Objective: To determine the contribution of different approaches to the clinical use of genetic tests in dystonia diagnosis.

Background: Dystonias are a heterogeneous group of hyperkinetic movement disorders (MD) characterised by involuntary sustained muscle contractions that lead to abnormal postures. Over 40 genes have been related to hereditary dystonia forms. Next-generation sequencing has been imperative to identify new genetic causes of dystonia.

Method: We conducted an observational study of a convenience sample of 81 patients with dystonia diagnosis from a Tertiary referral hospital. Data on demographic characteristics, clinical features and genetic testing was registered

Results: A molecular diagnosis was established in 24/81 (29.6%) patients. Seven patients carried pathogenic variants in SGCE gene, five in RNASEH2B, two in KMT2B, GNAL and GNAO1 genes, respectively. Six patients (n=1, each) showed variants in ATP1A3, THAP1, TOR1A, YY1, NPC1 and ADAR1. In 15 patients (62.5%) the diagnosis was confirmed with single-gene test (Aicardi-Goutières syndrome, DYT-TOR1A, DYT-THAP1, DYT-SGCE, DYT-ATP1A3) and 5 (20.8%) with NGS gene panels (DYT-SGCE, DYT-GNAL, GNAO1 encephalopathy, DYT-YY1). In 4 patients (16%) with complex features, clinical exome sequencing concluded the diagnosis (DYT-KMT2B, Niemann-Pick disease type C, GNAO1 encephalopathy).

Conclusion: In patients with a typical phenotype, single-gene test seems to be sufficient to corroborate the diagnosis. NGS gene panels or clinical exome sequencing may be useful in cases without clinical differentiators or in combined and complex forms of dystonia.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-role-of-genetic-testing-in-dystonia-diagnosis/