Charcot-Marie-Tooth Disease (CMT)
Causes of CMT
CMT damages the peripheral nerves that connect the spinal cord to the rest of the body. The peripheral nerve fibers, called axons, extend from sensory nerve cells in the body's periphery back toward the spinal cord, and from muscle-controlling nerve cells in the spinal cord out toward the muscles. Axons transmit electrical signals for sensation and movement to and from the spinal cord.
More than 30 genes have been implicated in CMT. In different types of CMT, peripheral nerve damage can be caused by defects in genes coding for proteins affecting axons, or by defects in genes coding for proteins affecting the insulating myelin coating around each axon — or both.
In order for a person to move and react with precision and speed, axons have to transmit their signals within a fraction of a second. This is a real challenge for axons that have to stretch over long distances, like the ones connected to muscles in fingers and toes.
The longest axons in the body are especially sensitive to damage, which explains why CMT mostly causes motor and sensory problems in the body’s extremities.
Inheritance patterns in CMT
Although CMT can look very similar to an acquired neuropathy — a type of nerve damage caused by diabetes, immunological abnormalities, or exposure to certain chemicals or drugs — it is not caused by anything a person does, and it is not contagious. It is hereditary, meaning that it can be passed down through a family from one generation to the next.
Because of these features, CMT is sometimes called hereditary motor and sensory neuropathy (HMSN). Some doctors also use the older name, peroneal muscular atrophy, which refers to atrophy of the peroneal muscle in the lower part of the leg.
CMT can run in a family, even when there is no obvious family history. In part, this is because CMT can be inherited in three different ways — X-linked, autosomal dominant, and autosomal recessive — that are not always easy to trace through a family tree.
X-linked inheritance means that the genetic defect (or mutation) is located on the X chromosome. In females, who have two X chromosomes, a normal copy of the gene on one chromosome can often compensate (at least partially) for the defective copy. Therefore, X-linked diseases usually affect males more severely than females, because males have only one X chromosome. X-linked diseases (like CMTX) cannot be passed from father to son.
Autosomal inheritance means the mutation occurs on a chromosome other than the X or Y. Therefore, autosomal diseases affect males and females equally. Autosomal recessive inheritance means that two copies of a defective gene are required for the disease to appear. One copy is inherited from each parent, neither of whom would normally have the disease.
Autosomal dominant inheritance means one copy of a defective gene is enough to cause disease. A person who inherits the defective gene from a parent will have the disease, as will the parent.
When CMT is passed on in an autosomal dominant pattern, it can be easy to recognize in the family tree. In contrast, X-linked or autosomal recessive types of CMT might seem to occur “out of the blue.” In reality, the mother or both parents might be carriers who silently harbor a genetic mutation. Many parents have no idea they are carriers of a disease until they have a child with the disease.
CMT also can occur when a new mutation occurs during the child’s conception. These are called spontaneous mutations, and after they occur, they can be passed on to the next generation.
Your risk of inheriting or passing on CMT depends largely on what type of CMT you have.
A good way to find out more about this risk is to talk with your MDA Care Center physician, or a genetic counselor on your MDA care team. Also, see Facts About Genetics and Neuromuscular Diseases.