Publications about genetic testing for neurological disorders
  1. Spinocerebellar ataxias (SCA) comprehesive panel

Spinocerebellar ataxias (SCA) comprehesive panel

August 16, 2018

Disease summary:

Spinocerebellar ataxias (SCA) are a group of hereditary neurological disorders characterized by slowly progressive ataxia accompanied by cerebellar degeneration. Ataxia is gait imbalance associated with limb incoordination and loss of fine and gross motor control 1,2,3,4.

The most common types of SCA are caused by nucleotide repeat expansions in genes (Table 1), with the onset and severity of disease depending on the repeat size. Within the same gene, larger expansions can cause a more severe and earlier-onset disease, while shorter expansions cause later-onset disease with a milder phenotype.

More than 40 different genes are known to cause SCA which cause autosomal-dominant, autosomal-recessive, and X-linked spinocerebellar ataxias (Tables 1 and 2)5-26


Autosomal dominant, Autosomal recessive, X-linked

1-9/100,000 for all SCAs 2, 3

1-5/100,000 for autosomal dominant cerebellar ataxias (ADCA) 2, 3

3/100,000 for autosomal recessive forms (SCAR) 3  

Major clinical findings specific for ataxia include the following 1, 2, 4, 5:

  • Gait imbalance and uncoordinated walk (ataxia)
  • Dysarthria (abnormal speech)
  • Abnormal involuntary eye movements (gaze palsies, slowed saccades, ocular “stare”, blepharospasm, ptosis)
  • Classic cerebellar signs (like dysmetria, dysdiadochokinesia, intention tremor, etc.)

Less common clinical symptoms 1, 4, 5:

  • Peripheral neuropathy
  • Seizures
  • Hearing loss
  • Visual loss with retinopathy
  • Cognitive decline, dementia, learning difficulties
  • Presence of the specific clinical features
  • Presence of characteristic diagnostic imaging  features
  • Identification of a repeat expansion in one of the following genes: ATXN1, ATXN2, ATXN3, ATXN7, ATXN8OS, ATXN10, ATN1, BEAN1, FXN, NOP56, PPP2R2B, TBP, CACNA1A (Table 1)
  • Identification of pathogenic variant(s) in one of the following genes (Table 2): ABCB7, ABHD12, ABHD5, ACADVL, AFG3L2, ANO10, APTX, ATCAY, ATM, ATP2B3, CA8, CACNA1A, CCDC88C, COQ8A, CWF19L1, DNMT1, EEF2, ELOVL4, ELOVL5, FGF14, FXN, GRID2, GRM1, ITPR1, KCNC3, KCND3, PDYN, PRKCG, RUBCN, SACS, SETX, SIL1, SLC1A3, SLC2A1, SPG7, SPTBN2, STUB1, SYNE1, SYT14, TDP1, TGM6, TPP1, TTBK2, TTPA, TWNK, VAMP1, WWOX, ZNF592

There is no known cure for spinocerebellar ataxia. There are several ongoing clinical trials to test new, potential drugs for SCA. Currently, supportive treatment and management of affected individuals depend on the predominant signs and symptoms present in each person:

  • Physical therapy (fall prevention)
  • Special devices (e.g., cane, crutches) for mobility
  • Speech therapy
  • Specific medications to treat sleep disturbances 
  • Fragile X Tremor and ataxia syndrome (FXTAS) caused by increased CGG repeats in the FMR1 gene
  • Ataxia with isolated vitamin E deficiency
  • Ataxia-telangiectasia caused by pathogenic variant in gene ATM
  • Ataxia oculomotor apraxia caused by pathogenic variants in APTX or SETX
  • Angelman syndrome caused by pathogenic variants in UBE3A gene or chr15q11.2 abnormalities
  • Ataxic cerebral palsy caused by pathogenic variants in CPAT1
  • Refsum disease caused by pathogenic variants in PHYH or PEX7

To confirm/establish the diagnosis, CENTOGENE offers the following tests:

