Beyond SGCE: expanding the clinical and molecular spectrum of KCTD17- and KCNN2-related myoclonus-dystonia

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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. W e 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.

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