CMT 2C with vocal cord paresis associated with short stature and mutation in the

[Guest guest]

Neurology. 2010 Nov 30;75(22):1968-75.

CMT2C with vocal cord paresis associated with short stature and mutations in the

TRPV4 gene.

Chen DH, Sul Y, Weiss M, Hillel A, Lipe H, Wolff J, Matsushita M, Raskind W,

Bird T.

1660 S Columbian Way, S-182-GRECC, Seattle, WA 98108

Abstract

BACKGROUND: Recently, mutations in the transient receptor potential cation

channel, subfamily V, member 4 gene (TRPV4) have been reported in

Charcot-Marie-Tooth Type 2C (CMT2C) with vocal cord paresis. Other mutations in

this same gene have been described in separate families with various skeletal

dysplasias. Further clarification is needed of the different phenotypes

associated with this gene.

METHODS: We performed clinical evaluation, electrophysiology, and genetic

analysis of the TRPV4 gene in 2 families with CMT2C.

RESULTS: Two multigenerational families had a motor greater than sensory axonal

neuropathy associated with variable vocal cord paresis. The vocal cord paresis

varied from absent to severe, requiring permanent tracheotomy in 2 subjects. One

family with mild neuropathy also manifested pronounced short stature, more than

2 SD below the average height for white Americans. There was one instance of

dolichocephaly. A novel S542Y mutation in the TRPV4 gene was identified in this

family. The other family had a more severe, progressive, motor neuropathy with

sensory loss, but less remarkable short stature and an R315W mutation in TRPV4.

Third cranial nerve involvement and sleep apnea occurred in one subject in each

family.

CONCLUSION: CMT2C with axonal neuropathy, vocal cord paresis, and short stature

is a unique syndrome associated with mutations in the TRPV4 gene. Mutations in

TRPV4 can cause abnormalities in bone, peripheral nerve, or both and may result

in highly variable orthopedic and neurologic phenotypes.