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Definition of Charcot-Marie-Tooth (CMT) Disease
Charcot-Marie-Tooth (CMT) disease – An inherited neuromuscular disorder in which the myelin sheath that covers and protects the peripheral nerves deteriorates. The loss of the myelin sheath allows nerve signals to escape from the nerves before they reach their destinations.
CMT is the most common inherited neuromuscular disorder in the United States, affecting about 150,000 Americans. CMT is slowly progressive though not fatal, with symptoms typically beginning in late adolescence or early adulthood.
There are numerous forms of CMT, each arising from mutation of different genes that encode the proteins that form the myelin sheath.
The most common is CMT1, which occurs in three autosomal dominant variations that cause abnormal structure in the myelin sheath:
- CMT1A results when the person inherits an extra copy of the gene on chromosome 17 that encodes peripheral myelin protein 22 (PMP-22), causing excessive production of PMP-22.
- CMT1B occurs as a result of mutations to the gene that encodes myelin protein 0 (MP-0).
- CMT1C results from mutations to genes that encode for other peripheral myelin proteins, though researchers have not yet identified the mutations.
Other forms of Charcot-Marie-Tooth (CMT) disease include:
- CMT2, in which there are defects in the axons of the peripheral nerves rather than in the structure of the myelin sheath
- CMT3, also called Dejerine-Sottas disease, which results from mutations to the MP-0 or PMP-22 gene and causes severe symptoms beginning in the first year of life
- CMT4, in which various gene mutations cause symptoms that begin in childhood and progress to complete loss of motor function of the lower extremities by adolescence
- CMTX, which arises from a mutation in the connexin 32 gene on the X chromosome and causes more severe symptoms in males
Occasionally CMT occurs as a spontaneous mutation, without family history of the disease, and may affect any of the genes that encode for myelin proteins.
Symptoms and Diagnostic Path
Symptoms affect primarily the legs and feet in most forms of Charcot-Marie-Tooth (CMT), though in some forms may also affect the arms and hands. Though the motor symptoms of CMT are most prominent, CMT also affects sensory perceptions and can cause tingling and numbness (paresthesia). Characteristic symptoms of CMT include
- Apparent clumsiness or difficulty walking, running, and jumping
- Progressive weakness in the legs and feet, and occasionally in the arms and hands
- Atrophy (wasting) of MUSCLE mass in the affected extremities
- Diminished sensory perception in the extremities, particularly of heat, cold, and PAIN
- Foot drop and heel slap when walking, indications of muscle weakness in the lower leg and foot
The diagnostic path includes a comprehensive neurologic examination, detailed personal health history, nerve conduction studies, and electromyogram (EMG). The neurologist may also perform a nerve biopsy to examine the structure of nerve cells in the muscle tissue and genetic testing for mutations known to cause CMT.
The neurologic examination typically shows diminished or absent reflexes at the elbow, knee, and ACHILLES TENDON.
Treatment Options and Outlook
CMT is a progressive, lifelong condition. Symptoms in CMT1 generally stop short of complete loss of motor function in the affected extremities. Other forms of CMT, notably CMT4 and CMTX, may result in inability to walk.
Physical therapy and daily physical activity—strength exercise, resistance exercise, and activities to improve balance and flexibility such as yoga—can extend unassisted mobility. Bicycling and swimming are excellent activities for aerobic exercise as well as for strengthening and flexibility with minimal impact on the ankles, which are the most vulnerable as CMT progresses.
Adaptive devices such as braces, walkers, and wheelchairs can aid mobility when motor function deteriorates to a point that cannot support independent mobility. Some people benefit from surgery to rebalance muscles and tendons, in particular to provide support for the feet.
Despite the progressive nature of CMT, the condition is not fatal; and with adaptive devices and environmental modifications, most people who have CMT can enjoy productive lifestyles.
Risk Factors and Preventive Measures
CMT is nearly always an inherited condition, so the key risk factor is genetics. Genetic counseling can assist couples with family planning. Early diagnosis and treatment preserves muscle strength and function to the greatest extent possible.
High-top shoes and braces to support the ankle extend mobility and reduce the risk for ankle injuries such as sprains, strains, and fractures.
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