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Causes

Charcot-Marie-Tooth disease (CMT) is caused by mutations (faults) in genes that cause the peripheral nerves to become damaged.

The peripheral nerves are a network of nerves that run from the brain and spinal cord (the central nervous system).

They carry impulses to and from the rest of the body, such as the limbs and organs, and are responsible for the body's senses and movements.

A peripheral nerve is similar to an electrical cable, and is made up of 2 parts:

  • the axon – which transmits electrical information between your brain and limbs, similar to the wiring in an electrical cable
  • the myelin sheath – which is wrapped around the axon to protect it and ensure the electrical signal is not broken, similar to the insulation around electrical cable

In some types of CMT, faulty genes cause the myelin sheath to break down.

Without protection, the axons become damaged, which affects the transmission of messages between the brain and the muscles and senses. This leads to muscle weakness and numbness.

In other types of CMT, the axons are directly affected and do not transmit electrical signals at the normal strength.

This means the muscles and senses do not get used enough, leading to symptoms of muscle weakness and numbness.

How CMT is inherited

A child with CMT may have inherited the genetic fault responsible for the condition from 1 or both parents.

No single faulty gene causes CMT. The many types of CMT are caused by different genetic mutations and the faulty genes can be inherited in several different ways.

Autosomal dominant

Autosomal dominant inheritance of CMT occurs when 1 copy of a mutated gene is enough to cause the condition.

If either parent carries a faulty gene, there's a 1 in 2 chance the condition will be passed on to each child they have.

Autosomal recessive

Autosomal recessive inheritance of CMT occurs when 2 copies of the defective gene are needed to cause the condition.

You inherit 1 copy from each parent. As your parents only have 1 copy of the gene, they don't develop CMT themselves.

If both you and your partner are carriers of the autosomal recessive CMT gene, there's a:

  • 1 in 4 chance each child you have will develop CMT
  • 1 in 2 chance each child you have will inherit 1 of the defective genes and be able to pass the condition to any children they have (known as being a carrier) – although they will not have any of the symptoms of CMT themselves
  • 1 in 4 chance each child you have will receive a pair of healthy genes and will not develop CMT

If only 1 parent has the autosomal recessive gene, your children will not develop CMT. But there's a 1 in 2 chance each child will be a carrier.

X-linked inheritance

In X-linked inheritance, the mutated gene is located on the X chromosome and passed from mother to son. Chromosomes are the parts of cells that carry your genes.

Men have XY sex chromosomes. They receive the X chromosome from their mother and the Y chromosome from their father.

Women have XX chromosomes. They receive 1 X chromosome from their mother and the other X chromosome from their father.

A woman with the defective X chromosome will usually have no or very mild symptoms because the other healthy X chromosome counters the effect of the defective one.

But there's a 1 in 2 chance she'll pass on the defective gene to her son and he'll develop CMT.

If a woman with the defective X chromosome only has daughters, CMT can skip a generation until one of her grandsons inherits it.

Types of CMT

There are many different types of CMT that are all caused by different mutations (changes) in your genes.

The main types of CMT are:

  • CMT 1 – the most common type, caused by defective genes that cause the myelin sheath to slowly break down
  • CMT 2 – a less common and usually less severe type than CMT 1, caused by defects in the axon
  • CMT 3 (Dejerine-Sottas syndrome) – a rare and severe type of CMT that affects the myelin sheath, causing severe muscle weakness and sensory problems to begin developing in early childhood
  • CMT 4 – another rare and severe type of CMT that affects the myelin sheath, which begins developing in early childhood and causes many people to eventually lose the ability to walk
  • CMT X – caused by a mutation in the X chromosome, and more common in men than women

You can read more about the classification of CMT on Charcot-Marie-Tooth UK.

Last Reviewed
07 October 2022
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14 Oxford Street,
Walsall,
West Midlands,
WS2 9HY
Company Registration: 07893857
Premises GPhC Number: 1038515
Superintendant: Bilal Shah (2061734)
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