Phenotype variability and histopathological findings in patients with a novel DNM2 mutation

Mutations of Dynamin 2 (DNM2) are responsible for several forms of neuromuscular disorder such as centronuclear myopathy, Charcot-Marie-Tooth disease (CMT) dominant intermediate type B, CMT 2M, and lethal congenital contracture syndrome 5. We describe a young man manifesting as length-dependent sensorimotor neuropathy with hypertrophic cardiomyopathy, but his mother only had very mild symptoms of peripheral neuropathy. The electrophysiological data meet the criteria of intermediate CMT. The main pathological findings of sural nerve biopsy reveal a severe loss of large myelinating fibers and some clusters of regenerative fibers in fascicles, which are consistent with an axonal neuropathy. However, myopathological changes show a chronic myopathy-like pattern characterized by great variations of fiber size, increased connective tissue, rimmed vacuoles and predominance of type 2 fibers. A novel DNM2 mutation (p.G359D) in the middle domain is identified, which is highly evolutionarily conserved. DNM2-related CMT disease is phenotypically heterogeneous in age at onset, clinical features and electrophysiological changes. The histopathological findings indicate the coexistence of typical axonal neuropathy and chronic myopathy in DNM2-related neuromuscular diseases.