Osorio Abath Neto1, Marina Rodrigues E Silva2, Cristiane de Araújo Martins1, Acary de Souza Bulle Oliveira3, Umbertina Conti Reed1, Valérie Biancalana4, João Bosco Pesquero2, Jocelyn Laporte5, Edmar Zanoteli6. 1. Departamento de Neurologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil. 2. Departamento de Biofísica, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. 3. Setor de Doenças Neuromusculares, Departamento de Neurologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. 4. Faculté de Médecine, Laboratoire de Diagnostic Génétique, Nouvel Hopital Civil, Strasbourg, France; Department of Translational Medicine and Neurogenetics, IGBMC, INSERM U964, CNRS UMR7104, University of Strasbourg, Collège de France, Illkirch, France. 5. Department of Translational Medicine and Neurogenetics, IGBMC, INSERM U964, CNRS UMR7104, University of Strasbourg, Collège de France, Illkirch, France. 6. Departamento de Neurologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil. Electronic address: edmar.zanoteli@usp.br.
Abstract
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.
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.
Authors: Kimberly Amburgey; Etsuko Tsuchiya; Sabine de Chastonay; Michael Glueck; Rachel Alverez; Cam-Tu Nguyen; Anne Rutkowski; Joseph Hornyak; Alan H Beggs; James J Dowling Journal: Neurology Date: 2017-08-25 Impact factor: 9.910