:0002789 (Tachypnea)
HP:0002883 (Hyperventilation)
Abdomen Gastrointestinal HP:0011968 (feeding difficulties)
HP:0002013 (Vomiting)
Skin, Nails, Hair Skin Skin HP:0000988 (rash)
Hair HP:0001596 (Alopecia)
Neurologic Central Nervous SystemHP:0000737 (Irritability)
HP:0008947 (Hypotonia, early)
Seizures
HP:0001254 (Lethargy)
HP:0012758 (neurodevelopmental delay)
Coma
HP:0001276 (Muscle hypertonia)
Metabolic Features - HP:0001942 (metabolic acidosis)
Organic aciduria
Hematology - HP:0001873 (thrombocytopenia)
Laboratory Abnormalities - Organic aciduria (elevated beta-hydroxyisovalerate, beta-methylcrotonylglycine, beta-hydroxypropionate, methylcitrate, lactate, tiglylglycine)
Mild-moderate HP:0001987 (hyperammonemia)
Holocarboxylase synthetase deficiency
Normal serum biotin concentration
Miscellaneous - Age of onset - birth to 15 months
Increased beta-hydroxyisovalerate, beta-methylcrotonylglycine, beta-hydroxypropionate, methylcitrate, lactate, tiglylglycine (U)
Normal serum biotin concentration
HMBS 609806 PORPHYRIA, ACUTE INTERMITTENT; AIP 176000   2 Inheritance - HP:0000006 (Autosomal dominant)
Cardiovascular Heart HP:0001649 (Tachycardia)
Vascular HP:0000822 (Hypertension)
Respiratory Lung HP:0002203 (Respiratory paralysis)
Abdomen Gastrointestinal HP:0002018 (Nausea)
HP:0002013 (Vomiting)
HP:0002014 (Diarrhea)
HP:0002027 (Abdominal pain)
HP:0002019 (Constipation)
Paralytic ileus
Genitourinary Bladder HP:0000016 (Urinary retention)
Dysuria
HP:0000020 (Urinary incontinence)
Neurologic Central Nervous System Acute episodes of neuropathic symptoms
Paraesthesias
Seizures
HP:0000725 (Psychotic episodes)
HP:0000716 (Depression)
HP:0000739 (Anxiety)
Peripheral Nervous System Acute episodes of neuropathic symptoms
Paralysis
Motor, sensory, or autonomic neuropathy
HP:0003324 (Muscle weakness)
Endocrine Features - Syndrome of inappropriate antidiuretic hormone (SIADH)
Neoplasia - Increased incidence of hepatocellular carcinoma
Laboratory Abnormalities - Erythrocyte porphobilinogen (PBG) deaminase deficiency (exception: type II AIP)
Increased urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) during acute attacks
Urine occasionally port-wine in color secondary to porphobilinogen
Miscellaneous - Acute attacks rarely occur before puberty
Attacks precipitated by drugs (e.g. barbiturates, sulfonamides), alcohol, infection, starvation, and hormonal changes
Attacks more common in women
Ninety percent of patients with PBG deaminase deficiency are clinically unaffected
Increased delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) during acute attacks (U)
HMGCL 613898 3-HYDROXY-3-METHYLGLUTARYL-CoA LYASE DEFICIENCY; HMGCLD 246450   3 Neuro Malaise
HP:0001262 (Somnolence)
Coma
Inheritance HP:0000007 (Autosomal recessive)
Metabolic HP:0001942 (Metabolic acidosis)
HP:0001943 (Hypoglycemia)
Sensitivity to dietary leucine
Carnitine deficiency
Misc HP:0001945 (Fever)
Early death
Lab Organic aciduria
3-Hydroxy-3-Methylglutaryl CoA lyase deficiency
Hyperammonemia
High SGOT
3-hydroxy-3-methylglutaric aciduria
3-methylglutaconic aciduria
3-methylglutaric aciduria
3-hydroxyisovaleric aciduria
3-methylglutarylcarnitinuria
No HP:0002919 (Ketonuria)
GI HP:0002240 (Hepatomegaly)
Hypoketotic hypoglycemia
HMGCS2 600234 3-HYDROXY-3-METHYLGLUTARYL-CoA SYNTHASE-2 DEFICIENCY; HMGCS2D 605911   2 0 Hypoketotic hypoglycemia
HNF1B 189907 DIABETES MELLITUS, NONINSULIN-DEPENDENT; NIDDM 125853 26160100 2    
HNRNPR 607201 Epilepsy   26795593 2 0  
HNRNPU 602869 Epilepsy, 1q44 deletion   23494950 2 0  
HRAS 190020 SCHIMMELPENNING-FEUERSTEIN-MIMS SYNDROME; SFM 163200   4 Inheritance - HP:0001442 (Somatic mosaicism)
Growth Height HP:0004322 (short stature)
Other HP:0008897 (Postnatal growth retardation)
Asymmetric HP:0001548 (overgrowth)
Head and Neck Head HP:0002678 (Skull asymmetry)
Eyes Lid lipodermoid
HP:0000589 (coloboma) of HP:0000612; HP:0000636; HP:0000611; eyelids, iris, and choroid
HP:0000544 (Ophthalmoplegia) (in some)
HP:0007957 (corneal opacity) (in some)
Teeth Pigmented, HP:0006482 (malformed teeth)
Cardiovascular Vascular HP:0001680 (Coarctation of aorta)
Genitourinary Kidneys HP:0000085 (Horseshoe kidney)
Skeletal - HP:0000938 (Osteopenia)
HP:0002757 (Recurrent fractures)
Bone deformities
Spine HP:0002751 (kyphoscoliosis)
Hands Finger abnormalities
Feet Toe abnormalities
Skin, Nails, Hair Skin Linear HP:0010815 (nevus sebaceous), often in midfacial area
Lesions follow the lines of Blaschko
HP:0008064 (ichthyosis) hystrix
Nevus unius lateris
HP:0001028 (Hemangioma)
HP:0007513 (Generalized hypopigmentation)
Hair HP:0001596 (Alopecia) within lesion
Neurologic Central Nervous System Neurologic abnormalities in about 7%
HP:0001249 (Intellectual disability)
Seizures
HP:0007206 (Hemimegalencephaly)
Endocrine Features - Hypophosphatemic vitamin D-resistant HP:0002748 (Rickets) (in some)
HP:0000826 (Precocious puberty) (less common)
Neoplasia - Basal cell carcinoma
Syringocystadenoma papilliferum
Central giant cell granuloma
Trichoblastoma
Laboratory Abnormalities - HP:0003109 (Hyperphosphaturia) (in some)
HP:0003109 (Hyperphosphaturia) may disappear after a long period of time
Miscellaneous - Onset of skin lesions at birth
Extracutaneous manifestations are variable
Secondary tumors develop within the skin lesions
 
