Charcot-Marie-Tooth disease type 2CC due to a frameshift mutation of the neurofilament heavy polypeptide gene in an Austrian family

Neuromuscul Disord. 2019 May;29(5):392-397. doi: 10.1016/j.nmd.2019.02.007. Epub 2019 Feb 20.

Abstract

Neurofilaments are structural components of motor axons. Recently different variants resulting in translation of a cryptic amyloidogenic element of the neurofilament-heavy polypeptide (NEFH) gene have been described to cause Charcot-Marie-Tooth disease type 2CC (CMT2CC) by forming amyloidogenic toxic protein aggregation. Until now only few CMT2CC patients have been described. Clinical features include progressive muscle weakness and atrophy mainly affecting the lower limbs, hyporeflexia and distal sensory impairment. In addition to classic CMT features, some patients were reported to have increased serum creatine kinase levels, an electrophysiologic pattern suggestive for myopathies, and pyramidal signs. Ambulation is progressively impaired, most patients are non-ambulant in the 5th decade. Nerve conduction testing shows a symmetrical, distal and proximal sensorimotor axonal neuropathy. Here we describe the first Austrian pedigree suffering from CMT2CC and give an overview on the phenotype of CMT2CC described so far.

Keywords: Charcot-Marie-Tooth Type 2CC; Neurofilament heavy chain; Protein aggregation.

Publication types

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

MeSH terms

  • Adult
  • Austria
  • Charcot-Marie-Tooth Disease / genetics*
  • Charcot-Marie-Tooth Disease / pathology
  • Charcot-Marie-Tooth Disease / physiopathology
  • Fathers
  • Frameshift Mutation
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Muscle, Skeletal / diagnostic imaging
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Neurofilament Proteins / genetics*
  • Nuclear Family
  • Protein Aggregation, Pathological / genetics
  • Protein Aggregation, Pathological / pathology
  • Protein Aggregation, Pathological / physiopathology

Substances

  • Neurofilament Proteins
  • neurofilament protein H