Dynamin 2-related centronuclear myopathy: clinical, histological and genetic aspects of further patients and review of the literature

Centronuclear myopathy (CNM) is a slowly progressive congenital myopathy with characteristic histopathological findings of chains of centrally located myonuclei in a large number of muscle fibers. Recently, different missense mutations in the dynamin 2 gene (DNM2, 19p13.2) have been shown to cause autosomal dominant CNM. We re-evaluated patients with a histopathological diagnosis of CNM and report on the clinical phenotype, the biopsy findings and the genetic results of these patients and review the current literature. Two of the three patients showed an unusually late disease onset (< 40 years). Interestingly, intramuscular nerve fascicles found in the muscle biopsy of a patient harboring the E368K DNM2 mutation contained nerve fibers with disproportionately thin myelin sheaths. Schwann cells of unmyelinated nerve fibers showed abnormal plasma membrane and basal lamina protrusions, indicating peripheral nerve involvement.