Adult-onset respiratory insufficiency, scoliosis, and distal joint hyperlaxity in patients with multiminicore disease due to novel Megf10 mutations

Muscle Nerve. 2016 Jun;53(6):984-8. doi: 10.1002/mus.25054. Epub 2016 Apr 25.

Abstract

Introduction: Multiminicore disease is a congenital myopathy characterized pathologically by the presence of multiple minicore structures in the sarcoplasm. Mutations in the selenoprotein N1-encoding gene (SEPN1) and ryanodine receptor 1-encoding gene (RYR1) are responsible for half of the reported cases. Mutations in multiple epidermal growth factor-like domains 10-encoding gene (MEGF10) have been identified only recently in a few patients with antenatal to infantile-onset myopathy, with and without minicore pathology.

Methods: We report 2 sisters with adult-onset respiratory insufficiency followed by development of limb weakness. Both had scoliosis, distal joint hyperlaxity, and high-arched feet.

Results: A biopsy of the right triceps muscle in 1 sister showed multiple minicore structures. She had electromyographic changes of myopathy with fibrillation potentials and myotonic discharges. Next generation sequencing identified novel compound heterozygous missense variants in MEGF10 c.230G>A (p.Arg77Gln) and c.1833T>G (p.Cys611Trp) in both sisters.

Conclusions: MEGF10 mutations can cause myopathy with adult-onset respiratory insufficiency. Muscle Nerve, 2016 Muscle Nerve 53: 984-988, 2016.

Keywords: MEGF10; joint hyperlaxity; multiminicore disease; myopathy; myotonic discharges; respiratory insufficiency; scoliosis.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Family Health
  • Female
  • Humans
  • Joint Instability / complications
  • Joint Instability / genetics*
  • Membrane Proteins / genetics*
  • Mutation / genetics*
  • Myopathies, Structural, Congenital / complications
  • Myopathies, Structural, Congenital / genetics*
  • Ophthalmoplegia / complications
  • Ophthalmoplegia / genetics*
  • Respiratory Insufficiency / complications
  • Respiratory Insufficiency / genetics*
  • Ryanodine Receptor Calcium Release Channel / deficiency*
  • Ryanodine Receptor Calcium Release Channel / genetics
  • Scoliosis / complications
  • Scoliosis / genetics*

Substances

  • MEGF10, human
  • Membrane Proteins
  • Ryanodine Receptor Calcium Release Channel

Supplementary concepts

  • Minicore Myopathy with External Ophthalmoplegia