Spinocerebellar Ataxias (SCA) Comprehensive Panel

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.