Objective: In this study, we performed whole exome sequencing (WES) in Korean patients with young-onset dystonia, and investigated important factors associated with WES in dystonia.

Background: Dystonia is clinically heterogenous movement disorder and can present with various other movement disorders. The indications for genetic testing and which genes should be tested were not clearly elucidated yet.

Method: We recruited patients with young-onset (< 40 years of onset age), segmental or generalized dystonia by new MDS dystonia classification at Samsung Medical Center from 2015 to 2018. We excluded subjects with mutation in TOR1A and for persistent dystonia, PANK2 for the eye-of-tiger sign in brain MRI, PRRT2 for paroxysmal dystonia, and SGCE for myoclonus-dystonia syndrome, or subjects with focal or 2ndary dystonia. We performed WES in all enrolled subjects and confirmed with Sanger sequencing.

Results: Of total 30 recruited subjects, we found out 10 (33%) pathogenic or likely pathogenic variants related with dystonia. When we reviewed the 10 patients with relevant variants, brain imaging was helpful in 3 subjects (HTRA1, SCL20A and WDR45), clinical characteristics (paroxysmal presentation) in 2 subjects (ADCY5, and ATP1A3), and head circumstance in 1 subject (PTEN). Based on our results, WES has a positive diagnostic yield of >30% for patients with young age onset dystonia. Positive diagnostic rate was highest among childhood onset dystonia (46%). Generalized dystonia and combined other neurologic manifestations are more likely to yield a positive result.

Conclusion: Clinical exome sequencing suggests broadening of disease spectrum and uncover diagnosis of young age dystonia. Genetic diagnosis should be considered in early onset generalized dystonia combined with other neurologic manifestations.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-and-clinical-investigation-of-young-onset-dystonia-in-korea-what-can-we-learn/