Objective: To report a familial case of Myoclonus-Dystonia Syndrome caused by an SGCE splice-site variant, highlighting the classic maternal imprinting mechanism and the clinical diagnostic utility of pedigree mapping in identifying inherited movement disorders.

Background: Myoclonus-Dystonia Syndrome (MDS) is a rare movement disorder characterized by myoclonic jerks and dystonic postures, frequently associated with variants in the epsilon-sarcoglycan (SGCE) gene. SGCE follows a maternal imprinting pattern, where clinical symptoms typically manifest only when the variant is inherited paternally.

Method: A detailed clinical assessment was performed on two siblings presenting with progressive involuntary movements. The clinical history and a multi-generational pedigree were established through clinical interviews. Genomic data were obtained from whole-exome sequencing (WES) reports provided by the patients. We reviewed these genetic findings and integrated them with the clinical phenotype and the pedigree to confirm the genetic etiology.

Results: The 16-year-old male and his 22-year-old sister both presented with progressive myoclonic jerks and dystonic posturing. The brother exhibited truncal myoclonus and lower limb dystonia, while the sister had episodic limb tremors triggered by stress. Genetic testing identified a heterozygous splice-site variant in the SGCE gene (c.825+3_825+6del) in both siblings, inherited from their asymptomatic father. The pedigree revealed that two maternal uncles of the father (the siblings’ grand-uncles) suffered from the same movement disorder. This inheritance pattern confirms paternal transmission, which is perfectly consistent with the maternal imprinting mechanism of the SGCE gene.

Conclusion: The clinical presentation of these two siblings, coupled with the SGCE variant and the clear paternal inheritance pattern, confirms the diagnosis of Myoclonus-Dystonia Syndrome. This case demonstrates that the combination of targeted genetic review and precise pedigree analysis is definitive for diagnosing imprinted disorders. The presence of a paternal carrier and symptomatic offspring, supported by affected senior male relatives in the lineage, remains a robust diagnostic indicator for SGCE-related MDS.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/familial-myoclonus-dystonia-associated-with-sgce-variant-in-a-chinese-family-clinical-and-genetic-characterization-of-two-siblings/