A Study of a Cohort of X-Linked Myotubular Myopathy at the Clinical, Histologic, and Genetic Levels.

Background: Myotubular myopathy is a rare X-linked congenital myopathy characterized by marked neonatal hypotonia and respiratory insufficiency, facial and ocular involvement, and muscle biopsy with prominent central nuclei in the majority of muscle fibers. It is caused by mutations in MTM1, which codes for the phosphoinositides phosphatase myotubularin. In this work, we established and detailed a new cohort of six patients at the clinical, histologic, and genetic levels.

Patients And Methods: Patients were recruited after screening 3065 muscle biopsy reports from two large biopsy banks in Sao Paulo, Brazil from the years 2008 to 2013, and from referrals to a neuromuscular outpatient clinic between 2011 and 2013. We reviewed biopsy slides, evaluated patients, and Sanger sequenced MTM1 in the families.

Results: All patients but one had classic phenotypes with a stable course after a severe onset. Two patients died suddenly from hypovolemic shock. Muscle biopsies had been performed in five patients, all of whom showed a classic pattern with a predominance of centrally located nuclei and increased oxidative activity in the center of the fibers. Two patients showed necklace fibers, and two families had novel truncating mutations in MTM1.

Conclusions: X-linked myotubular myopathy is rare in the Brazilian population. Necklace fibers might be more prevalent in this condition than previously reported. Direct Sanger sequencing of MTM1 on clinical suspicion avoids the need of a muscle biopsy.