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Gene (Age of Onset (Range, Years)/Penetrance (%)/MOI) |
Main Neurological Symptoms | Other Symptoms | Brain Calcification |
---|---|---|---|
SLC20A2 (1–84/60%/AD) |
>20%: Parkinsonism, cognitive deficit, headache 10–20%: Tremor, dysarthria, dystonia <10%: Depression, psychosis, ataxia, anxiety, seizure, chorea |
Basal ganglia, subcortical white matter, and dentate nuclei | |
PDGFB (1–70/86%/AD) |
>20%: Headache, cognitive deficit, depression 10–20%: Parkinsonism, psychosis, ataxia, tremor, chorea, anxiety <10%: Dystonia, dysarthria, seizure |
Basal ganglia, subcortical white matter, and dentate nuclei | |
PDGFBR (6–82/48%/AD) |
>20%: Headache, cognitive deficit 10–20%: Depression, Parkinsonism <10%: Tremor, anxiety, dysarthria, seizure, psychosis, ataxia, tremor, chorea, dystonia |
Basal ganglia, subcortical white matter, and dentate nuclei | |
XPR1 (16–79/70%/AD) |
>20%: Cognitive deficit, Parkinsonism, dysarthria 10–20%: Tremor, ataxia <10%: Headache, anxiety, seizure, psychosis, depression, dystonia, chorea |
Basal ganglia, subcortical white matter, and dentate nuclei | |
MYORG (8–87/91%/AR) |
>20%: Dysarthria, cognitive deficit, ataxia, parkinsonism, psychosis, tremor 10–20%: Depression <10%: Headache, dystonia, chorea, seizure, anxiety |
Basal ganglia, subcortical white matter, and dentate nuclei | |
JAM2 (7–50/85%/AR) |
>20%: Parkinsonism, ataxia, cognitive deficit, dysarthria, seizure <10%: Dystonia |
Basal ganglia, subcortical white matter, and dentate nuclei, midbrain | |
Mitochondrial conditions (MERRF, Leigh syndrome, KSS—mtDNA) (Childhood, adulthood/full/matrilinear) |
Epilepsy, myoclonus, ataxia, spasticity Dysphagia (LS) |
Short stature, optic atrophy, hearing loss, ptosis, diabetes mellitus, cardiomyopathy, neuropathy, myopathy, diarrhea, vomiting (LS), lactic acidosis |
Basal ganglia calcifications |
Coats plus syndrome (CTC1) (Childhood/full/AR) |
Developmental delay, epilepsy, spasticity, dystonia, ataxia | Retinal telangiectasia and exudates, osteopenia and fractures, gastrointestinal and hepatic bleeding, portal hypertension, bone marrow suppression Growth retardation |
Calcification with leukoencephalopathy and brain cysts |
Aicardi-Goutières syndrome (ADAR, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, TREX1, IFIH1) (Childhood (usually after a short period of normal development)/full/AR/AD) |
Dystonia, hypotonia, developmental delay Increased startle reaction |
Acquired microcephaly, Hepatosplenomegaly Sterile pyrexias Chilblain lesions (ears, hands, fee) Skin mottling Increased liver enzyme, thrombocytopenia (transitory), interferon signature |
Calcifications of basal ganglia and white matter Leukoencephalopathy Progressive cerebral atrophy |
Leukoencephalopathy, cystic, without megalencephaly (RNASET2) (1 year/full/AR) |
Seizure Neurological deterioration |
Microcephaly | Brain calcification Cystic lesions (anterior, subcortical) Leukoencephalopathy |
Claudin-5 (CLDN5) (1 year/full/AR) |
Seizure Developmental delay |
Atrophy of the pons Calcification of the vertical pontine white matter bundles Cortical and basal ganglia calcification |
|
Hoyeraal Hreidarsson syndrome (DKC1, TINF2) and Congenital Dyskeratosis (Zinsser-Engman-Cole syndrome) (TERC, TERT, NHP2, NOP10, WRAP53, RTEL1) (Childhood (first months)/full/AR X-linked/AD/AR) |
Neurodevelopmental delay | Microcephaly Persistent pancytopenia Hepatic and pulmonary fibrosis Dyskeratosis (skin pigmentation, leukoplakia, toenail dystrophy) Scoliosis |
Cerebellar hypoplasia Basal ganglia and subcortical calcifications |
3-hydroxyisobutyric aciduria (1st decade/NA/NA) |
Hypotonia and impaired neurological development | Microcephaly Facial dysmorphism Episodes of ketoacidosis |
Migration brain disorder Calcification in the frontal and subependymal region and periventricular |
Inborn error of folates Metabolism (FOLR1, SLC46A1, MTHFR, DHFR, MTFD1) (1st decade/full/AR) |
Seizure Severe neurological deterioration |
Leukopenia, megaloblastic bone marrow, hypoimmunoglobulinemia. | Demyelination Calcification of basal ganglia and white matter |
Carbonic anhydrase II deficiency syndrome (CA2) (Congenital/full/AR) |
Possible mental retardation | Osteopetrosis Renal tubular acidosis |
Calcification of the basal ganglia, thalamus, subcortical white matter |
Collagen IV disorders (COL4A1, COL4A2) (Childhood–adult/full/AD) |
Seizure Ischemic or hemorrhagic events Migraine with aura (also isolated) Severe cases with intellectual disability and infantile motor symptoms Neuropathy, muscle cramps |
Systemic vascular involvement (aneurysms) and symptoms (renal, ocular, muscular) | Microhemorrhage or and deep intracerebral hemorrhages Lacunar infarcts Dilated perivascular spaces Leukoencephalopathy Porencephaly Intracranial calcifications |
Cockayne syndrome (DDB2, ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, ERCC6, ERCC8, GTF2H5, MPLKIP, POLH, XPA, XPC) (1st decade/Full/AR) |
