Charcot-Marie-Tooth disease is a group of disorders that affect the peripheral nerves — the nerves that carry messages between the brain and muscles throughout the body. It is named after the three doctors who described it in 1886: Jean Martin Charcot and Pierre Marie in Paris, and Howard Henry Tooth in Cambridge, England. Charcot-Marie-Tooth disease is also sometimes referred to as hereditary motor and sensory neuropathy (HMSN) or peroneal muscular atrophy.
All types of Charcot-Marie-Tooth disease (CMT) cause degeneration of the peripheral nerves, leading to muscle weakness and some loss of sensation in the arms, legs, hands, and feet. These symptoms often first appear during adolescence or early adulthood, but can develop later in life, as well.
Symptoms vary greatly among people with CMT, and usually begin in the feet and legs. As CMT progresses, it can cause deformities in the bones of the feet, such as hammertoes and high arches. Without treatment, walking may become difficult.
Although there is no cure for Charcot-Marie-Tooth disease, there are many treatment options and assistive devices to help people manage physical challenges and lead fulfilling lives.
This illustration shows nerves in the lower leg and foot that may be affected by CMT, leading to muscle loss and weakness.
Reproduced with permission from J Bernstein, ed: Musculoskeletal Medicine. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2003.
Charcot-Marie-Tooth disease is an inherited disorder, which means it runs in families. Therefore, people with a family history of CMT are at a higher risk of developing the disease.
Most types of CMT are caused by defects in genes that affect two specific parts of nerves: axons and myelin.
Nerves travel from the spinal cord to the arms and legs, reaching distant parts of the body through long, thin extensions called axons. Information from the brain is carried along axons via electrical impulses. Myelin is a tissue that covers and insulates axons. Axons wrapped in myelin conduct signals more quickly than nerve cells that are not wrapped in myelin.
In Charcot-Marie-Tooth disease, gene mutations disrupt the function of either myelin or axons. This slows the signals to and from the brain. Muscles that do not receive normal nerve signals become progressively weaker.
Although most people with CMT have inherited the disorder, there are some cases of gene mutation that occur spontaneously. These spontaneous instances of CMT can also be passed along to future generations.
People with CMT have varied symptoms, depending upon the type of CMT they have, as well as the severity of their disease. In general, symptoms fall into three major categories:
- Muscle weakness
- Bone deformity
- Loss of sensation
Most people first notice CMT symptoms in their feet and legs. This is a slowly progressive disorder. Over time, symptoms may also affect the hands and arms.
Weakness in the muscles of the foot, ankles, and lower leg can result in a foot drop, which is the inability to dorsiflex the foot and hold it horizontal when walking. This results in an abnormal "steppage" gait. People with a steppage gait tend to lift the affected leg higher as it swings through in order to allow the foot to clear the floor. Trips and falls become more frequent.
In addition, the muscles in the lower leg may become smaller (atrophy) which can cause the lower leg to appear quite thin. This is sometimes described as a "stork leg" appearance.
Hand weakness may first become apparent as deterioration in handwriting or clumsiness and dropping things. The muscles in the hands may also atrophy.
Weakened muscles lead to muscle imbalance, and bones may not be supported in a normal position. In the foot, muscle imbalance can lead to bone deformities like hammertoes and high arches.
Less commonly, more severe cases of CMT can affect the muscles closer to the center of the body. The muscles supporting the hip can be affected, resulting in hip dysplasia. Muscle imbalance in the abdomen and back could result in curvature of the spine (scoliosis).
Loss of Sensation
People with CMT often lose some sensation in their feet and hands. The lack of sensory feedback to the brain may affect a person's ability to feel normal pain. As a result, minor injuries, such as a blister on the toe, may become infected without notice.
Although Charcot-Marie-Tooth disease typically does not cause pain, it may lead to numbness or tingling.
In this young person with CMT, the calf and ankle muscles have weakened and show atrophy, particularly on the right leg. In addition, the feet have abnormally high arches.
