Table 1_Beyond SGCE: expanding the clinical and molecular spectrum of KCTD17- and KCNN2-related myoclonus-dystonia.xlsx

Myoclonus-dystonia syndrome (MDS) is a clinically and genetically heterogeneous movement disorder characterized by myoclonus and dystonia as its core features. While mutations in the epsilon-sarcoglycan gene (SGCE) account for most familial cases, heterozygous pathogenic variants in KCTD17 and KCNN2 have recently been described as novel genetic causes of MDS. We describe three patients from two Polish families presenting with progressive movement disorder combined with other features. Exome sequencing (ES) identified a novel heterozygous KCTD17 variant c.461 T > A, p.(Met154Lys) in a five-year-old girl with abnormal gait, postural instability, myoclonus, and tongue dyskinesia. In a 38-year-old woman and her 17-year-old daughter, both showing tremor, myoclonus, dystonia, and psychiatric symptoms, ES detected a heterozygous canonical splice-site c.1780-2A > G variant in KCNN2. Neuropsychological evaluation suggested a gene-specific effect of KCNN2 on psychiatric and cognitive functioning, including significant episodic memory impairment. This study broadens the clinical and molecular spectrum of KCTD17- and KCNN2-related MDS and highlights distinctive features compared with SGCE-MDS, focusing on disease progression, treatment response, and neuropsychiatric involvement. Recognition of these patterns may guide molecular diagnosis and the management of specific MDS types.