Ryanodine receptor 1 related myasthenia like myopathy responsive to pyridostigmine

Eur J Med Genet. 2023 Mar;66(3):104706. doi: 10.1016/j.ejmg.2023.104706. Epub 2023 Jan 18.

Abstract

Disease causing variants in the Ryanodine receptor 1 (RYR1) gene are a common cause for congenital myopathy and for malignant hyperthermia susceptibility. We report a 17 year old boy with congenital muscle weakness progressing to a myasthenia like myopathy with muscle weakness, fatigability, ptosis, and ophthalmoplegia. Muscle biopsy showed predominance and atrophy of type 1 fibers. Whole-exome trio sequencing revealed three variants in the RYR1-gene in the patient: c.6721C > T,p.(Arg2241*) and c.2122G > A,p.(Asp708Asn) in cis position, and the c.325C > T,p.(Arg109Trp) variant in trans. Treatment with pyridostigmine improved symptoms. This case supports that a myasthenia like phenotype is part of the phenotypic spectrum of RYR1 related disorders, and that treatment with pyridostigmine can be beneficial for patients with this phenotype.

Keywords: Malignant hyperthermia; Myasthenia; Ophthalmoplegia; RYR1 congenital myopathy; Ryanodine receptor calcium release channel; Therapeutics.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Humans
  • Male
  • Muscle Weakness / genetics
  • Muscle, Skeletal / pathology
  • Muscular Diseases* / genetics
  • Mutation
  • Phenotype
  • Pyridostigmine Bromide* / therapeutic use
  • Ryanodine Receptor Calcium Release Channel / genetics

Substances

  • Pyridostigmine Bromide
  • Ryanodine Receptor Calcium Release Channel
  • RYR1 protein, human