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Neuromuscul Disord. 2017 Nov;27(11):975-985. doi: 10.1016/j.nmd.2017.05.016. Epub 2017 May 30.

Common and variable clinical, histological, and imaging findings of recessive RYR1-related centronuclear myopathy patients.

Author information

1
Departamento de Neurologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil; Department of Translational Medicine and Neurogenetics, IGBMC, INSERM U964, CNRS UMR7104, University of Strasbourg, Illkirch, France; Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institutes of Health, Bethesda, MD, USA.
2
Departamento de Neurologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.
3
Center for Research in Myology, Sorbonne University, Pitié-Salpêtrière Hospital Group, Paris, France.
4
Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institutes of Health, Bethesda, MD, USA.
5
Department of Translational Medicine and Neurogenetics, IGBMC, INSERM U964, CNRS UMR7104, University of Strasbourg, Illkirch, France.
6
Department of Radiology, DASA Laboratory, São Paulo, Brazil.
7
Servicio de Neurología y Servicio de Patologia, Hospital de Pediatría Garrahan, Buenos Aires, Argentina.
8
Department of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
9
Individualized Medical Genetics Center, Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
10
Department of Pathology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
11
Department of Pediatrics, Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
12
APHM, Dept. Neurology, Neuromuscular & ALS Reference Center, La Timone Univ. Hospital, France Aix Marseille Université, INSERM, GMGF, Marseille, France.
13
Dept. Biochemistry, Molecular Biochemistry & Genetics, Toxicology & Pharmacology, Grenoble Alpes University, GIN Inst. Neurosciences, Grenoble, France.
14
Division of Child Neurology, Department of Pediatrics, School of Medicine, Dokuz Eylül University, İzmir, Turkey.
15
Paris-Est Neuromuscular Center, APHP - GH Pitié-Salpêtrière, Paris, France.
16
Department of Translational Medicine and Neurogenetics, IGBMC, INSERM U964, CNRS UMR7104, University of Strasbourg, Illkirch, France; Department of Computer Science, ICube, UMR 7357, CNRS, Strasbourg, France.
17
Department of Computer Science, ICube, UMR 7357, CNRS, Strasbourg, France.
18
Centre National de Génotypage, Institut de Génomique, CEA, Evry, France.
19
Setor de Doenças Neuromusculares, Departamento de Neurologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
20
Department of Translational Medicine and Neurogenetics, IGBMC, INSERM U964, CNRS UMR7104, University of Strasbourg, Illkirch, France; Faculté de Médecine, Laboratoire de Diagnostic Génétique, Nouvel Hopital Civil, Strasbourg, France.
21
Departamento de Neurologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil. Electronic address: edmar.zanoteli@usp.br.

Abstract

Mutations in RYR1 give rise to diverse skeletal muscle phenotypes, ranging from classical central core disease to susceptibility to malignant hyperthermia. Next-generation sequencing has recently shown that RYR1 is implicated in a wide variety of additional myopathies, including centronuclear myopathy. In this work, we established an international cohort of 21 patients from 18 families with autosomal recessive RYR1-related centronuclear myopathy, to better define the clinical, imaging, and histological spectrum of this disorder. Early onset of symptoms with hypotonia, motor developmental delay, proximal muscle weakness, and a stable course were common clinical features in the cohort. Ptosis and/or ophthalmoparesis, facial weakness, thoracic deformities, and spinal involvement were also frequent but variable. A common imaging pattern consisted of selective involvement of the vastus lateralis, adductor magnus, and biceps brachii in comparison to adjacent muscles. In addition to a variable prominence of central nuclei, muscle biopsy from 20 patients showed type 1 fiber predominance and a wide range of intermyofibrillary architecture abnormalities. All families harbored compound heterozygous mutations, most commonly a truncating mutation combined with a missense mutation. This work expands the phenotypic characterization of patients with recessive RYR1-related centronuclear myopathy by highlighting common and variable clinical, histological, and imaging findings in these patients.

KEYWORDS:

Centronuclear myopathy; Congenital myopathies; RYR1

PMID:
28818389
DOI:
10.1016/j.nmd.2017.05.016
[Indexed for MEDLINE]

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