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

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

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.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Muscle, Skeletal / diagnostic imaging
  • Muscle, Skeletal / pathology
  • Mutation
  • Myopathies, Structural, Congenital / diagnostic imaging*
  • Myopathies, Structural, Congenital / genetics
  • Myopathies, Structural, Congenital / pathology*
  • Myopathies, Structural, Congenital / physiopathology
  • Phenotype
  • Ryanodine Receptor Calcium Release Channel / genetics*

Substances

  • Ryanodine Receptor Calcium Release Channel

Supplementary concepts

  • Myopathy, Centronuclear, Autosomal Recessive