HSD17B10 300256 17-BETA-HYDROXYSTEROID DEHYDROGENASE X DEFICIENCY #300438   2 Inheritance - HP:0001423 (X-linked dominant)
Head and Neck Ears HP:0000407 (sensorineural hearing loss)
Eyes HP:0000546 (Retinal degeneration)
HP:0000639 (Nystagmus)
Cardiovascular Heart HP:0001639 (hypertrophic cardiomyopathy)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
Progressive HP:0002180 (Neurodegeneration)
HP:0008947 (Hypotonia, early)
HP:0001266 (Choreoathetosis)
Seizures
HP:0002376 (Psychomotor regression)
HP:0000750 (Speech delay)
HP:0001249 (Intellectual disability)
HP:0006892 (Frontotemporal atrophy), mild, seen on MRI
Behavioral Psychiatric Manifestations HP:0000711 (Restlessness)
Metabolic Features - HP:0003128 (Lactic acidosis) (in some patients)
HP:0001942 (metabolic acidosis) (in some patients)
HP:0001943 (Hypoglycemia)
Laboratory Abnormalities - Patient cells show HP:0012103 (Abnormality of the mitochondrion)l morphology
Decreased activity of 2-methyl-3-hydroxybutyryl Co-A dehydrogenase
Increased urinary 2-methyl-3 hydroxybutyrate
Increased urinary tiglylglycine
Miscellaneous - Age at onset can range from infancy to childhood
HP:0003812 (Variable phenotype) and severity
Less severe phenotype in females
Severity of phenotype is not related to residual enzyme activity
Increased 2-methyl-3 hydroxybutyrate (U)
Increased tiglylglycine (U)
HSD17B4 601860 D-BIFUNCTIONAL PROTEIN DEFICIENCY #261515   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive) (44% of patients)
Head and Neck Head HP:0000256 (Macrocephaly)
HP:0000268 (Scaphocephaly)
HP:0000239 (Large fontanels)
HP:0000270 (Delayed closure of fontanel)les
Face HP:0001999 (Dysmorphic features) (68%)
HP:0002007 (Frontal bossing)
HP:0000348 (High forehead)
HP:0000347 (Micrognathia)
HP:0000278 (Retrognathia)
HP:0000343 (Long philtrum)
Ears HP:0000369 (Low-set ears)
Loss of hearing (45%)
Eyes HP:0000582 (Upslanting palpebral fissures)
HP:0000286 (Epicanthus)
HP:0000316 (Hypertelorism)
HP:0000505 (Visual impairment) (55%)
HP:0000639 (Nystagmus)
HP:0000486 (Strabismus)
Failure to fixate on objects
HP:0000572 (Visual loss) (34%)
Abolished electroretinogram (ERG) (76%)
Nose HP:0005280 (depressed nasal bridge)
Mouth HP:0000218 (High-arched palate)
Chest External Features HP:0000767 (Funnel chest)
Long, small thorax
Abdomen Liver HP:0002910 (abnormal liver enzymes) (26%)
HP:0002240 (Hepatomegaly) (43%)
Histology shows normal numbers of peroxisomes (84%)
Abnormal peroxisomes (53%)
Absence of peroxisomes (16%)
HP:0001396 (Cholestasis) (9%)
HP:0001397 (Liver steatosis) (22%)
Fibrosis (22%)
Hemosiderosis (13%)
Proliferation of bile canaliculi (9%)
Gastrointestinal HP:0011968 (feeding difficulties)
Genitourinary Kidneys HP:0000107 (Renal cysts) (33%)
Adrenal cortex atrophy (42%)
Skeletal - Generalized HP:0000938 (Osteopenia)
HP:0002750 (Delayed bone age)
HP:0002832 (Calcific stippling)
Hands HP:0001171 (Claw hands)
Feet HP:0001762 ( Pes equinovarus)
HP:0001765 (Hammertoes)
Muscle, Soft Tissue - HP:0003199 (Decreased muscle mass)
Neurologic Central Nervous System HP:0008947 (Hypotonia, early), neonatal (> 90%)
Seizures (> 90%)
HP:0001263 (Delayed psychomotor development), severe (> 90%)
