Objective: To assess the involvement of genetic risk factors in implicated genes in a US cohort with musician’s focal dystonia (MFD).

Background: MFD affects 1-2% of professional musicians and the most common form is task-specific focal hand dystonia (FHD). Onset is commonly in adulthood at the peak of performance careers, and treatment is unsatisfactory. The etiology is unknown, although physical, psychological or environmental triggers in genetically susceptible individuals likely contribute. Little work has addressed the underlying genetics of MFD. Several specific variants and an overall accumulation of rare variants in the arylsulfatase G (ARSG) gene have been implicated in a combined cohort of writer’s cramp/MFD patients and a specific variant in the RAB12 gene in MFD.

Methods: We enrolled 51 musicians with FHD across two sites and assessed the associated SNPs rs11655081 and rs6199318 (ARSG) and rs143888944 (RAB12). We compared the frequency of these variants to those reported in dbSNP or the Exome Aggregation Consortium (ExAC) databases.

Results: There was male predominance (M:F 41:10), symptom onset was at 39.8±14.6 years of age (mean ± SD; range 12-67) and the majority were keyboard players. There was a family history of movement disorders in 21.5%. The ring and little fingers were most commonly involved, and 8 patients subsequently developed bilateral dystonia. Focal dystonia commonly generalized to other tasks over time. The majority (82%) were of European (Eur) ancestry, with 3 African American (Af. Am.), 4 Asian and 2 Latino patients. None of the patients had variants at rs143888944 or rs6199318. 10/51 patients had variants at rs11655081 but there were no significant differences when compared to appropriate ethnic groups in dbSNP. We did find rs62000424 (p.T444M) in ARSG in 12/51 patients with no difference in allele frequency among the Eur patients but an increased frequency among Af. Am. patients (16.7%) as compared to the Af. controls in ExAc (2.6%).

Conclusions: Compared to previously published studies, our cohort shares a similar age of onset and male predominance, but we do not see the reported associations in ARSG or RAB12.  This could be due to small sample size or more diverse ethnic background. We plan to sequence the entire ARSG gene to look for the reported preponderance of rare variants within this locus as well as examine a cohort of writer’s cramp.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/assessing-the-involvement-of-arsg-and-rab12-variants-in-musicians-focal-dystonia-from-the-us/