Genetics of Charcot-Marie-Tooth disease

Abstract

Charcot-Marie-Tooth disease (CMT) is a group of genetic peripheral neuropathies which is associated with a broad variety of clinical and genetic features. Most CMT syndromes are characterised by a combination of progressive muscle weakness and atrophy with a distally pronounced sensory dysfunction. Bone deformities like pes cavus or hammer toes are frequently associated symptoms. However, the muscular impairment is the most prominent clinical sign. The severity of disability varies according to the different subclasses. It is well known that even in the same subclass of CMT syndrome the phenotypic expression of the disease is heterogeneous. Ten different candidate genes have been identified for different CMT syndromes. Electrophysiological and histological findings build the outer frame for the classification while the distinction into several subgroups is made on the basis of the underlying genetic alteration. Although no therapeutic strategies have been developed so far, genetic testing is available for the most frequent forms of Charcot-Marie-Tooth disease.