HP:0002126 (Polymicrogyria) (64%)
HP:0002119 (Ventriculomegaly) (29%)
White matter HP:0007266 (Dysmyelination)/HP:0007305 (CNS demyelination) (71%)
NeoHP:0002539 (Cortical dysplasia) (27%)
Hypoplastic/atrophic corpus callosum (55%)
Heterotopic neurons in the white matter (36%)
Generalized cerebral hypoplasia/atrophy (45%)
HP:0001321 (Cerebellar hypoplasia)/atrophy (27%)
HP:0002171 (Gliosis) (27%)
Peripheral Nervous System Delayed peripheral nerve motor conduction velocities (67%)
Endocrine Features - Adrenocortical insufficiency (uncommon)
Prenatal Manifestations Amniotic Fluid HP:0001561 (Polyhydramnios)
Fetal HP:0001541 (Ascites)
Laboratory Abnormalities - Increased plasma levels of very long-chain fatty acids (VLCFA)
Increased plasma levels of bile acid intermediates
Decreased peroxisomal fatty acid beta-oxidation
Decreased or absent D-bifunctional protein activity and protein
Normal serum plasmalogen
Miscellaneous - HP:0003593 (Onset in infancy)
Early death, usually before age 2 years
Prevalence of 1 in 100,000
Increased very long-chain fatty acids (P)
Increased bile acid intermediates (P)
Normal serum plasmalogen
HSD3B7   BILE ACID SYNTHESIS DEFECT, CONGENITAL, 1; CBAS1     3 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001508 (Failure to thrive)
Abdomen External Features Intrahepatic HP:0001396 (Cholestasis)
HP:0000952 (Jaundice)
HP:0002240 (Hepatomegaly)
Giant cell HP:0012115 (Hepatitis) shown on biopsy
Nonspecific inflammation shown on biopsy
Fibrosis shown on biopsy
HP:0001394 (liver cirrhosis)
Progressive HP:0001399 (Liver failure)
Spleen HP:0001744 (Splenomegaly)
Gastrointestinal HP:0002014 (Diarrhea)
Steatorrhea
Discolored, acholic stools
HP:0002024 (Malabsorption) of fat and fat-soluble vitamins
Skin, Nails, Hair Skin HP:0000952 (Jaundice)
Hematology - HP:0003256 (Coagulopathy) secondary to liver disease
Laboratory Abnormalities - Increased serum bilirubin
HP:0002910 (HP:0002910 (abnormal liver enzymes) tests)
Decreased serum cholesterol
Normal serum levels of gamma-GGT (231950)
Increased serum bilirubin
Abnormal liver function tests
Decreased serum cholesterol
HSPD1 118190 LEUKODYSTROPHY, HYPOMYELINATING, 4; HLD4 612233   5 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly), acquired
Eyes HP:0000639 (Nystagmus)
HP:0000486 (Strabismus)
Respiratory - HP:0002104 (Apneic episodes)
Shallow breathing
Abdomen Gastrointestinal HP:0011968 (feeding difficulties)
Skeletal - Joint HP:0004576 (large joint contractures)
Neurologic Central Nervous System HP:0008947 (Hypotonia, early)
HP:0001263 (global developmental delay)
HP:0001249 (Intellectual disability), profound
No head control
Seizures
HP:0001257 (Spasticity), progressive
HP:0001347 (Hyperreflexia)
HP:0003487 (Extensor plantar responses)
HP:0001266 (Choreoathetosis)
MRI shows no normal myelination
HP:0002415 (Leukodystrophy), hypomyelinating
Laboratory Abnormalities - Intermittent increase of urinary ethylmalonic acid
Serum lactate may be increased during encephalopathic exacerbations
Miscellaneous - Onset between birth and 3 months of age
Usually fatal in first 2 decades
Exacerbation during febrile episodes
Allelic disorder to HP:0000006 (Autosomal dominant) SPG13 (605280)
 
