Causes of CMT, Charcot-Marie-Tooth Disease

Causes of Charcot-Marie-Tooth Disease
A nerve cell communicates information to distant targets by sending electrical signals down a long, thin part of the cell called the axon. In order to increase the speed at which these electrical signals travel, the axon is insulated by myelin, which is produced by another type of cell called the Schwann cell. Myelin twists around the axon like a jelly-roll cake and prevents the loss of  electrical signals. Without an intact axon and myelin sheath, peripheral nerve cells are unable to activate target muscles or relay sensory information from the limbs back to the brain.

CMT 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 CMT disease are usually inherited. Each of us normally possesses two copies of every gene, one inherited from each parent. Some forms of CMT 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 CMT 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 CMT 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.

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