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CHARCOT-MARIE-TOOTH DISEASE (CMT)

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CHARCOT-MARIE-TOOTH DISEASE (CMT)

Charcot-Marie-Tooth disease is a group of inherited disorders that affect the peripheral nerves.

  • The peripheral nerves are the nerves outside the main central nervous system – the spinal cord and brain.
  • These nerves control muscles and send data from the arms and legs to the brain, allowing a person to sense touch.
  • A peripheral nerve contains two main part, the axon, which is the inside of the nerve, and the myelin sheath, which is a protective layer around the axon.
  • The condition can either affect the axon or myelin sheath, or both.
  • The name of the condition comes from the three physicians who first described it: Jean Charlot, Pierre Marie, and Howard Henry Tooth.
  • Also referred to as hereditary motor and sensory neuropathy, Charcot-Marie-Tooth Disease is the most commonly inherited neurological disorder affecting about 1 in 2,500 people.

CAUSES

CMT is an inherited genetic condition that is caused by mutations in one or more genes. These mutations disturb the function and structure of the peripheral nerve axon and myelin sheath and may cause them to degenerate, impairing the conductance of nerve signal between the brain and the extremities.

The gene can be inherited from one or both parents, or in rare cases, a person might be born spontaneously with the condition without inhering it from their parents.

There are 5 main types of CMT each with different causes.

CMT1 is the most common type and accounts for about one-third of all cases. It is caused by genetic defects that damage the myelin sheath protecting the nerves and is commonly referred to as demyelinating CMT. It is further divided into subtypes A-F according to the genes mutated.

  • CMT1A is the most common subtype of CMT1 and is caused by a duplication of the PMP22 gene on chromosome 17.
  • CMT1B is the second most common subtype caused by a mutation in the MPZ gene on chromosome 1.
  • Other subtypes are rare and include CMT1C caused by a defect in the LITAF gene, CMT1D caused by a defect in ERG2 gene, CMT1E caused by a defect in the PMP22 gene, and CMT1F caused by a defect in the NEFL gene.

CMT2 is caused by defects in the gene that play important roles in the structure and function of the axon, and it is commonly called axonal CMT. It is also divided into subtypes.

  • CMT2A is the most common subtype of CMT2 and is caused by defects in the MFN2 gene that codes mitofusin 2.
  • Other rare subtypes are CMT2B caused by defects in the RAB7 gene, CMT2C caused by defects in the TRPV4 gene, CMT2D caused by defects in the GARS gene, and others.

CMT3, also called Dejerine-Sottsass disease is a rare form that is caused by defects in the P0 or PMP22 gene.

CMT4 is also a rare type affecting the myelin sheath and usually inherited in the autosomal recessive pattern. It begins in early childhood and has its subtypes.

  • CMT4A caused by mutations in the GDPA1, CMT4B1 caused by a defect in MTMR2 gene, CMT4B2 caused by mutations in the MTMR13, and other gene defects such as SH3TC2, NDG1, EGR2, PRX, and FIG4.

CMT-X is caused by mutations in the GJB1 gene located on the X-chromosome. This gene encodes for a protein called connexin-32.

SYMPTOMS

  • Weakness in the legs, feet, and ankle
  • High foot arches
  • Decreased ability to run
  • Difficulty standing and walking
  • Loss of muscle bulk in the legs and feet
  • Hammer toes (curled toes)
  • Frequent falling or tripping
  • Muscle fatigue
  • Loss of touch sensation in the arm, legs, feet
  • Higher than normal or awkward gait.

DIAGNOSIS AND TREATMENT

To make a diagnosis, the doctor will carry out a physical examination. During the physical examination, the doctor will check for signs of muscle weakness in your hands, arm and feet, foot deformities including hammer toes or high foot arches, and reduced reflexes.

Other tests include:

  • Nerve conduction studies to measure the speed and strength of electrical signals transmitted through your nerves.
  • Electromyography to measure electric activity as a person relaxes or tighten the muscles.
  • Nerve biopsy where a piece of peripheral nerve is taken from the calf for testing in the lab
  • Genetic testing is usually done using blood samples to check where a person carries the faulty gene or genes.
TREATMENT

No cure exists for the condition. The goal of the treatment option is to manage the symptoms.

Treatment option may include:

Medications to treat the pain that is associated with muscle cramps or nerve damage.

Therapy such as

  • Physical therapy that uses low-impact exercises and stretching techniques to help strengthen and stretch the muscle to prevent muscle tightening and loss.
  • Occupational therapy that can help with assistive devices such as rubber grips on door knobs.
  • Orthopedic devices that involve using leg and ankle braces to provide stability while walking.

Surgery for severe foot deformities.