Should genetic testing for SCAs be included in the diagnostic workup for MSA?

Objective: To examine the prevalence of mutations in spinocerebellar ataxia (SCA) genes in patients who were clinically diagnosed with multiple system atrophy (MSA).

Methods: Genetic tests for SCA were performed in 302 of 528 patients who met the diagnostic criteria for MSA based on clinical features. Generally, when a patient had cerebellar symptoms or cerebellar atrophy on neuroimaging, genetic tests for SCA types 1, 2, 3, 6, 7, and 17, and dentatorubropallidoluysian atrophy were done, and when a patient had parkinsonism without cerebellar symptoms, genetic tests for SCA types 2, 3, and 17 were done.

Results: Mutations in SCA genes were found in 22 of the 302 patients (7.3%) with SCA17 comprising more than half of the mutation-positive cases. The age at disease onset in these 22 patients was not different compared with the 280 patients without mutations (55.9 ± 9.3 vs 59.2 ± 8.9, p = 0.102). All patients had urinary symptoms, and 10 patients also had orthostatic dizziness or orthostatic hypotension. A family history was reported in only 3 patients. Of note, dream enactment behavior suggesting REM sleep behavior disorder was reported in 9 of the 11 patients (81.8%) asked.

Conclusions: The high proportion of patients with SCA mutations in this study indicates that genetic testing for SCA should be included for patients with MSA, especially for patients with cerebellar dysfunctions.