HTR2C 312861 Epilepsy   26795593 2 0  
HTT 613004 HUNTINGTON DISEASE; HD 143100 27329733 4 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Face Oral motor dysfunction (juvenile form)
Eyes Shallow breathingt
Neurologic Central Nervous System HP:0001347 (Hyperreflexia)
HP:0002072 (Chorea)
HP:0000726 (Dementia)
HP:0002067 (Bradykinesia)
HP:0000496 (oculomotor abnormalities)
Seizures (juvenile form)
HP:0002063 (Rigidity) (juvenile form)
HP:0001251 (ataxia)(juvenile form)
HP:0002529 (Neuronal loss) and HP:0002171 (Gliosis) in caudate and putamen
HP:0001272 (Cerebellar atrophy) (juvenile form)
Behavioral Psychiatric Manifestations HP:0000716 (Depression)
HP:0000751 (Personality change)
Miscellaneous - Onset first to seventh decade with 30 to 40 year mode
Prevalence much higher in whites than blacks
Juvenile rigid early-onset form more often paternally inherited
Normal range of expanded repeats 9-29, HD range 36-121
Complete penetrance
 
IBA57 615316 MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 3; MMDS3 #615330   2 Inheritance - HP:0000007 (Autosomal recessive)
Growth Other HP:0001511 (Intrauterine growth retardation)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0000278 (Retrognathia)
Mouth HP:0000218 (High-arched palate)
Chest Breasts HP:0006610 (Widely spaced nipples)
Skeletal - HP:0002804 (Arthrogryposis)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early), severe
Defects in mitochondria respiratory activities, mainly complexes I, II, and IV
Defects in lipoate-containing mitochondrial enzyme complexes
Neurologic Central Nervous System HP:0004319 (nonprogressive encephalopathy)
HP:0008947 (Hypotonia, early), severe
Absent primitive reflexes
HP:0002283 (global brain atrophy)
HP:0002126 (Polymicrogyria)
HP:0002079 (Hypoplasia of the corpus callosum)
Hypoplasia of the medulla oblongata
Cortical cytotoxic HP:0000969 (Edema)
HP:0002500 (White matter abnormalities)
Metabolic Features - HP:0003128 (Lactic acidosis)
HP:0001942 (metabolic acidosis)
Prenatal Manifestations Amniotic Fluid HP:0001561 (Polyhydramnios)
Laboratory Abnormalities - HP:0002151; HP:0002490 (Increased serum and CSF lactate)
Increased serum and CSF glycine
Miscellaneous - HP:0003577 (prenatal onset)
Death in the perinatal period
Increased lactate (P, C)
Increased glycine (P, C)
IDH2 147650 D-2-HYDROXYGLUTARIC ACIDURIA 2; D2HGA2 #613657   2 0 D-2-hydroxyglutaric aciduria
IDS 300823 MUCOPOLYSACCHARIDOSIS, TYPE II; MPS2 #309900   2 Inheritance - HP:0001419 (X-linked recessive)
Growth Height HP:0003510 (short stature), mild
Adult height 120-150cm
Head and Neck Head HP:0000268 (Scaphocephaly)
HP:0000256 (Macrocephaly)
Face HP:0000280 (Coarse facies)
EarsHP:0000410 (Hearing loss, mixed)
Recurrent HP:0000388 (Otitis media)
Eyes No HP:0007957 (Corneal opacity)
HP:0001085 (Papilledema)
Retinal pigmentation
HP:0000508 (Ptosis)
Nose Mucoid nasal discharge
Mouth HP:0000158 (Macroglossia)
HP:0012471 (full lips)
Teeth Delayed tooth eruption
HP:0000687 (Widely spaced teeth)
Neck HP:0000470 (Short neck)
Cardiovascular Heart HP:0001654 (Valvular heart disease)
Ischemic heart disease
HP:0001635 (Congestive heart failure)
Respiratory Airways Tracheobronchomalacia
Obstructive HP:0010535 (sleep apnea)
Asthma
Abdomen External Features HP:0000023 (Inguinal hernia)
HP:0001537 (Umbilical hernia)
Liver HP:0002240 (Hepatomegaly)
Spleen HP:0001744 (Splenomegaly)
Gastrointestinal HP:0002014 (Diarrhea)
Intestinal pseudo-obstruction
Skeletal - HP:0000943 (dysostosis multiplex)
Spine HP:0002808 (Kyphosis)
Limbs Flexion HP:0004576 (large joint contractures)
Hands HP:0001171 (Claw hand)
Feet HP:0001761 (Pes cavus)
Skin, Nails, Hair Skin Pebbly skin lesions on back, upper arms, and thigh
Hair HP:0000998 (hypertrichosis)
Neurologic Central Nervous System HP:0002180 (Neurodegeneration) leading to profound HP:0001249 (Intellectual disability)
Cervical cord compression
HP:0000238 (Hydrocephalus)
Normal intelligence in IIB
Seizures
Voice - HP:0001609 (Hoarse voice)
Laboratory Abnormalities - Iduronate sulfatase deficiency in fibroblasts, amniocytes and white blood cells
Dermatan and heparan sulfate excretion in urine
Miscellaneous - Onset 2-4 years of age in IIA
Two forms: IIA (severe) and IIB (mild)
Death before age 15 in IIA
Survival to 20s-60s in IIB
Prenatal diagnosis available
Dermatan and heparan sulfate (U)
IER3IP1 609382 MICROCEPHALY, EPILEPSY, AND DIABETES SYNDROME; MEDS #614231   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly) (about 3 SD below the mean)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay), severe
HP:0008947 (Hypotonia, early)
Seizures
HP:0002123 (Myoclonic seizures)
HP:0002521 (hypsarrhythmia)
HP:0009879 (Simplified gyral pattern)
HP:0002079 (Thin corpus callosum)
HP:0012448 (Delayed myelination)
ApoHP:0000508 (Ptosis) of neurons
Endocrine Features - HP:0000819 (Diabetes mellitus), infantile
Few and small islets of Langerhans
HP:0000815 (Hypogonadism)
Death before age 3 years
 
IFIH1 606951 AICARDI-GOUTIERES SYNDROME 7; AGS7 615846   2 Inheritance - HP:0000006 (Autosomal dominant)
Growth Other HP:0001511 (Intrauterine growth retardation) (IUGR)
Head and Neck Head HP:0000252 (microcephaly) (in some patients)
Eyes HP:0000496 (oculomotor abnormalities) (in some patients)
Abdomen Liver HP:0002240 (Hepatomegaly) (in some patients)
Spleen HP:0001744 (Splenomegaly) (in some patients)
Gastrointestinal HP:0011968 (feeding difficulties)
Genitourinary Kidneys HP:0000100 (Nephrotic syndrome)
Skin, Nails, Hair Skin HP:0002633 (Vasculitis)
Atopic HP:0011123 (dermatitis)
Lack of chilblain lesions
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
HP:0000737 (Irritability), neonatal
HP:0001249 (Intellectual disability)
HP:0001344 (absent speech)
HP:0002376 (Psychomotor regress)(in some patients)
Axial HP:0008947 (Hypotonia, early), severe
Spastic HP:0002273 (Quadriplegia)
HP:0007325 (generalized dystonia)
Seizures (in some patients)
HP:0002135 (Basal ganglia calcification)
HP:0002283 (global brain atrophy)
T2-weighted signal abnormalities in the deep white matter
Hematology - HP:0001873 (thrombocytopenia) (in some patients)
Immunology - Lupus-like syndrome (in some patients)
Hyperinflammatory state
Increased alpha-interferon activity
Upregulation of alpha-interferon-stimulated genes
Autoantibodies (in some patients)
Hypergammaglobulinemia (in some patients)
Hypocomplementemia (in some patients)
Miscellaneous - HP:0003593 (Onset in infancy) or early childhood
HP:0003828 (Variable severity)
HP:0003829 (Incomplete penetrance)
 
