Gene | Typical age at onset | Suggestive clinical features | |
Autosomal dominant disorders | |||
HDL1 | PRNP | Third and fourth decades | Seizures Truncal ataxia Quick progression (death within 10 years) |
HDL2 | JPH3 | Third and fourth decades | South African ancestry Acanthocytosis Quick progression (Death within 15 years) |
HDL4 (SCA17) | TBP1 | Third to fifth decades (rare in childhood) | Cerebellar ataxia Dystonia Pyramidal features Family history of these features |
C9orf72 hexanucleotide repeat expansion | C9ORF72 | Fifth decade | Motor neurone disease/frontotemporal dementia overlap Pyramidal features Prominent early psychiatric symptoms |
DRPLA | ATN1 | Third and fourth decade | Japanese ancestry Seizures Quick progression (death within 15 years) Myoclonus prominent in juvenile cases |
SCA8 | ATXN8OS | Childhood to eighth decade | Ataxia Slow progression with normal life expectancy |
Benign hereditary chorea | TITF1(also called NKX2.1) | Infancy and early childhood | Non-progressive/very slow progression Few cognitive deficits Thyroid/respiratory disease |
Neuroferritinopathy | FTL1 | Fourth to fifth decade | Orofacial dystonia Iron deposition in basal ganglia seen on MRI Low serum ferritin |
ADCY5 mutations | ADCY5 | First to second decade | Combined dystonia and myoclonus Paroxysmal chorea Worse during sleep |
Recessive disorders | |||
HDL3 | 4p15.3 (gene unknown) | Childhood (3–4 years) | Autosomal recessive inheritance |
Chorea-acanthocytosis | VPS13A | Fourth decade | Autosomal recessive inheritance Self-mutilating behaviour Acanthocytosis Peripheral neuropathy/areflexia Raised serum creatine kinase Prominent orolingual dystonia when eating Seizures |
McLeod’s syndrome | XK | Mid-adulthood Third to fifth decade | X-linked recessive inheritance Peripheral neuropathy Acanthocytosis Cardiomyopathy Skeletal myopathy and atrophy Raised serum creatine kinase Facial tics |
Lesch-Nyhan syndrome | HPRT1 | First and second decade | X-linked recessive inheritance Seizures Self-mutilating behaviour High uric acid |
Wilson’s disease | ATP7B | First and second decade | Autosomal recessive inheritance Liver dysfunction Kayser-Fleischer rings Risus sardonicus Low plasma caeruloplasmin/ raised urinary copper excretion MR brain scan showing T2 hyperintensity in putamen, globus pallidus, brainstem and cerebellum |
Ataxia with oculomotor apraxia | APTX (AOA1) and SETX (AOA2) | First and second decade | Autosomal recessive inheritance Cerebellar ataxia Peripheral neuropathy Elevated α-fetoprotein (AOA2) Hypoalbuminaemia and Hypercholesterolaemia (AOA1) |
Friedreich’s ataxia | FXN | First and second decade | Autosomal recessive inheritance Ataxia Pyramidal signs Cardiomyopathy Skeletal abnormalities Optic atrophy Deafness Diabetes mellitus Peripheral neuropathy |
AOA, ataxia with oculomotor apraxia; DRPLA, dentatorubropallidoluysian atrophy; HDL, Huntington’s disease-like; SCA, spinocerebellar ataxia.