C.P.8 Clinical and pathological characterization of sporadic centronuclear myopathy by DNM2 mutations

Abstract Centronuclear myopathy (CNM) is characterized by a pathological finding of central nuclei. Sporadic or autosomal dominant CNM is linked to a gene encoding dynamin 2 ( DNM2 ) while autosomal recessive and X-linked form are related to BIN1 and MTM1 , respectively. Clinical spectrum of CNM is ranged from severe to mild phenotypes. We are to analyze clinical and pathological features of sporadic CNM patients with or without DNM2 mutations. Six patients were recruited in a basis of central nuclei on more than 30% of muscle fibers. Their clinical features and pathological details were described, and the results from DNM2 sequencing analysis were correlated. Four of the patients had DNM2 mutations scattered over three different domains and have been mostly related to mild phenotype. Four patients had the first symptoms on childhood or early adolescence while the others had developmental delay since infancy. Three of the patients displayed distal dominant weakness whereas other three patients showed proximal dominant weakness. Muscle CT scans reflected the different pattern of muscle involvement. Facial involvement and external ophthalmoplegia were variable but contractures and neck flexor weakness were common. Currently, two patients had respiratory distress, requiring ventilator support. Muscle pathology commonly revealed that a large number of muscle fibers had central nuclei (on 31.6∼100% of muscle fibers). Two of them demonstrated radial arrangement of sarcoplasmic strands, which was corresponded to the electron microscopic findings. This study detected four DNM2 mutations. DNM2 mutations appeared to make differences in clinical and pathological aspects. The patients with mutations showed later disease onset, distal dominant muscle weakness and more typical CNM pathology, such as central nuclei in almost all fibers and radial arrangement of sarcoplasmic strands. Our results may provide some guidance for genetic analyses of CNM.