Charcot-Marie-Tooth, or CMT, is the most commonly inherited peripheral neuropathy and is found worldwide among all races and ethnic groups. Discovered in 1886 by three physicians, Jean-Martin Charcot, Pierre Marie, and Howard Henry Tooth, CMT affects an estimated 2.6 million people.
Charcot Marie Tooth disease is a group of disorders in which the motor and/or sensory peripheral nerves are affected, resulting in muscle weakness and atrophy, as well as sensory loss. These manifestions occur first in the distal legs and later in the hands. The nerve cells in individuals with this disorder are not able to send electrical signals properly because of abnormalities in the nerve axon or abnormalities in the insulation (myelin) around the axon. Specific gene mutations are responsible for the abnormal function of the peripheral nerves. Charcot Marie Tooth disease can be inherited in an autosomal dominant, autosomal recessive or X-linked mode of inheritance.
Symptoms of CMT usually begin in late childhood or early adulthood. Some people do not experience symptoms until their early thirties or forties. Usually, the initial symptom is foot drop early in the course of the disease. This can also cause claw toe, where the toes are always curled. Wasting of muscle tissue of the lower parts of the legs may give rise to a “stork leg” or “inverted bottle” appearance. Weakness in the hands and forearms occurs in many people later in life as the disease progresses.
- foot drop
- claw toe
- wasting of muscle tissue of the lower parts of the legs
- weakness in the hands and forearms
- loss of touch sensation
- spasmodic muscular contractions
- breathing, hearing, vision can be affected
Loss of touch sensation in the feet, ankles and legs, as well as in the hands, wrists and arms is characteristic in various types of the disease. Early and late onset forms occur with ‘on and off’ painful spasmodic muscular contractions that can be disabling when the disease activates. High arched feet (pes cavus) are classically associated with the disorder. Sensory and proprioceptive nerves in the hands and feet are often damaged, while pain nerves are left intact. Overuse of an affected hand or limb can activate symptoms including numbness, spasm, and painful cramping.
Symptoms and progression of the disease can vary. Breathing can be affected in some; so can hearing, vision, as well as the neck and shoulder muscles. Scoliosis is common. Hip sockets can be malformed. Gastrointestinal problems can be part of CMT, as can chewing, swallowing, and speaking (due to atrophy of vocal cords). A tremor can develop as muscles waste. Pregnancy has been known to exacerbate CMT, as well as extreme emotional stress. Patients with CMT must avoid periods of prolonged immobility such as when recovering from a secondary injury as prolonged periods of limited mobility can drastically accelerate symptoms of CMT.
Neuropathic pain is often a symptom of CMT, though, like other symptoms of CMT, its presence and severity varies from case to case. For some people, pain can be significant to severe and interfere with daily life activities. However, pain is not experienced by all people with CMT. When pain is present as a symptom of CMT, it is comparable to that seen in other peripheral neuropathies, as well as Postherpetic neuralgia and Complex regional pain syndrome, among other diseases
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Although there is no current standard treatment, the use of ascorbic acid has been proposed, and has shown some benefit in animal models. A clinical trial to determine the effectiveness of high doses of ascorbic acid (vitamin C) in treating humans with CMT type 1A has been conducted. The results of the trial upon children have shown that a high dosage intake of ascorbic acid is safe but the efficacy endpoints expected were not met. In 2010, a study published in the Journal Science indicated that scientists had identified those proteins that control the thickness of myelin sheath. This discovery is expected to open the avenue to new treatments in the coming years.
The most important activity for patients with CMT is to maintain what movement, muscle strength, and flexibility they have. Therefore, physical therapy and moderate activity are recommended but overexertion should be avoided. A physiotherapist should be involved in designing an exercise program that fits a patient’s personal strengths and flexibility. Bracing can also be used to correct problems caused by CMT. Gait abnormalities can be corrected by the use of either articulated (hinged) or unarticulated, braces called AFOs (ankle-foot orthoses). These braces help control foot drop and ankle instability and often provide a better sense of balance for patients. Appropriate footwear is also very important for people with CMT, but they often have difficulty finding well-fitting shoes because of their high arched feet and hammer toes. Due to the lack of good sensory reception in the feet, CMT patients may also need to see a podiatrist for help in trimming nails or removing calluses that develop on the pads of the feet. A final decision a patient can make is to have surgery. Using a podiatrist or an orthopedic surgeon, patients can choose to stabilize their feet or correct progressive problems. These procedures include straightening and pinning the toes, lowering the arch, and sometimes, fusing the ankle joint to provide stability. CMT patients must take extra care to avoid falling because fractures take longer to heal in someone with an underlying disease process. Additionally, the resulting inactivity may cause the CMT to worsen.
The Charcot-Marie-Tooth Association classifies the chemotherapy drug vincristine as a “definite high risk” and states that “vincristine has been proven hazardous and should be avoided by all CMT patients, including those with no symptoms.”