G.P.238: Phenotypic spectrum of three patients affected by TRPV4 mutations

Abstract

Mutations in the TRPV4 (transient receptor potential vanilloid 4) gene, encoding a non-selective cation channel, causes congenital distal spinal muscular atrophy, scapuloperoneal spinal muscular atrophy and inherited motor sensory neuropathy type 2C. Here we report the clinical phenotype of three patients belonging to 2 families that affected member fit with the previously described phenotype in the TRPV4 gene mutations. Patient 1 is the mother of patient 2, current age 44 years old. Symptoms began at 20 years old with difficulties on walking in her heels and developing progressive scapuloperoneal muscle atrophy syndrome and transient dysphonia. Currently she is able to walk independently with bilateral steppage. Marked atrophy of lower legs and scapular musculature sparing forearm and intrinsic hand muscle were observed. Axonal motor neuropathy was confirmed. Genomic studies: heterocygous, c.805C>T mutation in TRPV4 gene. Patient 2: She was born from a normal pregnancy and deliver but with clubfoot and limited knee extension. Severe motor developed was observed being unable to walk or stand up. Deep tendon reflex was abolished and axonal motor neuropathy was confirmed. Because a severe restrictive respiratory and frenic nerve involvement she presented atelectasis, pneumonias and cardio respiratory arrest needing ventilator support and tracheostomies complicated with gastric rupture in one occasion. Genetic studies confirmed the same mutation of her mother. Patient 3: An 18 year old boy had normal motor development. When he was 13 years old he complained loss of strength in upper distal limbs. Present mild weakness of flexor and extensor wrist muscles. Deep tendon reflexes were normal. Axonal motor neuropathy was confirmed. Genetic studies showed a heterocigous mutation, c.1684G>T in TRPV4 gene. TRPV4 gene mutations cause a heterogeneous group of neurodegenerative disorders, characterized by variable penetrance and phenotypic expression for the same mutation.