Striking Phenotypic Variability in Familial TRPV4-Axonal Neuropathy Spectrum Disorder

摘要

Mutations of the transient receptor potential vanilloid cation channel 4 gene (TRPV4) have been identified in a spectrum of autosomal dominant neuropathies. These include hereditary motor and sensory neuropathy type IIC (HMSN IIC; OMIM 606071), scapuloperoneal spinal muscular atrophy (SPSMA; OMIM 181405), and congenital distal spinal muscular atrophy (OMIM 600175). Distal muscle wasting and weakness is common to all three conditions but proximal muscle involvement, scapular winging, and diaphragmatic weakness may also occur. Electro-physiology studies show a predominantly motor axonal neuropathy but sensory nerve involvement is also seen in HMSN IIC. Additional unusual features of this spectrum of neuropathies are talipes/arthrogryposis, scoliosis, bladder incontinence, sensorineu-ral hearing loss, and vocal cord paralysis (VCP). Intriguingly, TRPV4 mutations have also been identified in a newly categorized family of autosomal dominant skeletal dysplasias that include from mildest to most severe, respectively: type 3 brachyolmia (OMIM 113500), Kozlowski spondylometaphyseal dysplasia (SMD; OMIM 184252), Maroteaux spondyloepimetaphyseal dysplasia (SEMD; OMIM 184095), metatropic dysplasia (OMIM 156530), and parastremmatic dysplasia (OMIM 168400). A unifying feature of these skeletal dysplasias is short trunk with vertebral platyspondyly (flattening of vertebrae) and scoliosis. Of note, neurologic involvement and particularly VCP have not been documented in these conditions.