Axonal Charcot–Marie–Tooth disease

Abstract

Charcot–Marie–Tooth disease (CMT), a clinically and genetically heterogeneous inherited neuropathy, is common with an estimated prevalence of 1 in 2,500. The cardinal clinical features of CMT are distal wasting, weakness, and sensory loss with reduced tendon reflexes and variable foot deformity. Neurophysiology is the most useful tool to classify CMT clinically into the two major forms, CMT1 (median motor conduction velocity [MCV] 38 m/s), with a third form characterized by intermediate motor conduction values being increasingly recognized. In the last 15 years, there have been rapid advances in identifying the underlying genetic defects in CMT, initially in autosomal dominant (AD) CMT1 but also in recent years in AD CMT2 and autosomal recessive (AR) CMT. As AD CMT is more common than the AR or the x-linked forms except in specific ethnic groups, the identification of a 1.5 Mb duplication of chromosome 17 containing the peripheral myelin protein 22 gene as the predominant cause of AD CMT1 and accounting for …