Table 1.
| SCA Type | Locus | Gene/protein | Genetic etiology | Clinical Manifestations (all present with ataxia) |
|---|---|---|---|---|
| SCA 1 | 6p24-p23 | ATXN1/ Ataxin 1 | CAG triplet repeat expansion (36–81 repeats); mutant protein forms nuclear aggregates | dysarthria, bulbar dysfunction, increased tone, hyperreflexia; some patients present with generalized fasciculations and wasting of extremities |
| SCA 2 | 12q24.1 | ATXN2/ Ataxin 2 | CAG triplet repeat expansion (35–64 repeats); mutant protein forms cytosplasmic aggregates | slow saccadic eye movements, hypotonia, hyporeflexia, dysarthria, nystagmus |
| SCA 3 | 14q32 | ATXN3/ Ataxin 3 | CAG triplet repeat expansion(40–200 repeats); mutant protein forms nuclear aggregates | most common; slow saccades, upper and lower motor neuropathy symptoms–abnormalities in tone and reflexes – rigidity, dystonia, muscle cramps, sleep disorders |
| SCA 4 | 16q22.1 | Unknown | Unknown | Rare; Associated with exaggerated sensoral neuropathy and extensor plantar reflexes; auditory impairments, diplopia, dysarthroa and dysphagia |
| SCA 5 | 11q13.2 | SPTBN2/ beta-III spectrin | Heterozygous mutation; mutant Beta-III spectrin affects glutamate transport in Purkinje cells | slowly progressive form of ataxia; almost pure cerebellar syndrome; dysarthria, downbeat nystagmus, impaired vibration detection, impaired lateral gaze |
| SCA 6 | 19p13.13 | CACNA1A/ αlA (P/Qtype, α12.1) | CAG triplet repeat expansion (21–33 repeats); mutant αlA (P/Qtype, α12.1) subunit of voltage-gated calcium channel causes neuronal degeneration | Pure cerebellar ataxia; dysarthria, dysphagia, diplopia, horizontal and vertical nystagmus, impaired vestibuloocular reflex |
| SCA 7 | 3p14.1 | ATXN7/Ataxin-7 | CAG triplet repeat expansion(37–200 repeats) | Progressive macular degeneration specifically affecting color vision and central visual acuity-visual abnormalities can present before ataxia; slow saccades, sensory neuropathy, anticipation, seizures |
| SCA 8 | 13q21 | ATXN8 and ATXN8OS | CTG expansion in 3′untranslated region and CAG′ repeat expansion in open reading frame (80–250 repeats); toxic gain-of-function mRNA and protein | cerebellar ataxia that affects gait, speech, swallowing, eye movements, and limb function; manifests in saccades, hyperreflexia, nystagmus, and extensor plantar responses |
| SCA 10 | 22q13 | ATXN10/ Ataxin 10 | heterozygous ATTCT pentanucleotide repeat expansion (800–4500 repeats) | oculomotor impairments, scanning dysarthria, seizures, cognitive deficits, and peripheral neuropathy |
| SCA 11 | 15q14-q21.3 | TTBK2/tau-tubulin kinase-2 | heterozygous mutation resulting in tau protein deposition | mild, pure cerebellar ataxia; horizontal and vertical nystagmus, jerky pursuits |
| SCA 12 | 5q31–5q32 | PPP2R2B/ PPP2R2B | CAG repeat expansion (66–78 repeats) at 5′ UTR of PPP2R2B-encodes regulatory subunit of brain-specific protein phosphatase | pronounced action tremor of limbs and head, bradykinesia, hyperreflexia, sensorimotor neuropathy |
| SCA 13 | 19q13.13 | KCNC3/KCNC3 | heterozygous mutation (missense mutation) | intellectual disability, motor deficits, occasional seizures, hyperreflexia, pyramidal signs |
| SCA 14 | 19q13.42 | PRKCG /PKC-gamma | heterozygous mutation(missense mutation, deletion)- most like a gain of function mutation | very rare; dysarthria, episodic axial and multifocal myoclonus, parkinsonism, myokymia, sensory loss, and cognitive deficits |
| SCA 15/16 | 3p26.1 | ITPR1 gene/ inositol 1,4,5triphophsate receptor 1 | heterozygous mutations (missense mutation, deletion) | pure gait ataxia, dysphagia, dysarthria, kinetic and postural tremors in upper extremities, gaze-evoked nystagmus, impaired vestibulo ocular reflex gain, mild executive dysfunction |
| SCA 17 | 6q27 | TBP | CAG/CAA repeat expansion (37–200 repeats) in TBP, which encodes a transcription initiation factor | dementia, dysmetira, bradykinesia, hyperreflexia, dysdiadochokinesis, chorea, intellectual impairment, psychiatric symptoms, and parkinsonism |
| SCA 18 | 7q31-q32 | unknown (IFRD1 potential candidate) | unknown | sensorimotor neuropathy with ataxia; dysmetira, muscle atrophy, hyporeflexia, and pyramidal tract signs |
| SCA 19/22 | 1p21-q21 | KCND3 | heterozygous mutation(missense mutation, deletion) in KCND3- important in cerebellar development | dysphagia and dysarthria, gaze-evoked nystagmus, hyporeflexia, tremor, intellectual impairments, and myoclonus |
