P.249 - X-Linked myotubular myopathy (XLMTM): phenotypic variability

Abstract

X-linked myotubular myopathy (XLMTM) is usually a severe condition caused by mutations in myotubularin gen (MTM1, Xq28). MTM1 a lipid inositoide fosphatase acting in remodeling of membranes. Most of the affected patients present a severe neonatal form with hypotonia, weakness, facial diplegia, difficulties in sucking in addition to other symptoms, dying within the first months. Benign phenotypes have been described, as well as symptomatic carriers. The biopsy features are consistent with the presence of central nuclei in most fibres or “necklace” fibber appearance. We describe three cases of patients with XMLM: a severe phenotype, an intermediate phenotype and a symptomatic carrier. 1. (Male) Severe neonatal form characterized by severe hypotonia, swallowing disorder, and mechanical ventilation. EMG myopathic pattern. Muscle biopsy: small fibbers and central nuclei. Genetics: deletion of exon 1 to 15 of the MTM1 gene. He died at 2 months of age due to respiratory failure. (Male) axial hypotonic, scarce movements and respiratory distress, needing CPAP for few days. No tube feeding was required. Motor development was delayed. He had always difficulties in getting up from the floor. At 4 years of age he showed, facial weakness, weak cry, axial and head flexor muscles weakness. EMG: myopathic pattern. Muscle biopsy showed two population of fibres with Most of the “necklace” fibber appearance. Genetic: jc.605T > C in MTM1 gen. (Female) History of motor delayed, hemiatrophy, fatigability, proximal muscle weakness. EMG: myopathic pattern. Muscle biopsy: necklace fibber and central nuclei. Genetic mutation in MTM1 in heterozygosis: c.960del; p.Asp310Glufs. The XLMTM presents a phenotypic variability from severe phenotypes to symptomatic carriers. Central nuclei and necklace fibbers constitute a distinctive feature for the diagnostic orientation in mutations of MTM1 gene.