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A pathogenic hexanucleotide (GGGGCC) repeat expansion in the first intron of C9orf72 has been identified in a Belgian family with teenage-onset progressive myoclonic epilepsy. The proband, a 33-year-old woman, developed epilepsy at age 15 and multifocal myoclonus with progressive cognitive decline by age 18. Genetic testing revealed the C9orf72 expansion co-segregating in two additional affected relatives, consistent with autosomal dominant inheritance in three individuals (PMID:29352102). Brain biopsy demonstrated characteristic p62-positive neuronal cytoplasmic inclusions, aligning with known C9orf72 neuropathology (PMID:29352102).
These data provide limited but compelling evidence for C9orf72 repeat expansions as a cause of juvenile-onset progressive myoclonic epilepsy. While this single-family report warrants further study, C9orf72 testing should be considered in PME patients—especially those with psychiatric or cognitive features—to guide diagnosis, genetic counseling, and early intervention. Key take-home: C9orf72 expansions extend beyond ALS/FTD to include PME, informing clinical testing strategies.
Gene–Disease AssociationLimitedSingle family report with a C9orf72 repeat expansion segregating in proband and two affected relatives Genetic EvidenceLimitedOne familial case with three affected individuals and co-segregation of the repeat expansion (PMID:29352102) Functional EvidenceLimitedBrain biopsy showed p62-positive inclusions consistent with C9orf72 pathology (PMID:29352102) |