C.P.11 Centronuclear and myotubular myopathies: Clinical, histological and molecular findings in a large series of Brazilian patients

• Published in: Neuromuscular disorders : NMD Vol. 22; no. 9; p. 844
• Main Authors: Abath, O, Silva, M.R, Pesquero, J.B, Oliveira, A.S.B, Carvalho, M, Chadi, G, Reed, U.C, Zanoteli, E
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-10-2012
• Subjects: Indexing in process; Neurology
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/j.nmd.2012.06.139

Abstract Myotubular and centronuclear myopathies (MTM/CNM) are congenital muscle diseases with a wide clinical spectrum and typical histopathological findings of nuclear centralizations. Four genes have been implicated in different clinical forms: MTM1 in severe X-linked cases, DNM2 in autosomal dominant adult-onset cases, BIN1 in autosomal recessive childhood-onset cases, and RYR1 in a few cases. Moreover, any of these genes can cause sporadic cases, and about half of all CNM/MTM cases end up without a molecular diagnosis. In this work, we present clinical, histopathological and preliminary molecular data of an original series of 27 Brazilian patients with CNM/MTM. Of these, 20 cases have features compatible with CNM and seven with MTM. All MTM patients had a typical history of X-linked inheritance with profound neonatal hypotonia and respiratory insufficiency and typical myotube-like features on muscle biopsy. None had acquired ambulation, and some are still ventilator-dependent. CNM cases had a wide phenotypical variation. Most cases were sporadic and had typical craniofacial weakness and hypotonia. However, age of onset varied from neonatal to adolescence and severity ranged from mild ambulatory cases to severe non ambulatory cases with respiratory compromise. In addition to typical CNM histopathological findings, we have found cases with fiber architecture disorganization (minicores, necklace fibers). Molecular study of these cases is still ongoing. A number of cases have mutations that have been previously described, such as E368K on DNM2 gene. Among the new mutations, we have found a nonsense mutation in MTM1 (c.139C>T) on a severe case of a 2-year old boy affected by MTM, and a heterozygous mutation in DNM2 (c.1279T>G) on a sporadic childhood-onset 17-year old girl. This work will help advance our knowledge of these diseases by establishing correlations between phenotypes and molecular mechanisms.