Spectrum of conditions Neurodevelopmental and growth delay Impaired vision, hearing and severe neurological deficits |
Cataract Scoliosis, contractures Arthrogryposis, microphthalmia |
Calcification in the basal ganglia (possible) |
Nasu Hakola Disease—Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 and 2 (TYROBP, TREM2) (3rd decade (bone changes) 4th decade (neurological symptoms)/full/AR) |
Presenile dementia Parkinsonism Seizure |
Cyst-like bone lesions | Brain atrophy Leukodystrophy Basal ganglia calcification |
Nakajo Nishimura syndrome (PSMB8) (Childhood (Japanese)/full/AR) |
Nodular-erythema like changes Lipodystrophy Finger Joint deformities Specific inflammatory signature and hyperpyrexia Possible cardiac alteration |
Basal ganglia calcification Vessel calcifications (brain and systemic) |
|
Adams Oliver syndrome 2 (DOCK6) (Congenital/full/AR) |
Epilepsy | Facial dysmorphism Ophthalmological abnormalities (congenital cataract, rod dystrophy, vitreoretinal abnormalities, optic atrophy) Aplasia cutis congenita of the scalp Terminal transverse limb defects Systemic abnormalities (cardiac, renal, hepatic) |
Periventricular calcifications and ventricular enlargement |
Raine Syndrome (FAM20C) (77) (Congenital/full/AR) |
Neurodevelopmental delay Hydrocephalus Self-mutilating behavior |
Microcephaly Facial dysmorphism Exophthalmos, gum hyperplasia, osteosclerosis |
Punctiform periventricular and white matter calcifications |
Keutel Syndrome (MGP) (Childhood/full/AR) |
Developmental delay (mild) (epilepsy) |
Dysmorphisms due to calcification of cartilages (facial, brachytelephalangism) Hearing loss Cardiovascular defects and pulmonary stenosis, respiratory symptoms |
|
Fried Syndrome (AP1S2) (Childhood/full/X-linked recessive) |
Neurodevelopmental delay hydrocephalus Hypotonia, mental retardation, stereotypies |
Microcephaly Short stature Facial dysmorphism Optic nerve atrophy |
Basal ganglia calcification |
RAB39B (<40 years/full/X-linked) |
Parkinsonism | Juvenile Parkinsonism Intellectual disability |
Basal ganglia calcifications reported in some cases |
Hemorrhagic destruction of the brain, subependymal calcification, and cataracts (JAM3) | Seizure Severe neurological deterioration Early death |
Congenital cataract | Brain hemorrhagic destruction Subependymal calcification |
Pseudo-TORCH syndrome 1 (OCLN) (Congenital/full/AR) |
Seizure Pyramidal signs Hypotonia |
Microcephaly Possible dysmorphic features |
Calcification of the white matter, basal ganglia, cerebellum, brain stem Cortical dysgenesis |
Pseudo-TORCH syndrome 2 (USP18) (Congenital/full/AR) |
Seizure Neurological deterioration |
Microcephaly Possible dysmorphic features Immune abnormalities Intravascular coagulopathy |
Calcifications Cerebral hemorrhage Cortical dysgenesis |
Immunodeficiency 38 with basal ganglia calcification (ISG15) (1st–2nd decade/full/AR) |
Seizure | Recurrent infections | Basal ganglia and cortical calcification |
Spondyloenchondrodysplasia with immune dysregulation (ACP5) (1st decade/full/AR) |
Developmental delay Spasticity |
Spondyloenchondrodysplasia Short statue Skeletal dysplasia Immune dysregulation (multiple infections and autoimmune diseases) |
Late-onset cerebral calcification |
Rajab interstitial lung disease with brain calcifications (FARSA, FARSB) (Infancy–early childhood/full/AR) |
Delayed motor development Cognitive development can be preserved |
Delayed growth Interstitial lung disease Systemic abnormalities (hepatic, renal, skeletal) Dysmorphic features (possible immune abnormalities) |
Calcifications of the basal ganglia and cortex Possible leukoencephalopathy |
Seizures, early onset, with neurodegeneration and brain calcification (NRROS) (1st decade/full/AR) |
Seizure Developmental regression Pyramidal signs |
Brain atrophy White matter abnormalities Calcifications Possible corpus callosum hypoplasia Possible cystic degeneration of the white matter |
|
Spastic paraplegia 56, autosomal recessive (CYP2U1) (1st decade/full/AR) |
Spastic paraplegia (and also upper limbs involvement) Dystonia Cognitive impairment |
Macular dystrophy Pseudoxanthoma elasticum |
White matter lesion Atrophy of the corpus callosum Calcifications of the globus pallidus |
Down syndrome (Trisomy 21) (Congenital/full/IC) |
Mental retardation Decreased muscle tone |
Dysmorphic features, palm crease, large tongue, umbilical hernia, intestinal blockage, congenital heart disease | Basal ganglia (mostly globus pallidus) |
Pseudohypoparathyroidism (GNAS, PRKAR1A, PDE4D, PDE3A) (1st–5th decade/full/AD) |
Hypocalcemia tetani Seizure Mental retardation |
Short stature Subcutaneous calcifications Brachydactyly Hypocalcemia, hyperphosphatemia, and increased serum concentration of PTH (PTH resistance) Normal renal function |
Calcification of the basal ganglia, thalamus, subcortical white matter |