Objective: To test a scoring algorithm to guide genetic testing in dystonia.

Background: Recent evidence from a large multicentric study allowed to establish a scoring algorithm aiding the choice of a whole exome sequencing study (WES) in patients with dystonia (Zech et al). Defined positive predictors consist of an age at onset <20 (2 points), segmental/generalized involvement (1 point) as well as the presence of further neurological symptoms (1 to 2 points). This scoring algorithm has been validated in a multicentric cohort of prospectively recruited patients. Real life data from dystonia outpatient clinics are missing.

Method: We screened the patients regularly attending the dystonia outpatient clinic of the Innsbruck medical university excluding acquired forms (e.g. history of trauma, neuroleptic intakes etc.) as well as cases of secondary dystonia (e.g. oromandibular dystonia or blepharospasms within clinically clear atypical parkinsonism). WES studies were performed within a cooperation study with the technical University of Munich.

Results: In our dystonia outpatient clinic 368 patients with primary dystonia are regularly followed. WES was performed in 4/4 patients with score 5, 27/27 patients with score 3-4 and 138/336 patients with score £2 (total 169). WES yielded a genetic diagnosis in 3 out of 4 patients with a score of 5 (75%), in 16 out of 27 patients with a score 3-4 (59%) and in 9 out of 138 patients with a score £2 (6,5%).

Conclusion: As expected, the diagnostic yield of WES in our dystonia cohort correlates with a higher predictive score. However, our positivity rates were overall higher than previously described in an unselected prospective population (51%, 25% and 2% with a score of 5, 3 to 4 and £2 respectively). Our real-life data outline the even greater diagnostic rate of WES in the setting of a clinically well-defined dystonia population.

References: M Zech, R Jech, S Boesch, et al. Monogenic variants in dystonia: an exome-wide sequencing study. Lancet Neurol, 19 (2020), pp. 908-918

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MDS Abstracts - https://www.mdsabstracts.org/abstract/scoring-algorithm-based-genomic-testing-in-dystonia-real-life-data-from-the-outpatient-clinic/