$Unique_ID{BRK03587} $Pretitle{} $Title{Charcot-Marie-Tooth Disease} $Subject{Charcot-Marie-Tooth Disease Peroneal Muscular Atrophy CMT Hereditary Sensory Motor Neuropathy HSMN Dejerine-Sottas Disease Hereditary Sensory Radicular Neuropathy Refsum Syndrome Familial Amyloid Neuropathy} $Volume{} $Log{} Copyright (C) 1986, 1987, 1988, 1989, 1991 National Organization for Rare Disorders, Inc. 261: Charcot-Marie-Tooth Disease ** IMPORTANT ** It is possible the main title of the article (Charcot-Marie-Tooth Disease) is not the name you expected. Please check the SYNONYMS listing to find the alternate names and disorder subdivisions covered by this article. Synonyms Peroneal Muscular Atrophy CMT Hereditary Sensory Motor Neuropathy HSMN Information on the following diseases can be found in the Related Disorders section of this report. Dejerine-Sottas Disease Hereditary Sensory Radicular Neuropathy Refsum Syndrome Familial Amyloid Neuropathy General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Charcot-Marie-Tooth disease is a hereditary neurological disorder, characterized by weakness and atrophy, primarily in the legs. Disappearance of the fatty shield surrounding the nerves (segmental demyelination) of peripheral nerves and associated degeneration of part of the nerve cells (axons) characterize this disorder. Symptoms Symptoms of Charcot-Marie-Tooth disease usually begin gradually sometime between middle childhood and age 30. Muscle atrophy and weakness are most prominent in the legs and the small muscles of the hands. The most incapacitating symptom of CMT is "foot drop", producing a slapping gait. Pain and unusual sensations (paresthesias) rarely may be present in the affected limbs. A decrease in vibration, pain and thermal sensation in the hand, foot and lower part of the leg (glove and stocking pattern) is common. Stretch reflexes are usually absent. The disease is slowly progressive, but may arrest spontaneously. Patients may remain active for years and live a normal life span. Causes CMT disease is usually inherited through an autosomal dominant transmission. It may also be inherited through a recessive hereditary mechanism or sex-linked recessive inheritance. Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the normal gene and resulting in appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child. In recessive disorders, the condition does not appear unless a person inherits the same defective gene from each parent. If one receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will show no symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is twenty-five percent. Fifty percent of their children will be carriers, but healthy as described above. Twenty-five percent of their children will receive both normal genes, one from each parent and will be genetically normal. X-linked recessive disorders are conditions which are coded on the X chromosome. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. Therefore in females, disease traits on the X chromosome can be masked by the normal gene on the other X chromosome. Since males have only one X chromosome, if they inherit a gene for a disease present on the X, it will be expressed. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. Women who are carriers of an X-linked disorder have a fifty percent risk of transmitting the carrier condition to their daughters, and a fifty percent risk of transmitting the disease to their sons. Affected Population Onset of CMT disease is usually between middle childhood and age 30. It affects an equal number of males and females. CMT occurs worldwide at a rate of 1 in 2,500. Approximately 125,000 Americans have CMT. Related Disorders Dejerine-Sottas disease (Hypertrophic Interstitial Neuropathy) is a rare disorder in which proliferation of the cells of the membrane around certain nerve fibers (neurilemma or sheath of Schwann) causes excessive growth (hypertrophy) of the peripheral nerve roots and nerve clusters (ganglia), with destruction of part of the nerve cell (axon). The age of onset, clinical findings and prognosis are similar to those of CMT disease. (For more information, chose "Dejerine" as your search term in the Rare Disease Database.) Hereditary sensory radicular neuropathy is a dominant hereditary disorder characterized initially by pain and loss of thermal sensation in the foot and lower leg. Later, attacks of sharp pain throughout the body may occur with weakness and ulcers on toes. Refsum Syndrome (Phytanic Acid Storage Disease) is a rare recessive genetic disorder of fat (lipid) metabolism characterized by peripheral neuropathy, impaired muscle coordination (ataxia), Retinitis Pigmentosa (RP), deafness, and bone and skin changes. It is associated with marked accumulation of phytanic acid in the blood plasma and tissues. The disorder may be due to the absence of phytanic acid hydroxylase, an enzyme needed for the metabolism of phytanic acid. Prolonged treatment with a diet lacking in phytanic acid can be therapeutic. (For more information, choose "Refsum" and "RP" as your search terms in the Rare Disease Database.) Familial Amyloid Neuropathy is a very rare genetic disorder inherited through autosomal dominant genes. It is characterized by abnormal accumulations of amyloid in the peripheral nerves. The location of the specific genetic mutation that causes this disorder is unknown. Therapies: Standard Scientists have developed a blood test that may be used in some situations to diagnose CMT. The test determines if deoxyribonucleic acid (DNA) is duplicated on chromosome 17. Treatment of CMT disease is symptomatic and supportive. Vocational counseling, anticipating progression of the disorder, may be useful for young patients. Use of braces can help correct foot drop. Orthopedic surgery to stabilize the foot may be of value. Therapies: Investigational Research is ongoing into possible new therapies for Charcot-Marie-Tooth Disease. For the most current information, please contact the agencies listed in the Resources section of thisa report. The Mayo Clinic, 200 First St., SW, Rochester, MN, 55905, has received permission from the FDA to test it's orphan drug, Dynamine, for treatment of Charcot-Marie-Tooth Disease. This disease entry is based upon medical information available through March 1993. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Carcot-Marie-Tooth Disease, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Charcot-Marie-Tooth Association Crozer Mills Enterprise Center 601 Upland Ave. Upland, PA 19015 (215) 499-7486 Charcot-Marie-Tooth International 1 Spring Bank Dr. St. Catherines, Ontario L2S 2K1 Canada (416) 687-3630 NIH/National Institute of Neurological Disorders & Stroke (NINDS) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5751 (800) 352-9424 For genetic information and genetic counseling referrals, please contact: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References CECIL TEXTBOOK OF MEDICINE, 18th ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Eds.: W. B. Saunders Co., 1988. Pp. 2264, 2155. MENDELIAN INHERITANCE IN MAN, 8th ed.: Victor A. McKusick; Johns Hopkins University Press, 1986. Pp. 140-3, 860, 1262.