Charcot-Marie-Tooth disease Health Article

Definition

Charcot-Marie-Tooth disease (CMT) is the name of a group of inherited disorders of the nerves in the peripheral nervous system (nerves throughout the body that communicate motor and sensory information to and from the spinal cord) causing weakness and loss of sensation in the limbs.

Description

CMT is named for the three neurologists who first described the condition in the late 1800s. It is also known as hereditary motor and sensory neuropathy and is sometimes called peroneal muscular atrophy, referring to the muscles in the leg that are often affected. The age of onset of CMT can vary anywhere from young childhood to the 50s or 60s. Symptoms typically begin by the age of 20. For reasons yet unknown, the severity in symptoms can also vary greatly, even among members of the same family.

Although CMT has been described for many years, it is only since the early 1990s that the genetic cause of many types of CMT have become known. Therefore, knowledge about CMT has increased dramatically within a short time.

The peripheral nerves

CMT affects the peripheral nerves, those groups of nerve cells carrying information to and from the spinal cord and decreases their ability to carry motor commands to muscles, especially those furthest from the spinal cord located in the feet and hands. As a result, the muscles connected to these nerves eventually weaken. CMT also affects the sensory nerves that carry information from the limbs to the brain. Therefore, people with CMT also have sensory loss. This causes symptoms such as not being able to tell if something is hot or cold or difficulties with balance.

There are two parts of the nerve that can be affected in CMT. A nerve can be likened to an electrical wire, in which the wire part is the axon of the nerve and the insulation surrounding it is the myelin sheath. The job of the myelin is to help messages travel very fast through the nerves. CMT is usually classified depending on which part of the nerve is affected. People who have problems with the myelin have CMT type 1 and people who have abnormalities of the axon have CMT type 2.

Specialized testing of the nerves, called nerve conduction testing (NCV), can be performed to determine if a person has CMT1 or CMT2. These tests measure the speed at which messages travel through the nerves. In CMT1, the messages move too slow, but in CMT2 the messages travel at the normal speed.

Genetic profile

CMT is caused by changes (mutations) in any one of a number of genes that carry the instructions to make the peripheral nerves. Genes contain the instructions for how the body grows and develops before and after a person is born. There are probably at least 15 different genes that can cause CMT. However, as of early 2001, many have not yet been identified.

CMT types 1 and 2 can be broken down into subtypes based upon the gene that is causing CMT. The subtypes are labeled by letters. So there is CMT1A, CMT1B, etc. Therefore, the gene with a mutation that causes CMT1A is different from that which causes CMT1B.

CMT1A

The most common type of CMT is called CMT1A. It is caused by a mutation in a gene called peripheral myelin protein 22 (PMP22) located on chromosome 17. The job of this gene is to make a protein (PMP22) that makes up part of the myelin. In most people who have CMT, the mutation that causes the condition is a duplication (doubling) of the PMP22 gene. Instead of having two copies of the PMP22 gene (one on each chromosome), there are three copies. It is not known how this extra copy of the PMP22 gene causes the observed symptoms. A small percentage of people with CMT1A do not have a duplication of the PMP22 gene, but rather have a point mutation in the gene. A point mutation is like a typo in the gene that causes it to work incorrectly.

Hereditary neuropathy with liability to pressure palsies (HNPP)

HNPP is a condition that is also caused by a mutation in the PMP22 gene. The mutation is a deletion, resulting in only one copy of the PMP22 gene instead of two. People who have HNPP may have some of the signs of CMT. However, they also have episodes where they develop weakness and problems with sensation after compression of certain pressure points such as the elbows or knee. Often, these symptoms will resolve after a few days or weeks, but sometimes they are permanent.