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Publications about genetic testing for neurological disorders
  1. Spinocerebellar Ataxias (SCA) Comprehensive Panel

Spinocerebellar Ataxias (SCA) Comprehensive 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 repeat expansion panel which includes repeat expansion analysis of the genes: ATXN1, ATXN2, ATXN3, ATXN7, ATXN8OS, ATXN10, ATN1, BEAN1, FXN, NOP56, PPP2R2B, TBP, CACNA1A
  • SCA comprehensive NGS Panel 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 + 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 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 susceptibility to late-onset Parkinson disease; spinocerebellar ataxia 2 AD 15
ATXN3 607047 spinocerebellar ataxia 3 AD 4
ATXN7 607640 spinocerebellar ataxia 7 AD 6
ATXN8OS 603680 susceptibility to late-onset Parkinson disease; spinocerebellar ataxia 8 AD 1
BEAN1 612051 spinocerebellar ataxia 31 AD 7
CACNA1A 601011 episodic ataxia type 2; familial hemiplegic migraine 1; spinocerebellar ataxia 6; early infantile epileptic encephalopathy, 42 AD 170
FXN 606829 Friedreich ataxia AR 21
NOP56 614154 spinocerebellar ataxia 36 AD 1
PPP2R2B 604325 spinocerebellar ataxia 12 AD 1
TBP 600075 susceptibility to late-onset Parkinson disease; spinocerebellar ataxia 17 AD 8