Late-onset axial myopathy with cores due to a novel heterozygous dominant mutation in the skeletal muscle ryanodine receptor (RYR1) gene

Neuromuscul Disord. 2009 May;19(5):344-7. doi: 10.1016/j.nmd.2009.02.005. Epub 2009 Mar 19.

Abstract

Mutations in the skeletal muscle ryanodine receptor (RYR1) gene have been associated with a wide range of phenotypes including the malignant hyperthermia (MH) susceptibility trait, Central Core Disease (CCD) and other congenital myopathies characterized by early onset and predominant proximal weakness. We report a patient presenting at 77 years with a predominant axial myopathy associated with prominent involvement of spine extensors, confirmed on MRI and muscle biopsy, compatible with a core myopathy. RYR1 mutational analysis revealed a novel heterozygous missense mutation (c.119G>T; p.Gly40Val) affecting the RYR1 N-terminus, previously predominantly associated with MH susceptibility. This case expands the spectrum of RYR1-related phenotypes and suggests that MH-related RYR1 mutations may give rise to overt neuromuscular symptoms later in life, with clinical features not typically found in CCD due to C-terminal hotspot mutations. Late-onset congenital myopathies may be under-recognised and diagnosis requires a high degree of clinical suspicion.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Age of Onset
  • Aged
  • Calcium Signaling / genetics
  • DNA Mutational Analysis
  • Disease Progression
  • Genes, Dominant / genetics
  • Genetic Markers
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Heterozygote
  • Humans
  • Inclusion Bodies / metabolism
  • Inclusion Bodies / pathology
  • Male
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Mutation / genetics*
  • Myopathy, Central Core / genetics*
  • Myopathy, Central Core / metabolism*
  • Myopathy, Central Core / pathology
  • Ryanodine Receptor Calcium Release Channel / genetics*

Substances

  • Genetic Markers
  • Ryanodine Receptor Calcium Release Channel