  • SCA comprehensive NGS Panel Plus which includes sequencing of the genes ABCB7, ABHD12, ABHD5, ACADVL, ADCK3, AFG3L2, ANO10, APTX, ATCAY, ATM, ATP2B3, C10ORF2, CA8, CACNA1A, CCDC88C, CWF19L1, DNMT1, EEF2, ELOVL4, ELOVL5, FGF14, FXN, GRID2, GRM1, ITPR1, KCNC3, KCND3, RUBCN, PDYN, PRKCG, SACS, SETX, SIL1, SLC1A3, SPG7, SPTBN2, STUB1, SYNE1, SYT14, TDP1, TGM6, TPP1, TTBK2, TTPA, VAMP1, WWOX, ZNF592; and repeat expansion analysis of the genes: ATXN1, ATXN2, ATXN3, ATXN7, ATXN8OS, ATXN10, ATN1, BEAN1, FXN, NOP56, PPP2R2B, TBP, CACNA1A
  • SCA comprehensive NGS Panel Plus + CNV which includes sequencing and repeat expansion analysis  and additionally detection of large deletions and duplications from the NGS data
  • Individuals with a positive family history of SCA
  • Individuals with most common symptoms of SCA (regardless of family history)

Confirmation of a clinical diagnosis through genetic testing of SCA can allow for genetic counseling and may direct medical management.


Table 1: Overview of genes included in SCA comprehensive panel

Gene OMIM (Gene) Associated diseases (OMIM) Inheritance CentoMD® exclusive variant numbers (++)
ABCB7 300135 Anemia, sideroblastic, with ataxia XL R 1
ABHD12 613599 Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract AR 0
ABHD5 604780 Chanarin-Dorfman syndrome AR 7
ACADVL 609575 VLCAD deficiency AR 32
AFG3L2 604581 Spinocerebellar ataxia 28; Spastic ataxia 5, autosomal recessive AD, AR 20
ANO10 613726 Spinocerebellar ataxia, autosomal recessive 10 AR 4
APTX 606350 Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia AR 31
ATCAY 608179 Ataxia, cerebellar, Cayman type AR 1
ATM 607585 Breast cancer, susceptibility to; Ataxia-telangiectasia AD, AR 73
ATP2B3 300014 ?Spinocerebellar ataxia, X-linked 1 XL R 3
CA8 114815 Cerebellar ataxia and mental retardation with or without quadrupedal locomotion 3 AR 0
CACNA1A 601011 Episodic ataxia, type 2; Migraine, familial hemiplegic, 1; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia; Spinocerebellar ataxia 6; Epileptic encephalopathy, early infantile, 42 AD 164
CCDC88C 611204 Hydrocephalus, nonsyndromic, autosomal recessive; ?Spinocerebellar ataxia 40 AD, AR 7
COQ8A 606980 Coenzyme Q10 deficiency, primary, 4 AR 38
CWF19L1 616120 Spinocerebellar ataxia, autosomal recessive 17 AR 2
DNMT1 126375 Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant; Neuropathy, hereditary sensory, type IE AD 49
EEF2 130610 ?Spinocerebellar ataxia 26 AD 5
ELOVL4 605512 Spinocerebellar ataxia 34; Stargardt disease 3; Ichthyosis, spastic quadriplegia, and mental retardation AD, AR 4
ELOVL5 611805 Spinocerebellar ataxia 38 AD 5
FGF14 601515 Spinocerebellar ataxia 27 AD 18
FXN 606829 Friedreich ataxia; Friedreich ataxia with retained reflexes AR 21
GRID2 602368 Spinocerebellar ataxia, autosomal recessive 18 AR 8
GRM1 604473 Spinocerebellar ataxia, autosomal recessive 13; Spinocerebellar ataxia 44 AD, AR 4
ITPR1 147265 Spinocerebellar ataxia 29, congenital nonprogressive; Gillespie syndrome; Spinocerebellar ataxia 15 AD, AR 88
KCNC3 176264 Spinocerebellar ataxia 13 AD 18
KCND3 605411 Spinocerebellar ataxia 19; Brugada syndrome 9 AD 13
PDYN 131340 Spinocerebellar ataxia 23 AD 8
PRKCG 176980 Spinocerebellar ataxia 14 AD 35
RUBCN 613516 ?Spinocerebellar ataxia, autosomal recessive 15 AR 1
SACS 604490 Spastic ataxia, Charlevoix-Saguenay type AR 29
SETX 608465 Amyotrophic lateral sclerosis 4, juvenile; Spinocerebellar ataxia, autosomal recessive 1 AD, AR 79
SIL1 608005 Marinesco-Sjogren syndrome AR 6
SLC1A3 600111 Episodic ataxia, type 6 AD 15
SLC2A1 138140 Dystonia 9; GLUT1 deficiency syndrome 1, infantile onset, severe; Stomatin-deficient cryohydrocytosis with neurologic defects; GLUT1 deficiency syndrome 2, childhood onset; Epilepsy, idiopathic generalized, susceptibility to, 12 AD, AR 35
SPG7 602783 Spastic paraplegia 7, autosomal recessive AD, AR 49
SPTBN2 604985 Spinocerebellar ataxia 5; Spinocerebellar ataxia, autosomal recessive 14 AD, AR 49
STUB1 607207 Spinocerebellar ataxia, autosomal recessive 16 AR 4
SYNE1 608441 Spinocerebellar ataxia, autosomal recessive 8; Emery-Dreifuss muscular dystrophy 4, autosomal dominant AD, AR 97
SYT14 610949 Spinocerebellar ataxia, autosomal recessive 11 AR 2
TDP1 607198 Spinocerebellar ataxia, autosomal recessive with axonal neuropathy 0
TGM6 613900 Spinocerebellar ataxia 35 AD 21
TPP1 607998 Ceroid lipofuscinosis, neuronal, 2; Spinocerebellar ataxia, autosomal recessive 7 AR 21
TTBK2 611695 Spinocerebellar ataxia 11 AD 26
TTPA 600415 Ataxia with isolated vitamin E deficiency AR 9
TWNK 606075 Mitochondrial DNA depletion syndrome 7 (hepatocerebral type); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3; Perrault syndrome 5 AD, AR 3
VAMP1 185880 Spastic ataxia 1, autosomal dominant AD 15
WWOX 605131 Esophageal squamous cell carcinoma, somatic; Spinocerebellar ataxia, autosomal recessive 12; Epileptic encephalopathy, early infantile, 28 AR 16
ZNF592 613624 1

