Charcot disease

Definition

Charcot-Marie-Tooth disease (CMT) is the name for a group of inherited disorders of nerve conduction causing weakness and mild loss of sensation in the limbs.

Description

CMT affects the peripheral nerves, those groups of nerve cells carrying information to and from the spinal cord. CMT decreases the ability of these nerves to carry motor commands to muscles, especially those furthest from the spinal cord in the feet and hands. As a result, these muscles are weakened. CMT also causes mild sensory loss.

CMT is named for the three neurologists who first described it, and does not involve the teeth in any way. It is also known as hereditary motor and sensory neuropathy, and is also sometimes called peroneal muscular atrophy, referring to the muscles in the leg affected early on in the disease.

Causes & symptoms

Causes

The symptoms grouped together under the name CMT can be caused by any of at least six different genetic defects. Most of the defects, identified as of early 1998, affect myelin, the coating that insulates nerve cells to promote efficient conduction. Myelin defects cause either a reduction in nerve conduction velocities, or a diminished nerve signal.

CMT is currently subdivided into type 1A, type 1B, type 2, and type X, based on the particular genetic defect involved. All but type X exhibit the inheritance pattern known as autosomal dominant. In this pattern, only one defective gene copy is needed to develop the disease, which may be inherited from either parent (who will also have the disease). A person with CMT of this type has a 50% chance of passing the gene along to each offspring. CMT type X is inherited as an X-linked trait, meaning the gene is carried on the X chromosome. Women carry two X chromosomes, while men carry only one. Without a "backup" copy of the normal gene, a man with the CMT type X gene is more likely to be seriously affected than is a woman. Expression of the gene does occur in women to a lesser extent, leading to disease of variable severity. Affected men may pass the gene on to their daughters, but not to their sons.

A rare, related disorder, called CMT type 3 or Dejerine-Sottas disease, also involves myelin. It is an autosomal recessive trait, meaning genetic contributions from both parents are needed for a child to express the disease.

Symptoms

CMT causes progressive, symmetrical weakness and muscle atrophy, or wasting. The earliest symptoms include foot deformity and difficulty walking or running. The characteristic deformities of CMT are very high arches and flexed toes, or "claw-toe." Foot deformities may lead to pain in poorly-fitted shoes. Foot drop may lead to tripping or require deliberate high steps over curbs and other obstructions. Sports involvement may lead to frequent sprains or fractures of the ankles. Symptom onset in type 1 is usually in childhood or adolescence, while for type 2 it may be in the early twenties or later.

Symptoms progress from the feet upward to the calves then thighs, and from leg weakness only to involve the fingers and hands. There may be minor loss of sensation in the feet and hands as well, although this rarely causes difficulty. Complaints of cold legs are common, as are cramps in the legs, especially after exercise. Some patients develop tremor in the upper limbs as the disease progresses. Most people with CMT remain able to walk throughout their lives.

Diagnosis

Diagnosis of CMT begins with a careful medical history and a detailed neurological exam to determine the extent and distribution of weakness. A nerve conduction velocity test, an electrical test of nerve function, shows characteristic changes. This is often combined with electromyography, an electrical test of the muscles. A nerve biopsy--removal of a small piece of the nerve--may be performed to look for the swelling characteristic of CMT type 1. DNA testing is available for CMT type 1, but not for other types currently. DNA testing may be performed on both the person suspected of having CMT and on family members who may be at risk.

Treatment

Physical and occupational therapy form an important part of CMT treatment. Physical therapy is used to preserve range of motion and minimize deformity caused by muscle shortening, or contracture. Braces are sometimes used to improve control of the lower extremities. Occupational therapy is used to design compensatory tools and techniques to aid in dressing, feeding, writing, and other activities of daily living.

Tremors may be worsened by caffeine, so reducing caffeine use may help minimize them. Beta-blockers may help relieve tremor. Alcohol should be avoided, as should certain drug combinations that can cause muscle damage. Such damage may result from combining gemfibrozil (Lopid) with lovastatin (Mevacor), for instance, both used to treat high cholesterol levels.

Prognosis

CMT causes progressive weakness, but does not usually shorten life expectancy. Most people with CMT are able to lead full and productive lives despite their impairments.

Prevention

There is no way to prevent CMT in a person who has the gene or genes responsible. Genetic testing is available for family planning purposes.

Key Terms

Neuropathy

A disorder of the nerves.

Peripheral nerves

Nerves that carry information to and from the spinal cord.

Further Reading

For Your Information

Books

• James, P., M.D. Dyck, and M.D. Thomas, eds.Peripheral Neuropathy. 3rd ed. Philadelphia: W. B. Saunders, 1993.

  Periodicals

• Quest. Available from the Muscular Dystrophy Association.

  Organizations

• Muscular Dystrophy Association. 3300 East Sunrise Drive, Tucson, AZ 85718. (520) 529-2000. (800) 572-1717. Internet: http://www.mdausa.org

Gale Encyclopedia of Medicine. Gale Research, 1999.