Early-Onset Autosomal Dominant Myopathy with Vacuolated Fibers and Tubular Aggregates but No Periodic Paralysis, in a Patient with the c.1583G>A (p.R528H) mutation in the CACNA1S Gene

Abstract

Dominant mutations in CACNA1S gene mainly causes hypokalemic periodic paralysis (PP)(hypoPP). A 68-year-old male proband developed a progressive proximal weakness from the age of 35. Muscle biopsy showed atrophic fibers with vacuoles containing tubular aggregates. Exome sequencing revealed a heterozygous p.R528H (c.1583G>A) mutation in the CACNA1S gene. CACNA1S-related HypoPP evolving to persistent myopathy in late adulthood is a well-known clinical condition. However, isolated progressive myopathy (without PP) was only exceptionally reported and never with an early onset. Reporting a case of early onset CACNA1S-related myopathy in a patient with no HypoPP we intend to alert clinicians to consider it in the differential diagnosis of younger adult-onset myopathies especially when featuring vacuolar changes.