IKBKG 300248 INCONTINENTIA PIGMENTI; IP 308300   2 Inheritance - HP:0001423 (X-linked dominant)
Growth Height HP:0004322 (short stature)
Head and Neck Head HP:0000252 (microcephaly)
Eyes HP:0000568 (Microphthalmia)
HP:0000518 (Cataracts)
HP:0000648 (optic atrophy)
HP:0000486 (Strabismus)
Retinal vascular proliferation
Retinal ischemia
Retinal bleeding
Retinal fibrosis
HP:0000541 (Retinal detachment)
HP:0000554 (Uveitis)
HP:0000491 (keratitis)
Teeth HP:0000668 (Hypodontia)
Delayed eruption
Conical forms
Accessory cusps
Chest Ribs, Sternum, Clavicles and Scapulae HP:0005815 (Supernumerary ribs)
Breasts HP:0002558 (Supernumerary nipple)
HP:0002557 (Nipple hypoplasia)
HP:0010311 (HP:0003187 (Breast hypoplasia)/aplasia)
Skeletal Spine HP:0002937 (Hemivertebrae)
HP:0002751 (kyphoscoliosis)
Skin, Nails, Hair Skin STAGE 1 - skin erythema, vesicles, pustules
Onset birth-newborn period
Affects limbs and trunk
Occurs in linear distribution
STAGE 2 - Skin HP:0200034 (Papules), verrucous lesions, HP:0007543 (epidermal hyperkeratosis)
Affects distal limb and scalp
STAGE 3 - Skin HP:0000953 (hyperpigmentation)
Primarily affects trunk
Follows Blaschko's lines
Streaks and whorls
Fades in adolescence
STAGE 4 - skin pallor, atrophy, and scarring
Most evident on lower legs
Nails Nail dystrophy
Nail ridging
Nail pitting
HP:0001805 (Onychogryposis)
Subungual keratotic tumors
Hair Atrophic, patchy HP:0001596 (Alopecia) (vertex)
Wiry, HP:0002208 (Coarse hair) (childhood)
Thin, HP:0008070 (Sparse hair) (childhood)
Neurologic Central Nervous System Seizures
HP:0001249 (Intellectual disability)
HP:0001257 (Spasticity)
Hematology - HP:0001974 (Leukocytosis) with eosinophilia during stage 1
 
IL1RAPL1 300206 MENTAL RETARDATION, X-LINKED 21; MRX21 300143   4 Inheritance - HP:0001419 (X-linked recessive)
Head and Neck Face Mild HP:0001999 (Dysmorphic features)
Hypotonic midface
HP:0000303 (Prominent jaw)
Ears HP:0009894 (Thick ears)
Upturned lobes
Eyes HP:0000316 (Hypertelorism)
HP:0000582 (Upslanting palpebral fissures)
HP:0000664 (Synophrys)
Nose HP:0003196 (Short nose)
Thickened alae nasi and columella
Mouth HP:0000194 (Open mouth)
HP:0010804 (Tented upper lip)
Teeth HP:0000678 (crowded teeth)
Skeletal - HP:0001382 (Hyperextensible joints)
Neurologic Central Nervous System HP:0001249 (Intellectual disability), moderate
Seizures (1 family)
Behavioral Psychiatric Manifestations HP:0000729 (autistic behaviour)
HP:0000752 (Hyperactivity)
Miscellaneous - Carrier females may have mild features
 
INS 176730 DIABETES MELLITUS, PERMANENT NEONATAL; PNDM 606176   2 Inheritance - HP:0000006 (Autosomal dominant)
Growth Weight HP:0001518 (Small for gestational age)
Other HP:0001511 (Intrauterine growth retardation)
Postnatal growth catch-up occurs in treated patients without neurologic abnormalities
Head and Neck Head HP:0005487 (Metopic ridging)
Face HP:0000343 (Long philtrum)
Ears HP:0009894 (Thick ears)
Eyes HP:0000508 (Ptosis)
Nose Small, HP:0003196 (Short nose)
HP:0000463 (Anteverted nostrils)
Mouth HP:0002714 (Downturned mouth)
Abdomen Pancreas HP:0006279 (Beta-cell dysfunction)
Skeletal - Limb HP:0004576 (large joint contractures)
Hands HP:0004209 (Fifth finger clinodactyly)
Muscle, Soft Tissue - HP:0003324 (Muscle weakness)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
HP:0001270 (Delayed motor development)
Axial HP:0008947 (Hypotonia, early)
Diffuse HP:0008947 (Hypotonia, early)
Seizures
HP:0002521 (hypsarrhythmia)
EEG shows epileptiform activity
Peripheral Nervous System Diabetic HP:0009830 (Peripheral neuropathy) in long-standing cases
Endocrine Features - HP:0000819 (Diabetes mellitus)
Immunology - Absence of pancreatic autoantibodies
Laboratory Abnormalities - HP:0003074 (Hyperglycemia)
HP:0001993 (ketoacidosis)
Miscellaneous - Diagnosis within the first 3 months of life
Some patients do not show neurologic abnormalities or HP:0001999 (Dysmorphic features)
Some patients show a favorable response to sulfonylurea treatment
 
INSR 147670 HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 5; HHF5 609968   3 Inheritance - HP:0000006 (Autosomal dominant)
Neurologic Central Nervous System Loss of consciousness due to HP:0001943 (Hypoglycemia)
HP:0002173 (Hypoglycemic seizures)
Endocrine Features - Hyperinsulinemic HP:0001943 (Hypoglycemia)
Laboratory Abnormalities - HP:0001943 (Hypoglycemia), postprandial
HP:0000842 (Hyperinsulinemia), fasting
Elevated serum insulin-to-C-peptide ratio
Miscellaneous - Genetic heterogeneity (see HHF1 256450)
Hypoglycemia, postprandial
Hyperinsulinemia, fasting
Elevated serum insulin-to-C-peptide ratio
IQSEC2 300522 MENTAL RETARDATION, X-LINKED 1; MRX1 #309530   2 Neuro HP:0001249 (Intellectual disability)
Inheritance X-linked, nonspecific type
multiple loci
 
