Congenital Myotubular Myopathy

Abstract

In 1966, Spiro et al. suggested the name myotubular myopathy for the histological changes observed in the biopsies from a 12-year-old boy because of the striking resemblance to the myotubes in fetal muscle. Myotubes are long, cylindrical, multinucleated cells, formed by the fusion of myoblasts. Typically, muscle biopsies have from 50 to 80% central nuclei, and affected fibers show a central zone devoid of enzyme activity. The X-linked form of the disease (MTMX) is characterized by marked neonatal hypotonia, a variable degree of external ophthalmoplegia, feeding difficulties, and respiratory insufficiency at birth. An essential differential diagnosis in neonatal case with central nuclei is congenital myotonic dystrophy. MTMX has been recognized to be due to mutations in the MTM1 gene, encoding for myotubularin protein (Table 40.1). Myotubularin belongs to a family of proteins expressed in most tissues, and it has a dual specific phosphatase activity, with a suggested role in signaling pathways involved in growth and development.