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$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}
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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
     [phone]

     Charcot-Marie-Tooth Association
     Crozer Mills Enterprise Center
     601 Upland Ave.
     Upland, PA 19015
     [phone]

     Charcot-Marie-Tooth International
     1 Spring Bank Dr.
     St. Catherines, Ontario L2S 2K1
     Canada
     [phone]

     NIH/National Institute of Neurological Disorders & Stroke (NINDS)
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]
     [phone]

For genetic information and genetic counseling referrals, please contact:

     March of Dimes Birth Defects Foundation
     1275 Mamaroneck Avenue
     White Plains, NY  10605
     [phone]

     Alliance of Genetic Support Groups
     35 Wisconsin Circle, Suite 440
     Chevy Chase, MD  20815
     (800) 336-GENE
     [phone]

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.