Charcot-Marie-Tooth Disease (CMT)
Description
Charcot-Marie-Tooth disease (CMT) is a group of inherited disorders affecting the peripheral nerves, the nerves that connect the spinal cord and brain to the rest of the body. This leads to muscle weakness, particularly in the feet and legs, and can also cause sensory problems and loss of reflexes. Learn more about the signs, symptoms, causes, diagnosis, and management of this condition, including strategies for living a fulfilling life.
Genes Involved
CMT is caused by mutations in a variety of genes, depending on the specific type of CMT. The most commonly involved genes include:
- MPZ (myelin protein zero): Mutations in this gene are responsible for the most common form of CMT, CMT1A.
- GJB1 (gap junction protein beta 1): Mutations in this gene cause CMT1X, a type of CMT that is linked to the X chromosome.
- MFN2 (mitofusin 2): Mutations in this gene cause CMT1A, CMT1X, and CMT4A.
- SH3TC2 (SH3 domain containing transmembrane protein 2): Mutations in this gene cause CMT4C.
- GDAP1 (ganglioside-induced differentiation-associated protein 1): Mutations in this gene cause CMT4D.
The specific gene involved can help determine the type of CMT, the severity of the disease, and the potential for treatment.
Recognizing the Signs and Symptoms
The symptoms of CMT can vary depending on the type of CMT and the severity of the disease. Common symptoms include:
- Muscle weakness: This is usually the first symptom to appear, and it often starts in the feet and ankles, spreading to the legs and sometimes the hands and arms. This weakness can make it difficult to walk, run, or climb stairs.
- Foot deformities: The muscles in the feet can weaken, leading to high arches, hammertoes, and a tendency to walk on the balls of the feet.
- Loss of sensation: Some people with CMT may experience a loss of sensation in their feet and legs, which can make them more susceptible to injuries.
- Muscle atrophy: This is a wasting away of muscle tissue. The muscles in the feet and legs may become smaller and weaker over time.
- Loss of reflexes: The reflexes in the feet and legs can be absent or diminished.
- Slow nerve conduction: This can be detected by a nerve conduction study, which measures the speed at which electrical impulses travel through the nerves.
Symptoms typically appear in childhood or adolescence and worsen gradually over time. The rate of progression varies among individuals.
Causes
Charcot-Marie-Tooth disease is caused by mutations in genes that are responsible for producing proteins involved in the formation and maintenance of the myelin sheath. The myelin sheath is a fatty substance that wraps around nerve fibers, providing insulation and allowing electrical impulses to travel quickly and efficiently. When the myelin sheath is damaged, nerve signals can become slowed or blocked, leading to the symptoms of CMT.
There are two main types of CMT:
- CMT1 (demyelinating CMT): This type is caused by defects in the myelin sheath, which leads to a slowing of nerve conduction.
- CMT2 (axonal CMT): This type is caused by damage to the nerve axons themselves, which are the long, thin fibers that carry nerve impulses.
Inheritance/recurrence risk
CMT is usually inherited in an autosomal dominant pattern, which means that a person has a 50% chance of inheriting the disease from a parent who has CMT. Some types of CMT are inherited in an autosomal recessive pattern, which means that a person must inherit two copies of the mutated gene, one from each parent, to develop the disease. In these cases, both parents carry one copy of the mutated gene but do not have CMT themselves.
If one parent has CMT, there is a 50% chance of passing on the mutated gene to their children. If both parents have CMT, there is a 75% chance of their child inheriting the disease. There is also a 25% chance that their child will not inherit the mutated gene and will not develop CMT.
