Charcot Marie Tooth: a Common Hereditary Neurological Disorder

Charcot-Marie-Tooth disease (CMT) is a group of hereditary disorders. It is one of the most common inherited neurological disorders. CMT is classified as a peripheral neuropathy, meaning a disease that affects peripheral nerves (nerves that lie outside the brain and spinal cord). Charcot-Marie-Tooth disease (CMT) is also known as Hereditary Sensorimotor Neuropathy (HSMN), Hereditary Motor and Sensory Neuropathy (HMSN), or Peroneal Muscular Atrophy (PMA). According to the National Institute of Neurological Disorders and Stroke (NINDS) Charcot-Marie-Tooth disease affects 1 in 2,500 people in the United States.

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Symptoms of CMT disease usually appear in late childhood or early adulthood. Signs and symptoms include: weakness in the legs, ankles and feet, frequent falling, numbness and pain in legs, loss of muscle bulk in legs and feet, hammertoes (curled toes), high foot arches, decreased ability to walk and run, and footdrop (inability to lift foot at the ankle). Patients affected with CMT may experience weakness in the hands and forearms as the disease progresses. In some, breathing, hearing and vision can be affected, as can the neck and shoulders.

CMT has a genetic basis. It is caused by mutations in genes that code for proteins that are involved in the structure and/or function of peripheral nerve cell axons. Many different proteins are affected in patients with CMT disease and there are many types of CMT disorders, named CMT1, CMT2, CMT3, CMT4, and CMTX, CMT2, CMT3 and so on. These abnormal proteins generally bring about a slow, but steady degeneration of the myelin sheath that protects each nerve cell. This degeneration results in nerves losing their ability to communicate. The final result is muscle atrophy in the extremities and reduced ability to feel heat, cold, and pain.

Since CMT is a group of different inherited disorders there are many ways that this disease is passed form parents to children. Some forms of CMT (for example CMT1) are autosomal dominant (only one copy of the mutated gene is needed to cause the disease). Others are an autosomal recessive (both copies of the abnormal gene must be present to cause the disease) and some CMT forms are X-linked (the mutation is located on the X chromosome). Spontaneous mutation of genes involved in CMT is very rare.

There is currently no cure for Charcot-Marie-Tooth disease. Physical therapy, braces and orthopedic devices, can help patients cope with managing their disability. If there is severe pain, painkillers are prescribed. Research is ongoing to elucidate CMT causes and possible treatments. Two interesting areas of research on this disease are that of gene therapy (delivering correct versions of the mutated genes to nerve cells and muscles) and the use of nerve growth factors (androgen) to prevent nerve degeneration.

National Institute of Neurological Disorders and Stroke (NINDS). Charcot-Marie-Tooth Disease Fact Sheet.

Charcot-Marie-Tooth Disease. Mayo Clinic.com

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