Syndrome | Gene | Inheritance pattern | Clinical features |
Ataxia-Telangiectasia-like disease (ATLD) | MRE11 | AR | Childhood-onset, ambulant patient beyond 10 years old, ataxia, oculomotor apraxia, hypoalbuminaemia, increased sensitivity to ionizing radiation, defective DNA repair, chromosomal instability |
Ataxia with oculomotor apraxia-1 (AOA1) | APTX | AR | Ataxia, oculomotor apraxia, peripheral neuropathy, childhood-onset. No immunodeficiency and no telangiectasia, hypoalbuminaemia, secondary coenzyme Q10 deficiency |
AOA-2/autosomal recessive spinocerebellar ataxia 2 (SCAR1) | SETX | AR | Similar to AOA1, ataxia, oculomotor apraxia, peripheral neuropathy, teenage-onset, increased alpha-fetoprotein |
Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) | RFC1 | AR | Ataxia, peripheral neuropathy, impaired visually enhanced vestibulo-ocular reflex, autonomic dysfunction |
Fragile X-associated tremor ataxia syndrome (FXTAS) | FMR1 carrier | XL dominant | Usually males. Late-onset ataxia, Parkinsonism, cognitive impairment, peripheral neuropathy, autonomic dysfunction, hyperintensity of middle cerebellar peduncles |
Hereditary dystonia DYT1, dopamine responsive (DYT5A, DYT5B), DYT6 | TOR1A, GCH1, TH, THAP1 | AD | Dystonia can be focal, segmental or generalised. Some are dopamine responsive. Associated Parkinsonism or kinesigenic dyskinesia. Some adolescent/adult-onset |
Myoclonic dystonia | SGCE, RELN | AR | Myoclonus, focal or segmental dystonia, alcohol-responsive, psychiatric manifestations |
Mitochondrial ataxias | NARP (MT-ATP6) | Maternal inheritance | Sensory neuropathy, ataxia, retinitis pigmentosa, seizures, arrhythmias, cognitive impairment, maternal inheritance, variable phenotype within families |
POLG | AD, AR | Chronic progressive external ophthalmoplegia, ptosis, ataxia, neuropathy, seizures, liver failure | |
AFG3L2 | AD | Spastic ataxia, optic atrophy | |
SPG7 | AR | Spasticity, ataxia, peripheral neuropathy, dysarthria, optic atrophy, ptosis, spasticity amyotrophy, urinary sphincter disturbance | |
ARSACS (SACS) | AR | Classic triad: spasticity, ataxia, peripheral neuropathy | |
Neurodegeneration of Brain Iron Accumulation (NBIA) | WDR4 PANK2 PLA2G6 ATP13A2 C19orf12 COAS CP DCAF17 FA2H FTL | XL AR AR AR AR, AD AR AR AR AR AD | Dystonia, spasticity, optic atrophy, neuropsychiatric abnormalities, Parkinsonism. Iron accumulation in the basal ganglia |
Spinocerebellar ataxia (SCA) (SCA1- 6, 11-12,14-18, 19/22, 20, 23, 25-28, 37-38, 41-43, 45, autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCADN), dentatorubral-pallidoluysian atrophy (DRPLA), GRID2-related spinocerebellar ataxia, hypomyelinating leukoencephalopathy, pure cerebellar ataxia, rapid-onset ataxia | ATXN1, ATXN2, ATXN3, 16q22.1,SPTBN2, CACNA1A1, ATXN8, TTBK2, PPP2R2B, PRKCG, ITPR1, TBP, 7q22-q32, KCND3, 11q12, PDYN, SCA25, EEF2, FGF14, AFG3L2, 1p32, ELOVL5, TRPC3, CANCA1G, MME, FAT2, PLD3, DNMT1, ATN1, GRID2, TUBB4A, C9orf72, ATP1A3 | AD | Vary from pure ataxia to complex disease including ophthalmoplegia, slow saccades, ptosis, peripheral neuropathy, amyotrophy, deafness, retinopathy, hyperreflexia, Parkinsonism, myoclonus, chorea, head tremor, cognitive impairment, narcolepsy, atrophic lateral sclerosis |
Spinocerebellar ataxia with neuropathy (SCAN 1-3) | TDP1, SETX, COA7 | AR | Ataxia, axonal neuropathy, hyporeflexia, sometimes elevated creatine kinase, hypercholesterolemia |
Autosomal recessive spinocerebellar ataxia (SCAR): SCAR2 SCAR4 | PMPCA VPS13D | AR AR | Ataxia, cognitive impairment, dystonia, spasticity Ataxia, chorea, dystonia, spasticity |
Wilson’s disease | ATP7B | AR | Dystonia, incoordination, personality change, ataxia, liver failure, Kayser-Fleischer rings |
Alcoholic cerebellar atrophy | – | Ataxia, axonal neuropathy, myopathy, alcoholic fatty liver disease | |
Immune-mediated ataxias: primary autoimmune, anti-GAD65, coeliac disease, post-infectious | – | Late-onset, insidious, chronic or subacute, gait ataxia, stiff person syndrome, dysarthria, nystagmus, gastrointestinal symptoms |