Genetic Assessment of Consecutively Recruited Dystonia Cases from a Single Center

The genetics of dystonia have been extensively investigated in population-based and multicenter cohorts. In this study, we analyzed a consecutively recruited, single-center German dystonia cohort using whole-exome sequencing (n = 252 index patients). Pathogenic or likely pathogenic variants were identified in established (n = 7) and less-established (n = 4) dystonia-associated genes, resulting in a diagnostic yield of 4.4% (11/252); all variants were heterozygous. Consistent with previous European studies, earlier age at onset (≤ 40 years; p value = 0.0218) was significantly associated with increased diagnostic yield and demonstrated acceptable predictive value (AUC = 0.76). Notably, missense variants were also associated with earlier onset (p value = 0.05; mean age 22 ± 28 years). This study (1) underscores the importance of both shared features—such as clinical characteristics associated with diagnostic yield—and distinct genetic features, including a relatively lower diagnostic rate and differences in the composition of implicated genes across cohort designs, and (2) suggests that gene panel–based sequencing approaches may be misleading and time-consuming in diagnostic settings.