Charcot-Marie-Tooth Disease

Charcot-Marie-Tooth disease refers to a group of inherited peripheral neuropathies caused by various genetic mutations. It has a prevalence of 1:2500 people and is one of the most common inherited disorders. While the majority of mutations associated with CMT are autosomal dominant, CMT also displays X-linked and recessive inheritance, making it not only genetically heterogeneous but challenging to diagnose. Patients with CMT typically present with a phenotype of symmetric sensory loss, muscle atrophy, and weakness in distal limbs with additional features such as foot deformities, tripping, and falls. CMT can cause de-/dys-myelination or axonal loss pathologically. However, the severity of the disease is highly variable among patients with CMT, even between individuals within the same family. While certain subtypes of CMT are rare, mutations causal for these diseases have been invaluable in understanding the functions of their encoded proteins. These monogenic conditions have also brought opportunities for gene therapies. This article focuses on the clinical, genetic, pathological, and electrophysiological characteristics of various CMT subtypes. New advancements in the pathogenesis of CMT and how this translates into ongoing search for therapeutic targets and management will be discussed.