If your doctor suspects Charcot-Marie-Tooth disease, he or she may refer you to a neurologist for a more comprehensive evaluation.
Patient History and Physical Examination
During the first appointment, your doctor will ask you to describe your symptoms, and also discuss your general health and past illnesses. Tell your doctor if anyone in your family has ever had similar symptoms.
During the physical examination, your doctor may check for the most common signs of Charcot-Marie-Tooth disease, including muscle weakness (decreased muscle bulk and difficulty with certain tasks), decreased deep tendon reflexes, bone deformity, and sensory loss.
Your doctor may order tests to help determine the exact cause of your symptoms.
This weightbearing x-ray shows an abnormally high arch of the foot.
- X-rays. These tests provide clear images of bone. Weightbearing foot x-rays can document the severity of deformity. X-rays may also be obtained to check for scoliosis or hip dysplasia, conditions that occur less frequently than foot problems in people with CMT.
- Nerve conduction and electromyograpy studies. These tests can determine how well the nerve is working. During a nerve conduction test, the nerve is stimulated in one place and the time it takes for there to be a response is measured. In electromyography, the responses of muscles to electrical stimulation are tested.
- Nerve biopsy. A small incision is made in the calf of the leg and a small piece of peripheral nerve is removed. In nerves damaged by CMT, the myelin that surrounds the nerve tissue has an "onion bulb" appearance when examined under a microscope.
- Genetic testing. Laboratory blood tests can check for the most common gene mutations that cause CMT. Although it is the most definitive test for the disease, genetic testing cannot identify all cases of CMT.
There is no cure for Charcot-Marie-Tooth disease. However, there are many treatment options to help you manage the effects of the disorder.
Several medical specialists are typically involved in the ongoing care of people with CMT. These include orthopaedic surgeons, physical therapists, occupational therapists, orthotists, and podiatrists.
Physical therapy. Specific exercises to improve muscle strength and flexibility will help you maintain mobility and independence. A physical therapist can develop a program that includes strengthening exercises, stretching, and muscle endurance activities — such as low-impact aerobics and swimming.
Assistive devices. Braces, such as ankle-foot orthoses (AFOs), can support the feet in proper position and address gait problems, such as foot drop. Custom-made shoes and shoe inserts can help to fit high arches or hammertoes.
A foot-ankle orthosis (AFO) provides support for the ankle and stabilizes the foot while walking.
Reproduced with permission from Sussman MD: The orthopaedic management of cerebral palsy. Orthopaedic Knowledge Online Journal 2009. Accessed December 2013.
Occupational therapy. Over time, people with CMT may develop hand and arm weakness. Typical daily activities, such as fastening buttons or writing, can become difficult. An occupational therapist can provide a program to help maintain fine finger movements, as well as offer assistive tools to accomplish daily activities.
Foot care. Sensory loss in the feet can allow small blisters or sores to progress to a serious infection in a short time. Inspect your feet daily for any problems. Choose well-fitting shoes. See a podiatrist for removing calluses that may develop due to foot deformities.
Medication. Although CMT causes loss of sensation, some patients have pain due to nerve damage or muscle cramping. Your doctor can prescribe medication to help relieve these types of pain.
Your doctor may recommend surgery to correct foot deformities. Procedures to straighten toes or lower arches can help improve foot positioning and relieve pain. Surgery can also help address shoe-wear problems.
Although surgery can address bone deformity, it cannot improve muscle weakness or sensory loss.
Charcot-Marie-Tooth disease progresses slowly over time. Symptoms may worsen, even with proper treatment and the patient's best efforts. Although many people have emotional assistance from family and friends, support groups are available to help people with CMT and their families cope with the progressive nature of the disorder.
In addition to organized support groups, people with CMT can also turn to medical professionals for support. Doctors, physical and occupational therapists, and assistive technology professionals are an excellent resource for help in managing and living with the disorder.
Genetic counseling is also recommended to help patients understand the inheritance pattern of their condition and assist with family planning.