Myotonia in DNM2-related centronuclear myopathy

J Neural Transm (Vienna). 2014 May;121(5):549-53. doi: 10.1007/s00702-013-1140-8. Epub 2013 Dec 24.

Abstract

Centronuclear myopathy (CNM) is a rare hereditary myopathy characterized by centrally located muscle fiber nuclei. Mutations in the dynamin 2 (DNM2) gene are estimated to account for about 50 % of CNM cases. Electromyographic recordings in CNM may show myopathic motor unit potentials without spontaneous activity at rest. Myotonic discharges, a distinctive electrical activity caused by membrane hyperexcitability, are characteristic of certain neuromuscular disorders. Such activity has been reported in only one CNM case without a known genetic cause. We sequenced the DNM2 gene and the genes associated with myotonia (CLCN1, SCN4A, DMPK and ZNF9) in a sporadic adult patient with CNM and myotonic discharges. Sequencing the entire coding region and exon-intron boundaries revealed a heterozygous c.1106g-a substitution in exon 8, resulting in a R369Q change in the DNM2. Sequencing the CLCN1, SCN4A, DMPK and ZNF9 genes ruled out mutations in these genes. This is the first report of DNM2-related CNM presenting with myotonia. The diagnosis of CNM should be considered in patients with myotonic discharges of an unknown cause.

Publication types

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

MeSH terms

  • Adult
  • Base Sequence
  • Chloride Channels / genetics
  • DNA Mutational Analysis
  • Dynamin II / genetics*
  • Electromyography
  • Female
  • Humans
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Myopathies, Structural, Congenital / complications*
  • Myopathies, Structural, Congenital / genetics*
  • Myopathies, Structural, Congenital / pathology
  • Myopathies, Structural, Congenital / physiopathology
  • Myotonia / complications*
  • Myotonia / genetics*
  • Myotonia / pathology
  • Myotonia / physiopathology
  • Myotonin-Protein Kinase / genetics
  • NAV1.4 Voltage-Gated Sodium Channel / genetics
  • RNA-Binding Proteins / genetics

Substances

  • CLC-1 channel
  • CNBP protein, human
  • Chloride Channels
  • DMPK protein, human
  • NAV1.4 Voltage-Gated Sodium Channel
  • RNA-Binding Proteins
  • SCN4A protein, human
  • Myotonin-Protein Kinase
  • Dynamin II