Reduced penetrance in hereditary motor neuropathy caused by TRPV4 Arg269Cys mutation

J Neurol. 2011 Aug;258(8):1413-21. doi: 10.1007/s00415-011-5947-7. Epub 2011 Feb 19.


Incomplete penetrance has rarely been reported in Charcot-Marie-Tooth disease. Our aim is to describe reduced penetrance in a hereditary motor neuropathy pedigree due to mutation in the transient receptor potential vallinoid 4 (TRPV4) gene. The pedigree comprised two affected members, the proband aged 44 years and her affected daughter aged 7 years, and seven additional related subjects, three of whom were subclinical gene mutation carriers aged 9, 40 and 70 years. Clinico-electrophysiological studies, MRI of lower-limb musculature and genetic testing of the TRPV4 were performed. The proband presented with a moderate facio-scapulo-peroneal syndrome, whereas her symptomatic daughter suffered from severe congenital spinal muscular atrophy with arthrogryposis, laryngomalacia, and vocal cord paresis. Electrophysiological evaluation revealed a pure motor axonal neuropathy. In the proband, MRI showed extensive and widespread fatty atrophy of lower-leg musculature, whereas in thigh musculature there was just mild distal fatty infiltration of vastus lateralis. Genetic testing revealed a heterozygous Arg269Cys mutation in the TPRV4 gene. In all three mutation carriers results from clinical and electrophysiological examination, and MRI of foot and lower-leg musculature were normal. We conclude that non-penetrance may be an integral feature of neuropathic syndromes associated with TRPV4 gene mutation.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Child
  • Electromyography
  • Female
  • Hereditary Sensory and Motor Neuropathy / genetics*
  • Hereditary Sensory and Motor Neuropathy / pathology
  • Hereditary Sensory and Motor Neuropathy / physiopathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mutation*
  • Pedigree
  • Penetrance
  • Phenotype
  • TRPV Cation Channels / genetics*


  • TRPV Cation Channels
  • TRPV4 protein, human