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| DiseaseID |
HGD42 |
| Genetic
Disorder |
Charcot-Marie-Tooth disease
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| Gene
Name |
MPZ gene |
| Description |
Charcot-Marie-Tooth disease is a progressive hereditary disorder that causes nerve damage (neuropathy). The damage in Charcot-Marie-Tooth disease occurs to your peripheral nerves or to the insulation covering your nerves (myelin sheath). The peripheral nerves are those outside of your central nervous system (brain and spinal cord). Charcot-Marie-Tooth disease most often affects the legs, arms, hands and feet. It generally results in muscle weakness and loss of muscle bulk. In some cases, it may cause a mild loss of sensation.
Named after the three physicians who first identified the disorder in 1886, Charcot-Marie-Tooth disease is a common neurological disorder. It affects about one in 3,300 people worldwide and occurs in all races and ethnic groups. Charcot-Marie-Tooth disease most often is discovered between midchildhood and age 30, but can develop at any age.
Each form of Charcot-Marie-Tooth disease has a different inheritance pattern, age of onset, signs and symptoms, severity, and progression. Other names for Charcot-Marie-Tooth disease include hereditary motor and sensory neuropathy and peroneal muscular atrophy.
Charcot-Marie-Tooth disease isn't life-threatening, and most people with the disorder lead active, productive lives. Treatments such as physical and occupational therapy often are effective in managing the signs and symptoms of Charcot-Marie-Tooth disease. Surgery may help with more severe effects of the disease.
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| Symptoms |
The signs and symptoms of Charcot-Marie-Tooth disease (CMT) may vary from mild to severe and tend to develop slowly, sometimes appearing to stabilize spontaneously. Early signs and symptoms of CMT may include:
Weakness in your lower legs, ankles and feet
Excessively high foot arches
Flat feet
Curled toes (hammertoes)
Difficulty lifting your foot at the ankle (footdrop)
Awkward or higher than normal step (gait)
Loss of sensation in your hands or feet
Frequent tripping or falling
As CMT progresses, signs and symptoms may worsen or change. Later signs and symptoms may include:
Weakness in your arms and hands
Numbness and pain in your lower legs and feet
Decreased sensitivity to heat and cold
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| Causes |
Charcot-Marie-Tooth disease (CMT) is an inherited genetic disease. A unique form of the disease develops depending on the particular gene mutation. Genes produce the proteins that are essential to functions of the body. In CMT, defective genes affect the proteins involved in the structure and function of your peripheral nerves or the myelin sheath. Deterioration of your peripheral nerves or the myelin sheath can send only weak signals to the muscles in your legs, arms, hands and feet, causing weakness and numbness.
CMT can be inherited in various ways:
X-linked. In X-linked inheritance, the genetic defect (mutation) is located on the X chromosome. X-linked diseases are passed from mother to son through one of the mother's genes in a pattern called X-linked recessive inheritance. A boy inherits an X chromosome from his mother and a Y chromosome from his father. The X-Y combination makes him male. A girl inherits two X chromosomes, one from her mother and one from her father. The X-X combination makes her female. Women who have a defective gene that causes a disorder are simply carriers and exhibit no signs or symptoms of the disease. The disease can skip a generation until another son inherits the defective gene on the X chromosome.
Autosomal dominant. When the genetic defect occurs on a chromosome other than X or Y, CMT affects males and females the same. Autosomal dominant inheritance of CMT results when one copy of the defective gene is enough to cause the disease. If either parent carries the defective gene for CMT, there's a 50 percent chance the disorder will be passed along to a child.
Autosomal recessive. Autosomal recessive inheritance occurs when two copies of the defective gene are required to cause CMT. One copy is inherited from each parent, neither actually having CMT.
Some types of CMT can pass from generation to generation and affect males and females equally. In other cases of CMT, the disease arises from a new or spontaneous mutation in a gene rather than from an inherited defective gene, meaning there's no previous family history of the disorder. |
| Diagnosis |
A careful review of your family's history of nerve disease can help your doctor reach a diagnosis. In addition to a medical history review and physical examination, your doctor may rely on the following tests to diagnose Charcot-Marie-Tooth disease (CMT):
Neurological examination. During a neurological examination, your doctor looks for signs of muscle weakness in your arms, legs, hands and feet, decreased muscle bulk, reduced reflexes, and sensory loss. He or she also will look for evidence of foot deformities, such as high arches and flat feet.
Nerve conduction studies. These tests measure the strength and speed of electrical signals transmitted through your nerves. Electrodes are placed on your skin over a peripheral or sensory nerve. The electrodes produce small electric shocks that stimulate the nerve. Delayed or weak responses may indicate a nerve disorder such as CMT. Applying a topical anesthetic may ease discomfort caused by the shocks.
Electromyography (EMG). A thin-needle electrode is inserted through your skin into the muscle to be tested. Electrical activity is measured as you relax and as you gently tighten the muscle. Changes in the pattern of electrical activity can confirm CMT. Your doctor may be able to determine the distribution of the disease by testing different muscles.
Nerve biopsy. A small piece of peripheral nerve is taken from the calf of your leg through an incision in your skin. Laboratory analysis of the nerve distinguishes CMT from other nerve diseases.
Genetic testing. These tests, which can detect the most common genetic defects known to cause CMT, are done by blood sample and can result in a definite diagnosis of some types of CMT. Genetic testing for CMT may improve diagnosis and give people with the disorder more information for family planning.
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| Treatment |
There's no cure for Charcot-Marie-Tooth disease (CMT). However, some treatments can help you manage its signs and symptoms, including:
Physical therapy. Physical therapy for CMT involves muscle strengthening and stretching to prevent muscle tightening and loss. A physical therapy program usually consists of low-impact exercises and stretching techniques guided by a trained physical therapist and approved by your doctor. Started early and followed regularly, physical therapy can play an important part in delaying nerve deterioration and muscle weakness before disability is present.
Occupational therapy. Some people with CMT may experience weakness in their arms and hands, causing difficulty with gripping and finger movement. Normal daily activities, such as fastening buttons or writing, can become difficult. Occupational therapy can help you deal with such challenges through the use of assistive devices, such as special rubber grips on doorknobs or clothing with snaps instead of buttons.
Orthopedic devices. Many people with CMT require the help of certain orthopedic devices to maintain everyday mobility and to prevent injury. Leg and ankle braces or splits can provide stability during walking and climbing stairs. Wearing boots or high-top shoes may provide additional ankle support. Custom-made shoes or shoe inserts may improve your gait. If you have hand weakness and difficulty with gripping and holding things, thumb splints may help.
Surgery. If the signs and symptoms of CMT become severe and other treatment methods don't help, surgery may be an option to reverse foot and joint deformities. Ankle surgery may stabilize the ankle or provide better distribution of weight. Foot surgery is discouraged if special footwear or supportive orthopedic devices can help instead.
Research continues to provide additional treatment options that might stop or reverse the effects of CMT. Studies are also under way to determine if CMT can be prevented. Future treatment may include the use of gene replacement therapy, which may involve delivering specific genes to certain cells and muscles, and using nerve growth factors, such as the hormone androgen, to prevent nerve deterioration caused by CMT. Other research includes treating CMT with stem cells. In recent laboratory experiments, scientists have found ways to turn stem cells into nerve cells and myelin-producing cells. It may be possible to use these cells to replace the damaged or diseased cells that cause CMT or to repair nerves damaged by the effects of the disease. |
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