Charcot-Marie-Tooth disease

Charcot-Marie-Tooth (CMT) disease, also known as peroneal muscular atrophy or hereditary motor and sensory neuropothy, is among the most frequent hereditary disorders of the nervous system. The relatively homogeneous clinical phenotype involves Mainly progressive weakness and wasting of distal muscles; it starts and predominates in the peroneal muscles. Electrophysiological and pathology data distinguish two principal forms of CMT. demyelinating and axonal. More than 20 distinct genetic subtypes hove been identified to dole and other new loci and genes remain to be discovered, thus demonstrating wide genetic heterogeneity and a number of different pathophysiological mechanisms. The classification of these different forms is based on both the mode of inheritance autosomal dominant, recessive or X-linked and the neuropothy type demyelinating or axonal or "intermediate". The principal dominant forms are CMT1A, due to a duplication or point mutation in the PMP22 gene, and CMTX, due to mutations in the connexin 32 gene. Autosomal recessive forms ore more frequent in North Africa. The most common involve mutations of GDAP1 or lamin A/C and generally lead to more severe phenotypes than the dominant forms. The great genetic heterogeneity necessitates a strategy for genetic diagnosis. It is based in port on the classification of the different genetic forms and in port on the phenotypic particularities and the frequency of the responsible genes in the population under study.