Reduced penetrance in hereditary motor neuropathy caused by TRPV4 Arg269Cys muta

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J Neurol. 2011 Feb 19. [Epub ahead of print]

Reduced penetrance in hereditary motor neuropathy caused by TRPV4 Arg269Cys

mutation.

Berciano J, Baets J, Gallardo E, Zimo & #324; M, García A, López-Laso E, Combarros

O, Infante J, Timmerman V, Jordanova A, De Jonghe P.

Service of Neurology, University Hospital " Marqués de Valdecilla " (IFIMAV),

" Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas "

(CIBERNED), University of Cantabria (UC), 39008, Santander, Spain

Abstract

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.