ISPD 614631 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 7; MDDGA7 #614643   4 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000256 (Macrocephaly)
HP:0002007 (Frontal bossing)
Face HP:0000278 (Retrognathia)
Ears HP:0008551 (Small ears)
HP:0000369 (Low-set ears)
Eyes HP:0000490 (Deep-set eyes)
HP:0000568 (Microphthalmia)
HP:0000518 (Cataracts)
Persistent hyperplastic primary vitreous
Arrested retinal development
HP:0000541 (Retinal detachment)
HP:0007973 (Retinal dysplasia)
HP:0000609 (Optic nerve hypoplasia)
HP:0000659 (Peters anomaly)
HP:0000501 (Glaucoma)
Abdomen - Visceral malformations (in some patients)
Skeletal Limbs Limb deformations (in some patients)
Hands HP:0001181 (Adducted thumbs)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early)
HP:0003560 (Muscular dystrophy)
Disruption in the basal lamina seen on skeletal muscle biopsy
Defect in glycosylation of alpha-dystroglycan seen on skeletal muscle biopsy
Neurologic Central Nervous System HP:0008947 (Hypotonia, early)
HP:0001249 (Intellectual disability), profound
HP:0000238 (Hydrocephalus)
HP:0002119 (ventriculomegaly)
HP:0002084 (Encephalocele)
HP:0001305 (Dandy-Walker malformation)
Cobblestone HP:0001339 (Lissencephaly)
HP:0001339 (Agyria)
HP:0001302 (pachygyria)
HP:0002126 (Polymicrogyria)
HP:0002079 (Hypoplasia of the corpus callosum)
Partial HP:0001274 (agenesis of corpus callosum)
Cortical thinning
Subcortical HP:0002282 (heterotopia)
HP:0001321 (Cerebellar hypoplasia)
HP:0002365 (Brainstem hypoplasia)
Brain vascular anomalies (rare)
Peripheral Nervous System HP:0001284 (Areflexia)
Prenatal Manifestations Movement HP:0001558 (Decreased fetal movement)
Laboratory Abnormalities - HP:0003236 (Increased serum creatine kinase)
Miscellaneous - Onset prenatally or at birth
Severe phenotype
Most patients die in first years of life
Increased serum creatine kinase
ITPA 147520 EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 35; EIEE35 616647   1 Inheritance -
HP:0000007 (Autosomal recessive)
Growth Other
HP:0001511 (Intrauterine growth retardation)
HP:0001510 (growth delay)
Head and Neck Head
HP:0000252 (microcephaly) (up to -6 SD)
Eyes
HP:0000518 (Cataracts) (1 family)
Minimal eye contact
Cardiovascular Heart
HP:0001638 (Cardiomyopathy)
Electrocardiogram abnormalities (in some patients)
Abdomen Gastrointestinal
HP:0011968 (feeding difficulties)
Muscle, Soft Tissue -
HP:0008947 (Hypotonia, early), severe
Neurologic Central Nervous System
HP:0004319 (nonprogressive encephalopathy)
HP:0001263 (Lack of psychomotor development)
Seizures
HP:0002283 (global brain atrophy)
HP:0012448 (Delayed myelination)
Abnormal T2-weighted signals and diffusion restriction in the posterior limb of the internal capsule
Abnormal T2-weighted signals in the optic radiations
Abnormal T2-weighted signals in the midbrain brainstem tracts
Abnormal T2-weighted signals in the cerebellar white matter
Miscellaneous -
Onset soon after birth
HP:0001522 (Death in early childhood) may occur
 
IVD 607036 ISOVALERIC ACIDEMIA; IVA #243500   2 Inheritance - HP:0000007 (Autosomal recessive)
Abdomen Gastrointestinal Feeding refusal, especially aversion to protein
HP:0002013 (Vomiting)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay)
HP:0001254 (Lethargy)
Seizures
Coma
HP:0011695 (Cerebellar hemorrhage) (rare)
Metabolic Features - HP:0001942 (metabolic acidosis)
HP:0001993 (ketoacidosis)
HP:0001944 (Dehydration)
Hematology - HP:0001873 (thrombocytopenia)
HP:0001882 (Leukopenia)
HP:0001876 (Pancytopenia)
HP:0005528 (Hypoplastic bone marrow)
Laboratory Abnormalities - Isovalericacidemia
Isovalericaciduria
Isovalerylglycinuria
Deficiency of mitochondrial isovaleryl-CoA dehydrogenase in fibroblasts
Miscellaneous - Approximately 50% of cases are acute, severe neonatal illness often with rapid death and 50% are chronic episodic with asymptomatic intervals
Odor of 'sweaty feet'
Isovalericacidemia
Isovalericaciduria
Isovalerylglycinuria
JAM3 606871 HEMORRHAGIC DESTRUCTION OF THE BRAIN, SUBEPENDYMAL CALCIFICATION, AND CATARACTS; HDBSCC 613730   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly), postnatal
Eyes HP:0000518 (Cataracts), congenital
Abdomen Liver HP:0002240 (Hepatomegaly)
Genitourinary Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
Kidneys HP:0000110 (renal dysplasia) (in some)
HP:0000086 (Renal ectopia)
Renal cystic dysplasia
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay), profound
Intraparenchymal brain hemorrhage, multifocal
Cystic destruction of brain tissue, including basal ganglia
HP:0002119 (ventriculomegaly)
HP:0002132 (Porencephaly)
Subependymal calcifications
Reduced white matter volume
Seizures
HP:0001257 (Spasticity)
HP:0001347 (Hyperreflexia)
Atrophic pons (in some)
HP:0001321 (Cerebellar hypoplasia) (in some)
Miscellaneous - HP:0003577 (Onset at birth)
Death usually occurs in early infancy
Resembles pseudo-TORCH syndrome (251290)
 
