Causes of Charcot-Marie-Tooth Disease
Causes of Charcot-Marie-Tooth disease are genetic mutations that affect the peripheral nerves. There are many subtypes of CMT, each linked to a specific genetic mutation, but all involve damage to the peripheral nervous system. Understanding the causes of Charcot-Marie-Tooth disease is crucial for accurate diagnosis and potential future treatments.
1. Genetic Mutations
Charcot-Marie-Tooth disease is an inherited condition. Mutations in more than 100 genes have been associated with various forms of CMT. These genes are involved in the production of proteins essential for the structure and function of peripheral nerves.
Depending on the mutation, either the myelin sheath (the insulating layer surrounding nerves) or the axons (the long parts of nerve cells that transmit signals) are affected.
2. Inheritance Patterns
There are several inheritance patterns:
- Autosomal dominant: One copy of the mutated gene from either parent is enough to cause the disease (the most common form).
- Autosomal recessive: Two copies of the mutated gene, one from each parent, are needed.
- X-linked inheritance: The mutated gene is on the X chromosome, usually affecting males more severely.
If a parent has CMT, there’s a 50% chance of passing it to their child, depending on the type.
3. Subtypes of CMT
The two main types are:
- CMT1: Caused by damage to the myelin sheath. It includes CMT1A, the most common subtype, caused by a duplication of the PMP22 gene.
- CMT2: Caused by axonal damage, affecting the part of the nerve that transmits impulses.
Other less common types include CMTX (X-linked), CMT4 (autosomal recessive), and intermediate CMT, which has features of both types 1 and 2.
4. De Novo Mutations
In some rare cases, a person develops Charcot-Marie-Tooth disease due to a spontaneous mutation with no family history. These cases are referred to as de novo mutations.
5. Role of Nerve Degeneration
In all forms of CMT, the end result is that peripheral nerves fail to transmit signals effectively. This leads to muscle weakness, wasting, and loss of sensation — most commonly in the lower legs and feet, but also in the hands as the condition progresses.
While the causes of Charcot-Marie-Tooth disease are genetic, knowing the exact mutation can help guide treatment decisions, future planning, and family counselling.
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