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


Neto O. A., Martins Moreno C. d. A., Malfatti E., Donkervoort S., Bohm J., Guimaraes J. B., ...Daha Fazla

NEUROMUSCULAR DISORDERS, cilt.27, sa.11, ss.975-985, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 27 Sayı: 11
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1016/j.nmd.2017.05.016
  • Dergi Adı: NEUROMUSCULAR DISORDERS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.975-985
  • Anahtar Kelimeler: RYR1, Centronuclear myopathy, Congenital myopathies, CENTRAL CORE DISEASE, CONGENITAL MYOPATHIES, MALIGNANT HYPERTHERMIA, RYR1 MUTATIONS, MUSCLE, GENE, SPECTRUM, RHABDOMYOLYSIS
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

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. (C) 2017 Elsevier B.V. All rights reserved.