KANSL1 612452 KOOLEN-DE VRIES SYNDROME; KDVS #610443   2 Inheritance - HP:0000006 (Autosomal dominant)
Growth Weight HP:0001511 (Intrauterine growth retardation)
HP:0001518 (Small for gestational age) (27%)
HP:0001508 (Failure to thrive)
Head and Neck Face HP:0000276 (Long face) (74%)
High, HP:0000337 (Broad forehead) (68%)
Broad chin (42%)
Ears HP:0000400 (macrotia) (59%)
Anteverted ears
HP:0000396 (Overfolded helices)
Eyes HP:0000540 (Hypermetropia) (36%)
Pale irides (45%)
HP:0000486 (Strabismus) (45%)
HP:0000582 (Upslanting palpebral fissures) (68%)
HP:0000581 (Blepharophimosis) (36%)
HP:0000508 (Ptosis) (50%)
HP:0000286 (Epicanthus) (68%)
Nose Tubular nose (82%)
Pear-shaped nose (82%)
HP:0000414 (Bulbous nasal tip) (95%)
HP:0000426 (High nasal bridge)
Mouth High, HP:0000189 (Narrow palate) (50%)
HP:0100333 (Unilateral cleft lip)
HP:0000175 (Cleft palate)
HP:0000179 (Thick lower lip vermilion)
HP:0000194 (Open mouth)
Teeth Small HP:0000687 (Widely spaced teeth)
Cardiovascular Heart HP:0002564 (Congenital heart defect)s (27%)
HP:0001631 (Atrial septal defect)
HP:0001629 (Ventricular septal defect)
HP:0001642 (Pulmonary valve stenosis)
HP:0001647 (Bicuspid aortic valve)
HP:0001724 (Aortic dilatation)
Chest External Features HP:0000767 (HP:0000766 (Pectus deformities) excavatum) (23%)
HP:0006610 (Widely spaced nipples)
Genitourinary - Kidney/urologic anomalies (32%)
Kidneys HP:0000126 (Hydronephrosis)
Duplex renal system
Bladder
Skeletal - Hypermobile joints
Spine HP:0002650 (Scoliosis)/HP:0002808 (Kyphosis) (36%)
Pelvis HP:0002827 (Hip dislocations) (27%)
Limbs Slender lower limbs (41%)
Hands HP:0004283 (Narrow hands) (28%)
HP:0001166 (Arachnodactyly) (61%)
Hypoplasia of the hand muscles (29%)
Feet Positional foot deformity (27%)
Skin, Nails, Hair Skin HP:0000958 (Dry skin)
HP:0000964 (Eczema)
Pigmentary abnormalities
HP:0000960 (Sacral dimple)
Hair Abnormal hair pigmentation (55%)
Abnormal hair texture (55%)
Muscle, Soft Tissue - Hypoplasia of the hand muscles (29%)
Neurologic Central Nervous System HP:0012758 (neurodevelopmental delay) (100%)
HP:0001249 (Intellectual disability), mild to severe
HP:0000750 (language delay)
HP:0008947 (Hypotonia, early) (96%)
Seizures (50%)
HP:0002119 (ventriculomegaly) (38%)
Behavioral Psychiatric Manifestations Friendly behavior (89%)
Voice - HP:0001611 (Nasal speech) (50%)
Miscellaneous - All cases are de novo
Estimated prevalence of 1 in 16,000
Contiguous gene deletion of 17q21.3 involves a region which harbors a 900kb inversion polymorphism
 
KAT6A 601408 MENTAL RETARDATION, AUTOSOMAL DOMINANT 32; MRD32 616268   4 Inheritance - HP:0000006 (Autosomal dominant)
Growth Other HP:0001510 (growth delay)
Head and Neck Head HP:0000252 (microcephaly)
HP:0001357 (Plagiocephaly)
Face HP:0000341 (Bitemporal narrowing)
MicroHP:0000278 (Retrognathia)
Ears HP:0000369 (Low-set ears)
HP:0000358 (Posteriorly rotated ears)
Eyes HP:0000486 (Strabismus)
HP:0000508 (Ptosis)
HP:0000286 (Epicanthus)
Cortical HP:0000505 (Visual impairment)
Nose HP:0000426 (Prominent nasal root)
HP:0000426 (Prominent nasal bridge)
HP:0000455 (Broad nasal tip)
Mouth HP:0000219 (Thin upper lip)
HP:0002714 (Downturned mouth)
Teeth HP:0006482 (Malformed teeth)
Cardiovascular Heart HP:0001631 (Atrial septal defect)
HP:0001629 (Ventricular septal defect)
HP:0001643 (Patent ductus arteriosus)
Respiratory - HP:0002098 (Respiratory distress), neonatal
Abdomen Gastrointestinal HP:0011968 (feeding difficulties)
Gastrointestinal reflux
Skeletal Skull HP:0011324 (multisutural craniosynostosis)
Muscle, Soft Tissue - HP:0008947 (Hypotonia, early), neonatal
Neurologic Central Nervous System HP:0001263 (Delayed psychomotor development)
Poor or HP:0001344 (absent speech)
Seizures (rare)
Miscellaneous - All reported mutations have occurred de novo
Facial HP:0001999 (Dysmorphic features) are variable
 
KAT6B 605880 GENITOPATELLAR SYNDROME; GTPTS 606170   2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Head HP:0000252 (microcephaly)
Face HP:0000280 (Coarse facies)
HP:0000347 (Micrognathia)
EarsHP:0000410 (Hearing loss, mixed)
Eyes HP:0000494 (Downslanting palpebral fissures)
Nose HP:0000445 (Broad nose)
HP:0000448 (Large nose)
HP:0000426 (High nasal bridge)
Teeth Delayed tooth eruption
Cardiovascular Heart HP:0001631 (Atrial septal defect)
HP:0001629 (Ventricular septal defect)
Respiratory Larynx HP:0001601 (Laryngomalacia)
Lung HP:0004971 (Pulmonary hypoplasia)
Abdomen Gastrointestinal HP:0001545 (Anteriorly placed anus)
HP:0002015 (Swallowing difficulties)
Genitourinary - Hypoplastic perineum
External Genitalia (Male) Hypoplasic scrotum
HP:0000054 (Small penis)
External Genitalia (Female) HP:0008665 (Clitoral hypertrophy)
Labia minora hypertrophy
Internal Genitalia (Male) HP:0000028 (Cryptorchidism)
KidneysHP:0000003 (Multicystic kidney)s
HP:0000126 (Hydronephrosis)
Skeletal Pelvis Hip HP:0004576 (large joint contractures)
Hip flexion deformities
Hypoplastic ischia
Hypoplastic inferior pubic rami
congenital HP:0002827 (Hip dislocations)
Limbs Limb HP:0004576 (large joint contractures)
HP:0006443 (Absent patellae)
Knee flexion deformities
HP:0002974 (Radioulnar synostosis)
Hands HP:0009803 (short fingers)
Feet HP:0001762 ( Pes equinovarus)
Skin, Nails, Hair Skin Dimple overlying knee
Hair HP:0002209 (Sparse scalp hair)
Neurologic Central Nervous System HP:0001274 (Agenesis of corpus callosum)
HP:0001263 (global developmental delay), severe
HP:0008947 (Hypotonia, early)
HP:0030048 (Colpocephaly)
Periventricular neuronal HP:0002282 (heterotopia)
Prenatal Manifestations Amniotic Fluid HP:0001561 (Polyhydramnios)
 
