Adult-Onset PLEC-Related Congenital Myasthenic Syndrome-Myopathy Overlap with Upper Limb Predominant Weakness

Congenital myasthenic syndromes (CMS) are genetically heterogeneous disorders in which precise molecular diagnosis is essential for management. Pathogenic variants in PLEC are a rare cause of CMS and are frequently associated with epidermolysis bullosa simplex. We report an adult-onset case with upper limb–predominant weakness, combined myopathic and myasthenic features, and cardiomyopathy. Standard CMS gene panel testing and exome sequencing were initially non-diagnostic. Trio exome sequencing identified a second deep intronic PLEC variant, and RNA analysis demonstrated intron retention with frameshift, enabling variant reclassification and definitive diagnosis. This case expands the phenotypic spectrum of PLEC-related disease and highlights the diagnostic value of transcript-level analysis.