Table 2: Overview of genes included in SCA sequencing panel

Gene OMIM (Gene) Associated diseases (OMIM) Inheritance CentoMD® exclusive variant numbers (++)
ABCB7 300135 Anemia, sideroblastic, with ataxia XL R 1
ABHD12 613599 Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract AR 0
ABHD5 604780 Chanarin-Dorfman syndrome AR 7
ACADVL 609575 VLCAD deficiency AR 32
AFG3L2 604581 Spinocerebellar ataxia 28; Spastic ataxia 5, autosomal recessive AD, AR 20
ANO10 613726 Spinocerebellar ataxia, autosomal recessive 10 AR 4
APTX 606350 Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia AR 31
ATCAY 608179 Ataxia, cerebellar, Cayman type AR 1
ATM 607585 Breast cancer, susceptibility to; Ataxia-telangiectasia AD, AR 73
ATP2B3 300014 ?Spinocerebellar ataxia, X-linked 1 XL R 3
CA8 114815 Cerebellar ataxia and mental retardation with or without quadrupedal locomotion 3 AR 0
CACNA1A 601011 Episodic ataxia, type 2; Migraine, familial hemiplegic, 1; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia; Spinocerebellar ataxia 6; Epileptic encephalopathy, early infantile, 42 AD 164
CCDC88C 611204 Hydrocephalus, nonsyndromic, autosomal recessive; ?Spinocerebellar ataxia 40 AD, AR 7
COQ8A 606980 Coenzyme Q10 deficiency, primary, 4 AR 38
CWF19L1 616120 Spinocerebellar ataxia, autosomal recessive 17 AR 2
DNMT1 126375 Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant; Neuropathy, hereditary sensory, type IE AD 49
EEF2 130610 ?Spinocerebellar ataxia 26 AD 5
ELOVL4 605512 Spinocerebellar ataxia 34; Stargardt disease 3; Ichthyosis, spastic quadriplegia, and mental retardation AD, AR 4
ELOVL5 611805 Spinocerebellar ataxia 38 AD 5
FGF14 601515 Spinocerebellar ataxia 27 AD 18
FXN 606829 Friedreich ataxia; Friedreich ataxia with retained reflexes AR 21
GRID2 602368 Spinocerebellar ataxia, autosomal recessive 18 AR 8
GRM1 604473 Spinocerebellar ataxia, autosomal recessive 13; Spinocerebellar ataxia 44 AD, AR 4
ITPR1 147265 Spinocerebellar ataxia 29, congenital nonprogressive; Gillespie syndrome; Spinocerebellar ataxia 15 AD, AR 88
KCNC3 176264 Spinocerebellar ataxia 13 AD 18
KCND3 605411 Spinocerebellar ataxia 19; Brugada syndrome 9 AD 13
PDYN 131340 Spinocerebellar ataxia 23 AD 8
PRKCG 176980 Spinocerebellar ataxia 14 AD 35
RUBCN 613516 ?Spinocerebellar ataxia, autosomal recessive 15 AR 1
SACS 604490 Spastic ataxia, Charlevoix-Saguenay type AR 29
SETX 608465 Amyotrophic lateral sclerosis 4, juvenile; Spinocerebellar ataxia, autosomal recessive 1 AD, AR 79
SIL1 608005 Marinesco-Sjogren syndrome AR 6
