Charcot-Marie-Tooth disease (CMT)

Charcot-Marie-Tooth disease (CMT) is an umbrella term for a range of inherited genetic conditions that affect the peripheral nervous system. The peripheral nervous system controls your ability to move and feel parts of your body, such as your hands and feet. Conditions of the peripheral nerves – the nerves stretching from the spinal cord to the muscles – are known as neuropathies. Around one in 2,500 people are thought to be affected, making CMT the most common inherited condition of the peripheral nervous system.

CMT takes its name from the three doctors who first recognized it: Jean-Marie Charcot and Pierre Marie from France, and Howard Henry Tooth from the United Kingdom. Other names for CMT include peroneal muscular atrophy, hereditary motor and sensory neuropathy types I, II and X, and progressive neuropathic muscular atrophy.

The peripheral nervous system#

Nerve tissue outside the brain and spinal cord makes up the peripheral nervous system. (The brain and spinal cord together form the central nervous system.) This system produces body movements by contracting and relaxing the muscles under instruction from the brain, and it relays sensory information from the skin, tendons and muscles back to the spinal cord.

The building block of the nervous system is the nerve cell, or neuron. Neurons send electrical impulses down nerve fibers called axons, which work like the wires in an electrical cable. Each axon is wrapped in an insulating sheath called myelin, which keeps the axon healthy and helps electrical impulses travel quickly.

CMT either interferes with the production of the proteins that make up the myelin sheath, or affects the structure or function of the axon. Neuropathies that affect myelin are called demyelinating neuropathies; those that mainly affect the nerve fibers are called axonal neuropathies. In both cases, affected nerves cannot work properly to control movement or sensation.

Symptoms#

In people with CMT, the nerves of the arms and legs work less well than usual. This happens gradually and leads to wasting of the muscles served by those nerves. The feet, legs and hands are often most affected, becoming weaker and harder to control over time.

Symptoms usually begin in childhood or the teenage years, and the legs are most commonly affected first. Symptoms are progressive and can include:

• ankle weakness, with the ankle “rolling over” – a common early symptom
• weakness in the muscles of the hands and feet, so that handgrip is affected and tasks like opening screw-top jars or turning taps become difficult
• high foot arches (known as pes cavus) and clawed toes
• a high-stepping gait and “slapping” of the feet on the floor while walking
• muscle wasting in the legs and arms
• poor balance and occasional falls
• loss of sensation, such as a reduced ability to feel pain in the feet and hands

The effects of CMT vary widely. Some people are only slightly affected and may manage with high-sided shoes; others may need walking aids such as sticks, and some may need to use a wheelchair.

How CMT is inherited#

Most inherited conditions are passed on through only one or two patterns of inheritance. CMT, however, can be inherited through most known patterns, including:

• Autosomal dominant – the child only needs to inherit one copy of the altered gene to have the condition. If either parent has CMT, there is a 50 per cent chance their child will also develop it.
• Autosomal recessive – the person must inherit two copies of the altered gene, one from each parent, to have the condition. Someone who carries only one copy is known as a carrier: they carry the gene but have no symptoms.
• X-linked – the altered gene is carried on the X chromosome, which is involved in determining a baby’s sex. Each child of a mother carrying the gene has a 50 per cent chance of inheriting the condition. Males are more affected than females, and females may be carriers without obvious effects. All daughters of an affected man inherit the gene, but none of his sons (there is no male-to-male transmission).

Different types of CMT are linked to changes in different genes. Examples include CMT Type 1A (a duplicated gene on chromosome 17), Type 1B (chromosome 1), Type 1C (chromosome 16), Type 2A (chromosome 1), Type 2B (chromosome 3), Type 2C (chromosome 12), Type 2D (chromosome 7) and X-linked CMT (a change on the X chromosome). A number of newer genes have also been discovered that cause some less common forms.

Diagnosis#

CMT is diagnosed using a number of tests, including:

• Physical examination – strength testing and assessment of reflexes and sensation. Common findings are loss of the muscle stretch reflexes (especially the ankle jerk reflex) and weakness when lifting the feet (ankle dorsiflexion) and bringing the thumb upward (thumb abduction).
• Nerve conduction tests – used to measure the strength and speed of nerve signals to determine which form of CMT is present. For example, nerve responses are much smaller than usual in axonal CMT, and nerve signals travel much more slowly in demyelinating forms.
• Genetic tests – used to identify the altered gene. For example, CMT Type 1A can be diagnosed with a relatively routine test called a chromosome microarray.
• Biopsy – small samples of nerve or muscle tissue are removed and examined in a laboratory. This is not commonly done and is usually unnecessary if a genetic change is found.

Genetic counseling#

If you or a family member have been diagnosed with CMT, or if it runs in your family, it may help to speak to a genetic counselor. Genetic counselors are health professionals qualified in both counseling and genetics. They provide emotional support and information for people and families affected by genetic conditions.

A genetic counselor can help you understand CMT and its causes, how it is inherited, and what a diagnosis means for your child’s health, lifestyle and future plans, as well as for your family. They can also provide information about genetic testing, and are trained to offer support that is sensitive to your family’s circumstances, culture and beliefs.

Treatment#

There is currently no cure for CMT, but treatment can help manage some of the symptoms. Options can include:

• leg and ankle braces or orthotics
• specially designed orthopedic shoes
• thumb splints
• physical therapy, muscle strength training and regular stretching
• regular, moderate, low-impact exercise such as swimming or cycling
• occupational therapy
• orthopedic surgery to correct deformities

Support organizations can provide information and connect you with other individuals and families affected by CMT.

Key points#

• CMT is the most common inherited condition affecting the peripheral nervous system.
• The peripheral nervous system produces body movements by contracting and relaxing muscles under instruction from the brain.
• Symptoms usually begin in childhood or the teenage years, and the legs are most commonly affected first.
• Symptoms are progressive and can include ankle weakness, with “rolling over” of the ankle being a common early sign.

Where to get help#