Introduction
Questions and Answers
Inheritance Patterns
MDA's Search for a Cause
MDA's Search for a Treatment or Cure
 |
QUESTIONS AND ANSWERS
 What is CMT?
CMT is actually a broad term used to describe a group of genetic disorders that affects the peripheral nerves, which carry motor (relating to movement) and sensory (relating to sensation) signals between the brain and spinal cord and the rest of the body.
CMT most frequently affects the lower legs, feet and hands, resulting in weakness and atrophy, or loss of muscle bulk (see illustration, right), as well as causing a mild degree of loss of sensation. However, the motor problems are much more significant than the sensory problems, which are usually minor.
About one in 2,500 people has a form of CMT. Overall, it affects about 100,000 to 125,000 people in the United States alone, making it one of the most common hereditary disorders.
Are there other names for CMT?
Yes. CMT disorders are sometimes referred to as hereditary motor and sensory neuropathies (HMSNs). An old name for CMT is peroneal muscular atrophy. The peroneal muscles are in the lower leg and may atrophy in this disorder.
Is there more than one variety of the disease?
 CMT is usually divided into types 1 and 2, according to the specific site of the peripheral nerve problem. About two-thirds of people with CMT have type 1, which affects the myelin sheath, the insulating covering that surrounds nerve fibers (see illustration, right). Approximately one-third of patients have type 2, which affects the nerve fibers (also called axons) themselves. The peripheral nerves are made of bundles of these fibers.
Some physicians use the term type 3 CMT to describe a disease that is also known as Dejerine-Sottas disease (see below). This is a severe form of CMT.
Nerve fibers are often compared to electrical wires and myelin to insulation, and the comparison holds up fairly well. However, whereas electrical impulses can travel along an uninsulated wire, nerve impulses travel very poorly along an uninsulated fiber.
Doctors can check the function of the myelin sheath by measuring the speed with which nerve impulses travel from one point to another along a nerve. In type 1 CMT, the nerve impulses travel more slowly than is normal. In type 2 CMT, the speed of nerve impulses is normal, but the size or amount of the impulses is smaller than normal, indicating a problem with the axons (nerve fibers).
CMT can be further classified by the location of the genetic defect that underlies the disorder. For example, type 1 CMT, caused by a defect on chromosome 17, is called CMT1A, and type 1 CMT, caused by a defect on chromosome 1, is CMT1B.
When do signs of the disease first become apparent?
Due to the slow progression of this disease, its onset is often difficult to determine.
Type 1 (the myelin-related type) is usually noticed during late childhood or adolescence. Type 2 (the axonal type) is often diagnosed a little later than type 1.
What are the early symptoms of CMT?
 The first symptoms of CMT are usually foot abnormalities, such as a high arch or flexed toes (see illustration, right). It can be difficult to hold up the foot, which may result in tripping on curbs, having to take a higher than normal step (picking up the foot by bending the knee), and walking with deliberation.
How disabling is CMT?
CMT varies highly in severity, even among members of the same family. Some people are so mildly affected they don't notice any symptoms. For those with symptoms, foot abnormalities and walking difficulties pose the most serious problems.
Although exceptions exist, most people with CMT have trouble participating in sports. Sprained ankles and fractures of the ankles and lower legs are common. The leg and foot problems are rarely disabling enough to require a wheelchair, and many people with CMT pursue active, vigorous lives.
If the muscles of the hands are affected, aids may be required for such daily activities as writing, fastening buttons and turning door knobs and screw caps.
CMT doesn't affect most physical functions, including the cardiovascular system, and has no effect on intellect. Life expectancy isn't shortened by CMT.
How is CMT diagnosed?
A diagnosis is reached after an experienced doctor performs a thorough physical examination, notes a CMT-like pattern of foot, leg and hand weakness, and obtains a family history. The doctor will often then order tests to confirm the suspected diagnosis of CMT.
An important test is one known as nerve conduction velocity, or NCV, which measures the speed at which nerve impulses travel along the nerves. Nerve impulses are slowed in type 1 CMT and may show other abnormalities in type 2 CMT.
Another useful test is an electromyogram, or EMG, which records the electrical activity of muscle cells. Damage to nerves causes the muscles that would normally receive signals from those nerves to show a characteristic pattern of electrical activity.
These tests may be somewhat uncomfortable, but they're extremely valuable, because they allow nerve function to be directly examined. They serve a function similar to that served by electrocardiograms in diagnosing heart problems.
Other testing is sometimes done to exclude the possibility of disorders with signs and symptoms similar to those of CMT.
