Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease is a group of neuromuscular disorders that primarily affect the peripheral nerves. These nerves connect the spinal cord and brain with muscles and sensory organs.

Nerve cells, or neurons, communicate information through electrical signals that travel along a long, thin part of the cell called the axon. Myelin, a substance that wraps around the axon, prevents the dissipation of electrical signals and speeds up communication. If the axons or myelin sheaths are damaged, peripheral nerve cells cannot activate muscles or transmit sensory information correctly.

The main symptoms of Charcot-Marie-Tooth disease are muscle weakness and wasting, as well as loss of sensation in the extremities, including the feet, lower legs, hands, and forearms.

The disease usually starts in adolescence or early adulthood, but it can begin at any time from childhood to late adulthood. The first symptoms are often muscle weakness in the feet, leading to abnormalities such as pes cavus, in which the arch of the foot is raised more than normal, or hammertoes, an abnormal bend of the toes. As the disease progresses, the muscles in the lower legs and ankles weaken, and muscle weakness in the hands often occurs too. People with this disorder may also experience pain or burning in the feet and lower legs, or even decreased sensation to touch, heat, and cold. In rare cases, this loss of sensation can lead to a loss of hearing or vision. The symptoms can vary in severity even in individuals from the same family, although this disorder does not usually affect life expectancy in most patients.

Although there is no cure for Charcot-Marie-Tooth disease, physical and occupational therapy, splinting, and other orthopedic devices, even orthopedic surgery, can go a long way in relieving the characteristic symptoms. Physical and occupational therapy involves exercises to strengthen muscles, stretching, and moderate aerobic exercise, such as cycling or swimming. Some patients require ankle or thumb splints or other orthopedic devices to maintain mobility and prevent possible injury.

• Charcot-Marie-Tooth type 1: It is the most common type and is related to abnormalities in the myelin layer, the substance that protects the axons of nerve cells.
• Charcot-Marie-Tooth type 2: It is less common than type 1 and is characterized by abnormalities in axons themselves.
• Charcot-Marie-Tooth type 3: Also known as Dejerine-Sottas disease. This disease is uncommon but a severe neuropathy that also affects myelin, with onset during infancy. Babies suffer from severe muscle atrophy and weakness, as well as sensory issues.
• Charcot-Marie-Tooth type 4: This type can affect both the axon and the myelin layer and is usually identified based on its inheritance pattern. Patients suffering from this type of disorder usually present with leg weakness in their childhood and may even lose their ability to walk during adolescence.
• Charcot-Marie-Tooth type X: It is a disorder related to a point mutation in a gene located in the X chromosome. Symptoms can range from mild to moderate and usually start in late childhood or adolescence.

There are several subtypes within the aforementioned types, which are distinguished by the specific gene that is altered.

It is one of the most common inherited neurological disorders, affecting approximately one in 2,500 people worldwide and occurring equally in all races and ethnic groups.

The inheritance patterns of this disease change depending on the type. In type 1 and in most type 2 cases, as well as in most intermediate forms of the disease, the inheritance pattern is autosomal dominant, i.e., a single copy of the altered gene is sufficient for the disease to occur. In most of these cases, the affected individuals have an affected parent.

Type 3, or Dejerine-Sottas disease, is usually autosomal recessive, i.e. two copies of the altered gene are necessary for the disease to occur. Charcot-Marie-Thooth disease type 4 and some cases of type 2 are also inherited following an autosomal recessive inheritance pattern.

Type X follows an X-linked dominant inheritance pattern, i.e. the altered gene is located in the X chromosome, which makes inheritance different for boys and for girls.

In rare occasions, the genetic mutation that causes Charcot-Marie-Tooth disease is a new mutation that occurs spontaneously and is not present in the parents.

In individuals affected by Charcot-Marie-Tooth disease, physical and occupational therapy, as well as the use of splints or other orthopedic devices, may help maintain mobility and prevent potential injuries.

On the other hand, a genetic counseling consultation is recommended to future parents who suffer from the disease or are aware of cases in the family; in this way, they can know the risk of transmitting the disease to their offspring, perform the genetic tests that are deemed necessary, and take the appropriate prevention measures.

BENE – Association of neuromuscular disease patients and families of Bizkaia

ASEM – Spanish Neuromuscular Disease Federation

CMTA– Charcot-Marie-Tooth Association

Data sheet for Charcot-Marie-Tooth disease by ASEM.