Charcot Marie Tooth disease

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Presse Med. 2009 Jan 7.

Charcot-Marie-Tooth disease.

Birouk N.

Service de neurophysiologie clinique, hôpital des spécialités, BP

6220 Rabat-Instituts, Maroc.

Charcot-Marie-Tooth (CMT) disease, also known as peroneal muscular

atrophy or hereditary motor and sensory neuropathy, 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 have been identified to date 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

neuropathy 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 are 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 part on the classification of the different

genetic forms and in part on the phenotypic particularities and the

frequency of the responsible genes in the population under study.