SLC1A3 600111 Episodic ataxia, type 6 AD 15
SLC2A1 138140 Dystonia 9; GLUT1 deficiency syndrome 1, infantile onset, severe; Stomatin-deficient cryohydrocytosis with neurologic defects; GLUT1 deficiency syndrome 2, childhood onset; Epilepsy, idiopathic generalized, susceptibility to, 12 AD, AR 35
SPG7 602783 Spastic paraplegia 7, autosomal recessive AD, AR 49
SPTBN2 604985 Spinocerebellar ataxia 5; Spinocerebellar ataxia, autosomal recessive 14 AD, AR 49
STUB1 607207 Spinocerebellar ataxia, autosomal recessive 16 AR 4
SYNE1 608441 Spinocerebellar ataxia, autosomal recessive 8; Emery-Dreifuss muscular dystrophy 4, autosomal dominant AD, AR 97
SYT14 610949 Spinocerebellar ataxia, autosomal recessive 11 AR 2
TDP1 607198 Spinocerebellar ataxia, autosomal recessive with axonal neuropathy 0
TGM6 613900 Spinocerebellar ataxia 35 AD 21
TPP1 607998 Ceroid lipofuscinosis, neuronal, 2; Spinocerebellar ataxia, autosomal recessive 7 AR 21
TTBK2 611695 Spinocerebellar ataxia 11 AD 26
TTPA 600415 Ataxia with isolated vitamin E deficiency AR 9
TWNK 606075 Mitochondrial DNA depletion syndrome 7 (hepatocerebral type); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3; Perrault syndrome 5 AD, AR 3
VAMP1 185880 Spastic ataxia 1, autosomal dominant AD 15
WWOX 605131 Esophageal squamous cell carcinoma, somatic; Spinocerebellar ataxia, autosomal recessive 12; Epileptic encephalopathy, early infantile, 28 AR 16
ZNF592 613624 1

Table 3: Overview of genes included in SCA subtypes caused by repeat expansions

Gene OMIM (Gene) Associated diseases (OMIM) Inheritance CentoMD® exclusive variant numbers (++)
ATN1 607462 Dentatorubro-pallidoluysian atrophy AD 8
ATXN1 601556 Spinocerebellar ataxia 1 AD 0
ATXN10 611150 Spinocerebellar ataxia 10 AD 0
ATXN2 601517 Parkinson disease, late-onset, susceptibility to; Amyotrophic lateral sclerosis, susceptibility to, 13; Spinocerebellar ataxia 2 AD, Isolated cases, MF 15
ATXN3 607047 Machado-Joseph disease AD 4
ATXN7 607640 Spinocerebellar ataxia 7 AD 6
ATXN8OS 603680 Spinocerebellar ataxia 8 AD 1
BEAN1 612051 Spinocerebellar ataxia 31 AD 7
CACNA1A 601011 Episodic ataxia, type 2; Migraine, familial hemiplegic, 1; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia; Spinocerebellar ataxia 6; Epileptic encephalopathy, early infantile, 42 AD 164
FXN 606829 Friedreich ataxia; Friedreich ataxia with retained reflexes AR 21
NOP56 614154 Spinocerebellar ataxia 36 AD 1
PPP2R2B 604325 Spinocerebellar ataxia 12 AD 1
TBP 600075 Parkinson disease, susceptibility to; Spinocerebellar ataxia 17 AD, Isolated cases, MF 5