Charcot-Marie-Tooth disease

• Charcot-Marie-Tooth disease (CMT), also called hereditary motor sensory neuropathy and peroneal muscular atrophy, is an inherited disorder that causes nerve damage, or neuropathy. This nerve damage worsens over time.
• The disease affects the myelin sheath, which is the fatty substance that insulates the nerves. Myelin is needed to transmit impulses along nerve cells. In CMT, genetic mutations cause the peripheral nerves to become damaged or the myelin to become dysfunctional, which makes the nerves vulnerable to damage.
• The disorder typically causes muscle weakness and sometimes numbness in the arms, legs, hands, and feet. Symptoms usually develop during adolescence or early adulthood, but they may occur at any time from early childhood into middle age.
• CMT is the most common neurological disorder, affecting about one in 3,300 people worldwide. It is estimated that 150,000 people in the United States have CMT.
• There are five main variations of CMT. Each type is caused by different genetic mutations, or abnormal changes in a person's biological makeup. Each is inherited, or passed down among families, in a different pattern. In addition, the age of onset, symptoms, severity, and progression of the disease varies, depending on the specific variation of CMT a person has.
• The most common form of CMT is called CMT1. People with CMT1 are born with abnormal genes that are involved in the development and function of the myelin sheath. These defective genes cause the breakdown of myelin called demyelination. When the protective myelin deteriorates, the peripheral nerves are exposed and are vulnerable to damage. Other, less common, forms include CMT2, CMT3, CMT4, and CMTX.
• Although this condition is not considered life-threatening, symptoms worsen over time. There is currently no cure for CMT, but treatments are available to help manage the symptoms of the disease. Physical and occupational therapy or surgery can help people with CMT to lead active, productive lives.

• Having a family history of Charcot-Marie-Tooth disease (CMT) increases the risk of inheriting the disorder.

• General: Charcot-Marie-Tooth disease (CMT) is a genetic disorder that is most often passed down from parents to their children. Many different genetic mutations have been shown to cause CMT. Genes provide the body with instructions on how to produce particular proteins needed for proper development and function. In people with CMT, the genes needed to produce proteins involved in the structure and function of the peripheral nerves or the myelin sheath contain mutations that cause the instructions to be carried out incorrectly. When these genes are mutated, the peripheral nerves become damaged or the myelin is unable to properly insulate the nerves, making them vulnerable to damage. As a result, only weak signals are sent to the muscles in the arms, legs, hands, and feet, causing symptoms of weakness and numbness.
• The genetic mutations that cause CMT may be inherited as X-linked dominant, autosomal recessive, or autosomal dominant traits. Some mutations occur randomly. In such cases, people may develop CMT even if they do not have family histories of the disorder.
• Autosomal recessive inheritance: Each gene has two variations, called alleles. One allele is inherited from each parent. CMT may be inherited as an autosomal recessive disorder. This means that two mutated alleles (one from each parent) of a single gene must be inherited in order for a person to have the disorder.
• People who have only one mutated allele are called carriers and usually do not experience symptoms. If one parent is a carrier, there is a 50% chance with each birth that a child will also be a carrier and a 0% chance that he or she will inherit the disease. If both parents are carriers, there is a 25% chance with each birth that the child will inherit the disease, a 50% chance with each birth that the child will be a carrier, and a 25% change with each birth that the child will inherit neither mutated gene.
• Autosomal dominant inheritance: Some cases of CMT are passed down as autosomal dominant traits. In such cases, people develop CMT if they inherit only one copy of the mutated gene from either of their parents. This means that if one parent has this form of CMT, there is a 50% chance with each birth that the child will have CMT. If both parents have this form of CMT, there is a 75% chance with each birth that the child will inherit the condition.
• X-linked-dominant inheritance: Some cases of CMT are passed down as X-linked dominant traits. Patients with this form of the disease have a mutation on the connexin-32 gene on the X chromosome. Because males have only one X chromosome, they tend to have more severe symptoms of the disease than females.
• Females, on the other hand, usually have milder symptoms. This is because females have two copies of the X chromosome. Most females with X-linked CMT have one normal X chromosome and one mutated X chromosome. As a result, they usually have mild symptoms that develop during adolescence or later in life. Some may not develop any symptoms at all.
• Random occurrence: Some cases of CMT are not inherited. Instead, they occur when a genetic mutation randomly occurs during the development of the egg, sperm, or embryo.