KATNB1 602703 LISSENCEPHALY 6 WITH MICROCEPHALY; LIS6 616212   2 Inheritance - HP:0000007 (Autosomal recessive)
Head and Neck Head HP:0000252 (microcephaly) (up to -6 SD)
Face HP:0000340 (Sloping forehead)
Neurologic Central Nervous System HP:0001263 (global developmental delay)
HP:0100543 (Cognitive impairment)
HP:0001270 (Delayed motor development) (in some patients)
Seizures (in some patients)
HP:0001257 (Spasticity) (in some patients)
Limb HP:0001276 (Muscle hypertonia) (in some patients)
HP:0001347 (Hyperreflexia) (in some patients)
Reduced brain size
HP:0001339 (Lissencephaly)
HP:0009879 (Simplified gyral pattern)
HP:0002079 (Thin corpus callosum)
Partial HP:0001274 (agenesis of corpus callosum)
Undersulcation of the frontal lobes
HP:0001302 (pachygyria)
HP:0002126 (Polymicrogyria)
Nodular HP:0002282 (heterotopia) of the grey matter
MicroHP:0001339 (Lissencephaly)
HP:0002119 (Ventriculomegaly)
HP:0009879 (Simplified gyral pattern)
Miscellaneous - HP:0003593 (Onset in infancy)
Variable neuroradiologic findings
 
KCNA1 176260 Autosomal dominant hypomagnesemia   19307729 2 Inheritance - HP:0000006 (Autosomal dominant)
Head and Neck Ears HP:0002321 (Vertigo), episodic
Eyes HP:0000622 (Blurred vision), episodic
Skeletal Hands Hand posture resembling carpopedal spasm, episodic
Muscle, Soft Tissue - HP:0008981 (Calf hypertrophy)
EMG shows polyphasic continuous motor unit discharges
Muscle biopsy shows enlargement of type I muscle fibers, consistent with denervation
Neurologic Central Nervous System HP:0002131 (episodic ataxia)
HP:0001260 (Dysarthria)
HP:0001350 (Slurred speech)
Dizziness
HP:0002311 (Incoordination) of the hands
Leg stiffness
HP:0002064 (Spastic gait)
Coarse HP:0002322 (Resting tremor)
Headache
HP:0001347 (Hyperreflexia)
HP:0003487 (Extensor plantar responses) (reported in 1 family)
Peripheral Nervous System HP:0002411 (Myokymia), interictal
Jerking movements of face and limbs
Laboratory Abnormalities - HP:0003236 (Increased serum creatine kinase) during episodes
Miscellaneous - Onset in childhood
Highly HP:0003828 (Variable severity)
Symptoms precipitated by sudden movement, stress, exertion, fatigue, illness
Typical attacks last from seconds to minutes, but longer occurrences have been reported
HP:0011157 (Auras) may occur
Some patients may develop interictal progressive HP:0001251 (ataxia)
Variable response to acetazolamide and carbamazepine
 
KCNA2 176262 EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 32; EIEE32 #616366   1 Inheritance - HP:0000006 (Autosomal dominant)
Neurologic Central Nervous System Normal early development
Epileptic HP:0004319 (nonprogressive encephalopathy)
Seizures, refractory
HP:0001249 (Intellectual disability), mild to profound
Poor or HP:0001344 (absent speech)
HP:0001251 (ataxia)
HP:0001336 (myoclonus)
HP:0002322 (Resting tremor)
Multifocal or generalized spike waves seen on EEG
Sharp slow wave activity
Miscellaneous - HP:0003593 (Onset in infancy)
Normal development before onset of seizures
Seizures may remit later in childhood
 
KCNB1 600397 EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 26; EIEE26 #616056   1 Inheritance - HP:0000006 (Autosomal dominant)
Neurologic Central Nervous System Epileptic HP:0004319 (nonprogressive encephalopathy)
HP:0001263 (Delayed psychomotor development)
Poor or HP:0001344 (absent speech)
Seizures, multiple types
HP:0008947 (Hypotonia, early)
HP:0002521 (hypsarrhythmia)
Multifocal epileptiform spikes seen on EEG
Miscellaneous - HP:0003593 (Onset in infancy)
Seizures are refractory to treatment
 
KCNC1 176258 EPILEPSY, PROGRESSIVE MYOCLONIC 7; EPM7 #616187   2 Inheritance - HP:0000006 (Autosomal dominant)
Neurologic Central Nervous System Normal early development
HP:0002123 (Myoclonic seizures)
HP:0001336 (myoclonus)
HP:0002069 (Tonic-clonic seizures)
HP:0002322 (Resting tremor)
HP:0001251 (ataxia) (in some patients)
HP:0001328 (Learning disabilities) (in some patients)
HP:0001268 (cognitive decline) (in some patients)
HP:0001272 (Cerebellar atrophy) (in some patients)
Miscellaneous - Onset between 6 and 14 years
HP:0003676 (Progressive disorder)
Most mutations occur de novo
Most patients become wheelchair-bound in adolescence
 
KCND2 605410 Autism and seizures   24501278 2 0  
KCNH1 603305 ZIMMERMANN-LABAND SYNDROME 1; ZLS1 135500   2 Inheritance - HP:0000006 (Autosomal dominant)
Growth Weight HP:0001548; Birthweight greater than 90th percentile
Head and Neck Face HP:0000280 (Coarse facies)
HP:0000303 (Mandibular prognathia)
Ears Long, lobulated ears
HP:0000358 (Posteriorly rotated ears)
HP:0008619 (Hearing loss, bilateral sens