Genetic testing is available for at least one form of CMT (the type caused by a defect on chromosome 17), but new developments in CMT genetic testing are expected. See your MDA clinic physician or genetic counselor for up-to-date information about genetic testing.
What causes CMT?
CMT is caused by defects in genes that affect the function of the peripheral nerves. Genes are the instructions, or "blueprints," for proteins in the body. When a gene is abnormal, the protein is likewise abnormal, or altered. The genes that, when altered, cause CMT, affect either the nerve fiber itself or the myelin sheath that surrounds it.
MDA-supported researchers have so far identified three genes that, when abnormal, result in type 1 CMT. The genes are on chromosomes 1, 17 and the X chromosome. All of them affect myelin, and the X chromosome type may affect the nerve fiber itself as well.
The most common form of CMT is the kind that involves a gene on chromosome 17 known as PMP22, or peripheral myelin protein 22. The problem is usually a duplication of a small section of chromosome 17 that includes the PMP22 gene. Patients with this type of CMT actually have a total of three copies of the PMP22 gene in each cell, instead of the usual two copies. Having this extra copy leads to the CMT symptoms. In a few cases, a different kind of problem -- one that alters the PMP22 gene itself instead of duplicating it -- has been found.
Other patients with type 1 CMT have a defect in a gene on chromosome 1 known as the myelin protein zero (P0) gene.
Both the chromosome 17 type and the chromosome 1 type are inherited in an autosomal dominant pattern, which means that a child only needs to inherit an abnormal gene from one parent to show symptoms of the disease (see "Inheritance Patterns").
Still other patients with type 1 CMT have a defect in a gene located on the X chromosome known as connexin 32 (Cx32).
Females have two X chromosomes and males have an X and a Y chromosome. Because of this difference, females are usually not as severely affected by genetic abnormalities on the X chromosome as are males and often escape symptoms of an X chromosome disease entirely. This is because they have a normal gene on the other X chromosome to serve as a "backup." Males, with their single X chromosome, have no such backup and usually show more severe symptoms.
In Cx32-related CMT, girls and women show the disease to varying degrees. This has prompted researchers to call Cx32-related CMT an X-linked dominant condition. In X-linked dominant conditions, males and females need only one abnormal X chromosome gene to show the disease (see "Inheritance Patterns").
Type 2 (axonal) CMT is usually inherited in an autosomal dominant pattern. The genes for type 2 CMT haven't been specifically identified, but two of them have been mapped to small regions of chromosomes 1 and 3.
In at least some patients with X-linked CMT, there are features that resemble type 2 CMT.
(Note: Although autosomal and X-linked dominant diseases can be inherited when an affected parent passes the gene to his or her child, they aren't necessarily inherited -- at least not in this strict sense. Genes are carried from parent to child via sperm and egg cells, and sometimes genetic defects occur only in these cells, not in the rest of the parent's cells. In these cases, parents won't show any disease symptoms and genetic testing of parents won't reveal any defects.)
Is Charcot-Marie-Tooth disease contagious?
No. Genetic diseases are not contagious.
Is there any cure or treatment for the disease?
There is no cure for CMT, although MDA-supported research is aimed at understanding exactly how the gene defects lead to the disease, with the ultimate goal of compensating for these defects.
For now, treatment may involve physical therapy, lightweight lower leg braces (see illustration, right) or shoe inserts, and sometimes surgery to correct foot deformities.
Dejerine-Sottas Disease
Dejerine-Sottas disease is closely related to CMT and is, in fact, sometimes referred to as type 3 CMT. However, many clinicians still refer to it by the names of the French doctors who first described it in the late 19th century, Joseph Jules Dejerine and Jules Sottas.
Characteristics of Dejerine-Sottas disease include:
- slow development of early motor skills, including walking, which is sometimes not achieved until the third or fourth year;
- possible loss of the ability to walk during the adult years;
- hearing loss in some cases;
- severe sensory problems;
- an autosomal dominant inheritance pattern when inheritance can be traced.
Dejerine-Sottas disease can be caused by abnormalities in the same genes that can cause two forms of type 1 CMT -- the PMP22 gene on chromosome 17 and the P gene on chromosome 1. However, the defects in these genes are not the same defects that cause the type 1 CMT disorders. Researchers are studying mice and rats with defects that cause a Dejerine-Sottas-like condition.
As with CMT, there are likely to be other genes that, when abnormal, can cause this disorder.
Dejerine-Sottas disease often occurs without a family history.
Back to Disease Brochures |