• General: Symptoms of Charcot-Marie-Tooth disease (CMT) vary from mild to severe. In general, symptoms tend to progress slowly over time.
• Early symptoms: Symptoms typically develop during adolescence or early adulthood, but they may occur anytime from early childhood to mid-adulthood. Early symptoms may include weakness in the lower legs and feet, flat feet or excessively high foot arches, curled toes (called hammertoes), awkward or higher-than-normal step, difficulty lifting the foot at the ankle (called footdrop), loss of sensation in the hands or feet, and frequent falling.
• More advanced symptoms: The condition gradually worsens over time. More advanced symptoms may include weakness in the arms and hands, numbness and pain in the lower legs and feet, and
  decreased sensitivity to hot and cold temperatures.

• General: If Charcot-Marie-Tooth disease (CMT) is suspected, several different tests may be performed to confirm a diagnosis.
• Neurological examination: During a neurological examination, a doctor looks for signs of muscle weakness, particularly in the arms, legs, hands, and feet. In addition, signs of reduced muscle bulk, decreased sensation, and reduced reflexes may indicate a nerve disorder such as CMT. Physical deformities in the feet, such as excessively high arches or flat feet, footdrop, or curled toes, may also indicate CMT.
• Electrodiagnostic tests: If CMT is suspected, electrodiagnostic tests may be performed. This type of testing involves nerve conduction studies and electromyography (EMG). During nerve conduction studies, electrodes are placed on the skin. The electrodes deliver a mild electrical shock to measure the speed and strength of electrical signals that are transmitted by the patient's nerves.
• An EMG involves inserting a needle electrode through the skin to measure the electrical activity of the person's muscles when he or she relaxes and tightens them. Abnormalities in the pattern of electrical activity can confirm CMT. If CMT is confirmed, a doctor may test different muscles to determine which parts of the body are affected by the disorder.
• Nerve biopsy: If it is clear that a person has a nerve disorder, a nerve biopsy may be performed to distinguish CMT from other nerve diseases. During the procedure, a small piece of peripheral nerve is taken from the calf of the leg. The sample is then analyzed under a microscope. If the patient has CMT1, signs of abnormal myelination are usually found. If the patient has CMT2, signs of axon degeneration are usually found.
• Genetic testing: Genetic testing may also be performed to confirm a diagnosis of some of the most common types of CMT. A small sample of the patient's blood is taken and analyzed for the presence of genetic mutations known to cause certain types of CMT. If a person has a family history of CMT, prenatal genetic testing may be performed. However, there are serious risks associated with prenatal diagnostic testing, including miscarriage. Therefore, people should discuss the potential risks and benefits of prenatal testing before making any health-related decisions. Genetic testing may also be performed to determine whether a person is a carrier of some forms of CMT.

• Difficulty walking or performing everyday tasks: Charcot-Marie-Tooth disease (CMT) causes muscle weakness and decreases sensation in the muscles and feet. As a result, patients often have trouble controlling foot movements, and the most common complication of CMT is difficulty walking. Some people may have trouble performing daily activities. For instance, if the arms and hands feel numb and weak, it may be difficult to use eating utensils or get dressed.
• Injury to affected areas: Because CMT leads to decreased sensations, particularly in the hands and feet, people have an increased risk of unknowingly injuring these parts of the body. For example, if a blister develops on the foot, a person with CMT may not notice the sore. The sore may worsen or even become infected if it does not cause noticeable pain.

