- Charcot-Marie-Tooth disease
- A neuromuscular disease, the most common inherited disorder of peripheral nerves, characterized by progressively debilitating weakness. The disease is also called peroneal muscular atrophy and hereditary motor and sensory neuropathy. 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 1 in about every 2-3,000 people so it is one of the more frequent genetic diseases. The ways in which CMT is inherited are diverse. It is genetically highly heterogeneous. It can be inherited as an autosomal dominant trait, an autosomal recessive trait, and an 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 a number of types. The two main types on the basis of the electrophysiology are types 1 and 2. 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.) CMT4A involves a gene on chromosome 8 that encodes ganglioside-induced differentiation-associated protein-1 (GDAP1). How mutations in GDAP1 lead to CMT4A remains to be understood. 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 also a famous French neurologist. Howard Henry Tooth (1856-1925) was an English physician.
* * *Char·cot-Ma·rie-Tooth disease (.)shär-.kō-mə-.rē-'tüth- n PERONEAL MUSCULAR ATROPHY P. Marie see MARIE-STRÜMPELL DISEASETooth Howard Henry (1856-1925)British physician. Tooth enjoyed a varied career as a consulting physician to a British hospital for the paralyzed and epileptic, as an examiner in medicine at Cambridge and Durham universities, and as physician to British troops in Malta. In 1886 he published a description of peroneal muscular atrophy. In that same year an independent description of the disease was published jointly by Jean-Martin Charcot and Pierre Marie.
* * *a group of inherited diseases of the peripheral nerves, now more commonly known as hereditary sensorimotor neuropathy, causing a gradually progressive weakness and wasting of the muscles of the legs and the lower part of the thighs. The hands and arms are eventually affected. The genetic defect responsible for the most common form, type Ia, is a duplication on chromosome 17. This can be detected by a simple blood test.
* * *(CMT) a group of hereditary conditions characterized by chronic motor and sensory polyneuropathy, of variable inheritance and including autosomal dominant, autosomal recessive, and X-linked forms. It is divided into two major types on the basis of nerve conduction velocities (NCV), each with subtypes: CMT1 is a demyelinating polyneuropathy with symmetrically slowed NCV, onion bulb formation, and segmental demyelination; CMT2 is an axonal neuropathy, with normal NCV but of decreased amplitude, axonal loss visible on biopsy, and no onion bulb formation or segmental demyelination. Both are characterized by progressive symmetric distal muscle weakness and atrophy starting in the feet and legs, gait disturbance, and absent stretch reflexes. A variety of causative mutations have been identified at different loci, all concerned with myelin in Schwann cells, with the majority of cases of autosomal dominant CMT1 caused by duplication of chromosomal region 17p12, containing a gene encoding a peripheral myelin protein (PMP22). Called also Charcot-Marie atrophy or syndrome, and peroneal or peroneal muscular atrophy.
Medical dictionary. 2011.