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 SCA subtypes caused by repeat expansions included in the panel5

GeneSCA Mode of Inheritance Repeat expansion Normal rangePathological range
ATXN1SCA1 AD CAG6-35 >39 (39-82) 5
ATXN2 SCA2 AD CAG<31 >33 (33-200) 6
ATXN3 SCA3 AD CAG12-4460-87 7
CACNA1A SCA6 AD CAG<1820-30 8, 9
ATXN7 SCA7 AD CAG10-19>36 (37-460) 10, 
ATXN8OS SCA8 AD (CTA·TAG)n(CTG·CAG)n15-50>71-1300 12
ATXN10 SCA10 AD ATTCT10-32800-4500 13
PPP2R2B SCA12 AD CAG4-3266-78 14
TBP SCA17 AD CAG/CAA25-40>49 (50-66) 15, 16
BEAN1 SCA31 AD (TGGAA)(n)unknown2,8-3,5 kb 17, 18
NOP56 SCA36 AD GGCCTG3-14>650 19, 20
FXN FRDA AR GAA5-33>66-1300 21, 22, 23
ATN1 DRPLA AD CAG6-35>48 (48-93) 25, 26

Abbreviations: SCA-Spinocerebellar ataxia; FRDA- Friedreich ataxia; DRPLA- Dentatorubral-pallidoluysian atrophy


Table 2: Overview of other SCA subtypes and related ataxia syndromes included in the panel

Gene (OMIM)Chr.locus Mode of Inheritance Associated/allelic disorders
ABCB7 (300135) Xq13.3 X-linked Anemia, sideroblastic, with ataxia (301310)
ABHD12 (613599) 20p11.21 AR Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (612674)
ABHD5 (604780) 3p21.33 AR Chanarin-Dorfman syndrome (275630)
ACADVL (609575) 17p13.1 AR VLCAD deficiency (201475)
AFG3L2 (604581) 18p11.21 AR SPAX5 (614487); SCA28 (610246)
ANO10 (613726) 3p22.1-p21.3 AR SCAR10 (613728)
APTX (606350) 9p21.1 AR AOA (208920)
ATCAY (608179) 19p13.3 AR Ataxia, cerebellar, Cayman type (601238)
ATM (607585) 11q22.3 AR Ataxia-telangiectasia (208900)
ATP2B3 (300014) Xq28 X-linked SCAX1 (302500)
CA8 (114815) 8q12.1 AR Cerebellar ataxia, mental retardation and disequilibrium syndrome 3 (613227)
CACNA1A (601011) 19p13.13 AD SCA6 (183086); EA2 (108500)
CCDC88C (611204) 14q32.11-q32.12 AD SCA40 (616053)
COQ8A (606980) 1q42.13 AR Coenzyme Q10 deficiency 4 (612016)
CWF19L1 (616120) 10q24.31  AR SCAR17 (616127)
DNMT1 (126375) 19p13.2 AD ADCADN (604121) 
EEF2 (130610) 19p13.3 AD SCA26 (609306)
ELOVL4 (605512) 6q14.1 AD SCA34 (133190)
ELOVL5 (611805) 6p12.1 AD SCA38 (615957)
FGF14 (601515) 13q33.1 AD SCA27 (609307)
FXN (606829) 9q21.11 AR Friedreich ataxia  (229300)
GRID2 (602368) 4q22.1-q22.2 AR SCAR18 (616204)
GRM1 (604473) 6q24.3 AD, AR SCA44 (617691); SCAR13 (614831)
ITPR1 (147265) 3p26.1 AD SCA15 (606658); SCA29 (117360)
KCNC3(176264) 19q13.33 AD SCA13 (605259)
KCND3 (605411) 1p13.2 AR SCA19 (607346)
PDYN (131340) 20p13 AD SCA23 (610245)
PRKCG (176980) 19q13.42 AD SCA14 (605361)
RUBCN (613516) 3q29 AR SCAR15 (615705)
SACS (604490) 13q12.12 AR Spastic ataxia, Charlevoix-Saguenay type  (270550)
SETX (608465) 9q34.13 AR SCAR1 (606002)
SIL1 (608005) 5q31.2  AR Marinesco-Sjogren syndrome (248800)
SLC1A3 (600111) 5p13.2 AD EA6 (612656)
SPTBN2 (604985) 11q13.2 AD, AR SCA5 (600224); SCAR14 (615386)
STUB1 (607207) 16p13.3 AR SCAR16 (615768)
SYNE1 (608441) 6q25.2 AR SCAR8 (610743)
SYT14 (610949) 1q32.2 AR SCAR11 (614229)
TDP1 (607198) 14q32.11 AR SCAR  with axonal neuropathy (607250)
TGM6 (613900) 20p13 AD SCA35 (613908)
TPP1 (607998) 11p15.4 AR SCAR7 (609270)
TTBK2 (611695) 15q15.2 AD SCA11 (604432)
TTPA (600415) 8q12.3 AR Ataxia with isolated vitamin E deficiency (277460)
TWNK (606075) 10q24.31 AR, AD

Mitochondrial DNA depletion syndrome 7 (hepatocerebral type) (271245); Perrault syndrome 5 (616138);  PEOA3 (609286)

VAMP1 (185880) 12p13.31 AD SPAX1 (108600)
WWOX (605131) 16q23.1-q23.2 AR SCAR12 (614322)

Abbreviations: SPAX-Spastic ataxia autosomal recessive, SCA-Spinocerebellar ataxia; SCAR-Spinocerebellar ataxia autosomal recessive; SCAX-Spinocerebellar ataxia X-linked; AOA-Ataxia-oculomotor apraxia syndrome, EA-Episodic ataxia; ADCADN-Autosomal dominant cerebellar ataxia deafness and narcolepsy; PEAO- Progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal dominant