What is Charcot-Marie-Tooth disease?

Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neurological disorders, affecting approximately 1 in 2,500 people in the United States. The disease is named for the three physicians who first identified it in 1886 – Jean-Martin Charcot and Pierre Marie in Paris, France, and Howard Henry Tooth in Cambridge, England.

Charcot-Marie-Tooth, also known as hereditary motor and sensory neuropathy or peroneal muscular atrophy, comprises a group of disorders that affect peripheral nerves. The peripheral nerves lie outside the brain and spinal cord and supply the muscles and sensory organs in the limbs. Disorders that affect the peripheral nerves are called peripheral neuropathies.

What are the symptoms of Charcot-Marie-Tooth disease?

Symptoms of Charcot-Marie-Tooth affects both motor and sensory nerves. A typical feature includes:

  1. Weakness of the foot and lower leg muscles, which may result in foot drop and a high-stepped gait with frequent tripping or falls.

  2. Foot deformities, such as high arches and hammertoes are also characteristic due to weakness of the small muscles in the feet.

  3. The lower legs may take on an “inverted champagne bottle” appearance due to the loss of muscle bulk.

  4. Later in the disease, weakness and muscle atrophy may occur in the hands, resulting in difficulty with fine motor skills.

Onset of symptoms is most often in adolescence or early adulthood, however presentation may be delayed until mid-adulthood. The severity of symptoms is quite variable in different patients and even among family members with the disease. Progression of symptoms is gradual. Pain can range from mild to severe, and some patients may need to rely on foot or leg braces or other orthopedic devices to maintain mobility. Although in rare cases patients may have respiratory muscle weakness, Charcot-Marie-Tooth is not considered a fatal disease and people with most forms of Charcot-Marie-Tooth have a normal life expectancy.

What causes Charcot-Marie-Tooth disease?

Charcot-Marie-Tooth is caused by mutations in genes that produce proteins involved in the structure and function of either the peripheral nerve axon or the myelin sheath. Although different proteins are abnormal in different forms of CMT disease, all of the mutations affect the normal function of the peripheral nerves. Consequently, these nerves slowly degenerate and lose the ability to communicate with their distant targets. The degeneration of motor nerves results in muscle weakness and atrophy in the extremities (arms, legs, hands, or feet), and in some cases the degeneration of sensory nerves results in a reduced ability to feel heat, cold, and pain.

The gene mutations in Charcot-Marie-Tooth disease are usually inherited. Each of us normally possesses two copies of every gene, one inherited from each parent. Some forms of Charcot-Marie-Tooth are inherited in an autosomal dominant fashion, which means that only one copy of the abnormal gene is needed to cause the disease. Other forms of Charcot-Marie-Tooth are inherited in an autosomal recessive fashion, which means that both copies of the abnormal gene must be present to cause the disease. Still other forms of Charcot-Marie-Tooth are inherited in an X-linked fashion, which means that the abnormal gene is located on the X chromosome. The X and Y chromosomes determine an individual’s sex. Individuals with two X chromosomes are female and individuals with one X and one Y chromosome are male. In rare cases the gene mutation causing Charcot-Marie-Tooth disease is a new mutation which occurs spontaneously in the patient’s genetic material and has not been passed down through the family.

How is Charcot-Marie-Tooth disease treated?

There is no cure for Charcot-Marie-Tooth, but

  • Physical therapy & Occupational therapy: 
    • Physical and occupational therapy, the preferred treatment for Charcot-Marie-Tooth, involves muscle strength training, muscle and ligament stretching, stamina training, and moderate aerobic exercise. Most doctors recommend a specialized treatment program designed to fit individual abilities and needs. It is also suggested entering into a treatment program early; muscle strengthening may delay or reduce muscle atrophy, so strength training is most useful if it begins before nerve degeneration and muscle weakness progress to the point of disability.
    • Stretching may prevent or reduce joint deformities that result from uneven muscle pull on bones. Exercises to help build stamina or increase endurance will help prevent the fatigue that results from performing everyday activities that require strength and mobility. Moderate aerobic activity can help to maintain cardiovascular fitness and overall health.  Low-impact or no-impact exercises, such as biking or swimming, rather than activities such as walking or jogging, which may put stress on fragile muscles and joints.
  • Braces and other orthopedic devices:
    • Many Charcot-Marie-Tooth patients require ankle braces and other orthopedic devices to maintain everyday mobility and prevent injury. Ankle braces can help prevent ankle sprains by providing support and stability during activities such as walking or climbing stairs. High-top shoes or boots can also give the patient support for weak ankles. Thumb splints can help with hand weakness and loss of fine motor skills. Assistive devices should be used before disability sets in because the devices may prevent muscle strain and reduce muscle weakening.
  • Even surgery can help patients cope with the disabling symptoms of the disease & reverse foot and joint deformities.
  • In addition, pain-killing medications can be prescribed for patients who have severe pain.

What research is being done?

The National Institute of Neurological Disorders and Stroke (NINDS) supports research on Charcot-Marie-Tooth and other peripheral neuropathies in an effort to learn how to better treat, prevent, and even cure these disorders. Ongoing research includes efforts to identify more of the mutant genes and proteins that cause the various disease subtypes, efforts to discover the mechanisms of nerve degeneration and muscle atrophy with the hope of developing interventions to stop or slow down these debilitating processes, and efforts to find therapies to reverse nerve degeneration and muscle atrophy.

One promising area of research involves gene therapy experiments. Research with cell cultures and animal models has shown that it is possible to deliver genes to Schwann cells and muscle. Another area of research involves the use of trophic factors or nerve growth factors, such as the hormone androgen, to prevent nerve degeneration.

Where can I get more information?

For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute’s Brain Resources and Information Network (BRAIN) at:

BRAIN
P.O. Box 5801
Bethesda, MD 20824
(800) 352-9424
http://www.ninds.nih.gov

Information also is available from the following organizations:

Charcot-Marie-Tooth Association (CMTA)
2700 Chestnut Parkway
Chester, PA   19013-4867
info@charcot-marie-tooth.org
http://www.charcot-marie-tooth.org
Tel: 610-499-9264 800-606-CMTA (2682)
Fax: 610-499-9267

Muscular Dystrophy Association
3300 East Sunrise Drive
Tucson, AZ   85718-3208
mda@mdausa.org
http://www.mda.org
Tel: 520-529-2000 800-572-1717
Fax: 520-529-5300

Neuropathy Association
60 East 42nd Street
Suite 942
New York, NY   10165-0999
info@neuropathy.org
http://www.neuropathy.org
Tel: 888-PN-FACTS (888-763-2287)
Fax: 212-692-0668

National Ataxia Foundation (NAF)
2600 Fernbrook Lane North
Suite 119
Minneapolis, MN   55447-4752
naf@ataxia.org
http://www.ataxia.org
Tel: 763-553-0020
Fax: 763-553-016

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