X-linked myotubular myopathy.

X-linked myotubular myopathy (XLMTM) is a severe congenital muscle disease caused by mutation in the MTM1 gene. MTM1 encodes myotubularin (MTM1), an endosomal phosphatase that acts to dephosphorylate key second messenger lipids PI3P and PI3,5P2. XLMTM is clinically characterized by profound muscle weakness and associated with multiple disabilities (including ventilator and wheelchair dependence) and early death in most affected individuals. The disease is classically defined by characteristic changes observed on muscle biopsy, including centrally located nuclei, myofiber hypotrophy, and organelle disorganization. In this review, we highlight the clinical and pathologic features of the disease, present concepts related to disease pathomechanisms, and present recent advances in therapy development.