| SCA 20 | 11q12 | SCA-20 | unknown | dysarthria, gait/upper limb ataxia, dysphoniam palatal tremor, hypermetric horizontal saccades, and postural tremor of arms |
| SCA 21 | 7p15.1-p21.3 | TMEM240 | heterozygous mutations (missense and nonsense) | postural and resting tremor, dysarthria, dysphagia, hyporeflexia, delayed psychomotor development, intellectual impairment, and behavioral abnormalities(apathy, aggression, impulsivity) |
| SCA 23 | 20p13 | PDYN/prodynorphin | heterozygous mutations | gait and limb ataxia, sensory neuropathy, upper extremities and head tremor, slow saccades, ocular dysmetria, and dysarthria |
| SCA 25 | 2p15-p21 | SCA-25 | unknown | sensory neuropathy, facial tics and myokymia, decreased visual acuity, urinary problems, and gastrointestinal symptoms |
| SCA 26 | 19p13.3 | EEF2 | heterozygous mutation | gait and limb ataxia, irregular visual pursuit, and dysarthria |
| SCA 27 | 13q33.1 | FGF14 | heterozygous mutation results in altered protein stability | childhood onset low amplitude, high-frequency hand tremors, unsteady gait, disrupted visual pursuit, gaze-evoked nystagmus, cognitive deficits, behavioral problems |
| SCA 28 | 18p11.21 | AFG3L2/ ATP-dependent metalloprotease | heterozygous mutations (missense mutations, small insertions or deletions) | oculomotor impairments, pyramidal tract signs,slow saccades, dysarthria, hyperrflexia of lower extremities, ptosis, mitigated vibration detection at ankles |
| SCA 29 | 3p26.1 | ITPR1 | unknown | infantile onset of impaired motor development, learning disability, dysarthria, tremor, and nystagmus |
| SCA 30 | 4q34.3-q35.1 | Unknown/ ODZ3 potential candidate | unknown | dysarthria, hypermetric saccades, lower-limb hyperreflexia, and minor pyramidal signs |
| SCA 31 | 16q21 | BEAN1/ BEAN 1 | non-coding pentanucleotide repeat insertion at Alu sequence | dyarthria, horizontal gaze nystagmus, decreased musce tone, and hearing loss |
| SCA 32 | 7q32-q33 | SCA-32 | unknown | impaired intellect, azoospermia in males |
| SCA 34 | 6q14.1 | ELOVL4/very-long-chain fatty ac | heterozygous missense mutations- loss of function imutation | neurocutaneous syndromic ataxia with childhood onset- erythrokeratodermia; at later age, severe gait ataxia, nystagmus dysarthria, mitigated tendon reflexes |
| SCA 35 | 20p13 | TGM6/ transglutaminase 6 | heterozygous mutations | gait and limb ataxia, intention tremor, dysarthria, ocular dysmetria, saccadic eye movements, hyperreflexia, torticollis, and some intellectual deficits |
| SCA 36 | 20p13 | NOP56 | pathogenic heterozygous GGCCTG repeat expansion in intron 1 (650 to 2500 repeats) | adult onset gait ataxia, tongue atrophy and fasciculations, dysarthria, oculomotor apraxia, hearing loss, motor neuron degeneration, and nystagmus |
| SCA 37 | 1p32.2 | DAB1 | pathogenic pentanucleotide ATTTC insertion within the 1p32 5′ non-coding regulatory region | early onset of dysmetric vertical saccades and irregular vertical pursuit, dysarthria, and some nystagmus |
| SCA 38 | 6p12.1 | ELOVL5 | heterozygous missense mutation | nystagmus, slow saccades, dysarthria, and distal sensory impairment |
| SCA 40 | 14q32 | CCDC88C | heterozygous missense mutation (R464H) in the coding region of the coiled-coil domain containing 88C (CCDC88C) gene | unsteady gait, dysarthria, intention tremor, ocular dysmetria, dysdiadochokinesis, hyperreflexia, and spastic paraparesis |
| SCA 41 | 4q27 | TRPC3 | heterozygous missense mutation | progressive imbalance and gait ataxia |
| SCA 42 | 17q21.33 | CACNA1G | heterozygous missense mutation | dysarthria, diplopia, saccadic persuits, decreased vibration detection, mild cognitive deficits, nystagmus, resting tremor, and mild pyramidal signs |
| SCA 43 | 3q25.2 | MME | heterozygous missense mutation | gait and limb ataxia, sensorimotor axonal polyneuropathy, pectus carinatum, pes cavus, hypometric saccades, and parkinsonism |
| SCA 44 | 6q24.3 | GRM1 | heterozygous missense mutation | childhood onset ataxia, cognitive impairments, spasticity |
| SCA 45 | 5q33.1 | FAT2 | heterozygous missense mutation | limb and gait ataxia, nystagmus, and dysarthria |
| SCA 46 | 19q13.2 | PLD3 | heterozygous missense mutation | adult onset oculomotor abnormalities and sensory impairment/ ataxia neuropathy |
| SCA 47 | 1p35.2 | PUM1 | heterozygous missense mutation | gait ataxia, dysarthria, dysmetria, some diplopia |
| SCA 48 | 16p13.3 | STUB1 | heterozygous mutation (missense and frameshift mutation) | dysarthria, dysphagia, executive function impairments, behavioral abnormalities, parkinsonism, chorea, dystonia, tremor |