• General: Charcot-Marie-Tooth disease (CMT) is not life-threatening, but there is currently no known cure and symptoms slowly worsen over time. Treatments are available to help manage the symptoms of the disease, and many people are able to lead active, productive lives.
• Physical therapy: People with CMT often undergo physical therapy in order to strengthen and stretch the muscles. People meet with qualified physical therapists one or more times per week. A variety of techniques, including low-impact exercises, stretches, traction, electrical stimulation, and massage, are used during physical therapy sessions. Physical therapy may help slow nerve deterioration and muscle weakness.
• Occupational therapy: As CMT worsens, some people may have difficulty performing daily activities. For instance, if the arms and hands feel numb and weak, it may be difficult to use eating utensils or to get dressed. Occupational therapy may help people learn how to overcome daily challenges with the use of assistive devices, such as canes, rubber grips on doorknobs, or shoes that fasten with Velcro® instead of shoelaces.
• Stretching: People with CMT are encouraged to stretch their muscles regularly. A physical or occupational therapist may teach patients specific types of stretches to perform at home. This helps improve flexibility, coordination, and balance. It may also help reduce the risk of injury. In addition, stretching may help reduce joint deformities, such as high arches, hammertoes, inverted heels, or flat feet, which may be caused by the uneven pulling of muscles on the bones.
• Regular exercise: People are encouraged to exercise regularly in order to keep the muscles and bones strong. Low-impact exercises, such as swimming and cycling are generally recommended in people with CMT. Strengthening the body may help improve balance and coordination.
• Orthopedic devices: Orthopedic devices may help people with CMT maintain mobility and prevent injuries. For example, leg braces or splints may provide stability when a person walks or climb stairs. High-top shoes may provide extra ankle support and help reduce the risk of falling. A cane or walker may help people with weak or numb legs walk. People should talk to their doctors to determine the best orthopedic devices for their needs.
• Surgery: In severe cases, surgery may be recommended to fix foot and joint deformities caused by CMT. Ankle surgery may help stabilize the joint or help provide better distribution of weight. Surgical procedures vary depending on the specific type and severity of physical abnormality. Foot surgery is generally performed only if other therapies and orthopedic devices have not been helpful.
• Potential future treatments: Researchers are investigating newer therapies for CMT. In the future, it may be possible to use gene therapy in CMT patients. Gene therapy is an experimental procedure that involves inserting human genes into a patient in order to treat or prevent an illness. In general, gene therapy is being studied as a possible way to either replace or inactivate mutated genes associated with particular disorders. Other gene therapy studies involve inserting a new gene to help the body fight against a specific disease.
• It has been suggested that delivering specific genes into certain cells (called Schwann cells) and muscles, and using nerve growth factors, such as the hormone androgen, may help prevent nerve deterioration caused by CMT. Although early research is promising, additional research in humans is needed to determine whether gene therapy is a safe and effective treatment.
• Other scientists are studying stem cells as a possible treatment for CMT. These are unspecialized cells that have the potential to develop into different types of specialized cells. They are present in many body tissues, such as the brain and liver, umbilical cord, and the embryo. In laboratory studies, researchers have found ways to turn stem cells into nerve cells and myelin-producing cells.

Note
: Currently, there is a lack of scientific data on the use of integrative therapies for the treatment or prevention of Charcot-Marie-Tooth disease (CMT). However, some therapies have been studied as possible treatments for peripheral neuropathy in general. The integrative therapies listed below should be used only under the supervision of a qualified healthcare provider and should not be used in replacement of other proven therapies.

C

Unclear or conflicting scientific evidence

• L-carnitine
  : The human body produces L-carnitine in the liver, kidneys, and brain. Based on early studies, it is unclear if L-carnitine can effectively treat peripheral neuropathy. Additional research is warranted in this area.
• Avoid if allergic to L-carnitine. Use cautiously with peripheral vascular disease, high blood pressure, alcohol-induced liver cirrhosis, or diabetes. Use cautiously in low birth weight infants and individuals on hemodialysis. Use cautiously if taking anticoagulants (blood thinners), beta-blockers, or calcium channel blockers. Avoid if pregnant or breastfeeding.
• TENS
  : Transcutaneous electrical nerve stimulation (TENS) is a non-invasive technique in which a low-voltage electrical current is delivered through wires from a small power unit to electrodes located on the skin. TENS is often used as an alternative or in addition to pain medications. Several case reports and a small number of controlled trials report improvements in pain symptoms in people with peripheral neuropathy or nerve damage. These studies have not been well designed or reported, however, and additional research is needed before a firm conclusion can be drawn about effectiveness.
• Avoid with implantable devices, such as defibrillators, pacemakers, intravenous infusion pumps, or hepatic artery infusion pumps. Use cautiously with decreased sensation, such as neuropathy, and with seizure disorders. Avoid if pregnant or breastfeeding.

• There is currently no known method of preventing Charcot-Marie-Tooth disease (CMT). If a person has a family history of the disorder he or she may undergo genetic testing to determine if he or she carries a mutated gene associated with the disorder. However, genetic testing is available only for the most common forms of CMT.
• People who are diagnosed with CMT can practice self-care techniques to reduce the risk of developing complications of the disorder. For example, people with CMT are encouraged to stretch their muscles regularly. This helps improve flexibility, coordination, and balance. It may also help reduce the risk of injury or joint deformities caused by the uneven pulling of muscles on the bones. Regular exercise may also help keep the muscles and bones strong and improve a person's balance and coordination.
• Orthopedic devices may help people with CMT maintain mobility and prevent injuries. For example, leg braces or splints may provide stability when a person walks or climbs stairs. High-top shoes may provide extra ankle support and help reduce the risk of falling. A cane or walker may help people with weak or numb legs walk. People should talk to their doctors to determine the best orthopedic devices for their needs.