Myotubular and Centronuclear Myopathies (CNM)

CNM is a group of rare and severe neuromuscular diseases that result from genetic mutations. People with CNM begin experiencing muscle weakness at any time from birth to early adulthood, and many patients die in the first 18 months of life. Those who survive longer require intense medical management and nearly uninterrupted support, including permanent ventilation, brace with head support and feeding tubes. The muscle weakness slowly worsens over time and can lead to delayed development of motor skills in childhood, such as crawling or walking, muscle pain during exercise and difficulty walking, with wheelchair use in the most severe cases. Affected muscles in CNM patients do not become fibrotic, in contrast to other neuromuscular diseases, but have a distinctive histological appearance and severely impaired function. Muscle fibers remain but are not well structured and therefore to do not function correctly. There is currently no FDA- or EMA-approved therapeutic treatment for CNM.

Three main forms of CNM have been identified. The most severe form of the disease is X-linked myotubular myopathy, or XLCNM, caused by mutations in the MTM1 gene. Mutations in the DNM2 gene result in autosomal dominant CNM, or ADCNM, and mutations in the BIN1 gene result in autosomal recessive CNM, or ARCNM.