Disease, Charcot-Marie-Tooth

A neuromuscular disease that is the most common inherited disorder of peripheral nerves, characterized by progressively debilitating weakness. The disease is also called peroneal muscular atrophy. The foremost feature of Charcot-Marie-Tooth disease (CMT) is marked wasting of the more distal extremities, particularly the peroneal muscle groups in the calves, resulting in "stork legs." CMT usually involves the legs before the arms. Pes cavus (deformity of the foot) is often the first sign of the disease. CMT affects about 1 in every 2-3,000 people and so is one of the most frequent genetic diseases. It is genetically heterogeneous (diverse); it can be inherited as an autosomal dominant, autosomal recessive, or X-linked trait; and there are also sporadic cases (with no family history of CMT) due to new dominant mutations. The disease is divided into two main types on the basis of the electrophysiology. Type 1 (CMT1) shows decreased motor nerve conduction velocities and primarily affects myelin (the substance that covers and protects nerves). Type 2 (CMT2) has normal (or only slightly reduced) motor nerve conduction velocities with decreased amplitudes and largely affects the axon (the nerve fiber that carries outgoing messages). CMT1 involves genes that encode proteins important to the formation, structure, and integrity of myelin. The first CMT2 gene to be identified, the gene NF-L, encodes neurofilament light protein, one of three major neurofilament protein constituents. (Neurofilaments are important for the structure and function of axons and may be necessary for axonal transport, regeneration, and longevity.) Physical therapy can help to delay somewhat the wasting of limbs seen in CMT. Jean Charcot (1825-1893) was a celebrated professor of neurology in Paris (and was Sigmund Freud's mentor). Pierre Marie (1853-1940) was similarly a famous French neurologist.