Charcot-Marie-Tooth disease – genetic testing for CMT

Charcot-Marie-Tooth (CMT) is a genetic disorder that affects the peripheral nervous system. This is one of the most common inherited neurological diseases, with a prevalence of 36 per 100,000.

Symptoms of CMT begin to appear during childhood but may also appear at later stages of life. The disease is more common in men than in women. There is currently no known cure for CMT.



Types of CMT

There are many types of this disease, with different methods of classification. This article focuses on classification by inheritance pattern:

  • Autosomal dominant inheritance: CMT1 and CMT2 are two types of the disease with an autosomal dominant inheritance pattern. Each of these types includes several sub-types. The most prominent sub-type of CMT1 is called 1A. Other sub-types include 1C and 1B (considered less severe). CMT2 includes sub-types such as 2A and B2 and is considered less severe than CMT1.


  • Autosomal recessive inheritance: CMT4 is a severe form of the disease divided into sub-types such as CMT4A, characterized by an absence of myelin in the nerve fibers (Axons).


  • X-linked inheritance: there are five main types of this disease that are inherited from the mother, including CMTX1, CMTX2, CMTX3, CMTX4 and CMTX5.


What are the symptoms?

Since there are many types of CMT, it also has a wide range of clinical manifestations.

CMT1 symptoms can begin during childhood but in many cases appear between ages twenty and forty. The first symptoms include calves with an “inverted champagne bottle” appearance, highly arched feet, and foot drop.

CMT’s progression is usually slow, more symptoms develop gradually, but patients do not usually become wheelchair bound. Around eighty percent of patients suffer from CMT1.

More symptoms include:

  • Respiratory defects.
  • Hearing loss.
  • Vision impairments.
  • Numbness or tingling sensations in the limbs.
  • Difficulties swallowing, chewing, and speaking.
  • Areflexia (absence of reflexes).
  • Muscle and joint pain in the limbs.


What is the genetic cause for CMT?

In its common form (CMT1), the gene mutation is usually PMP22. However, fourteen different mutations that cause symptom onset have been discovered.

The different gene mutations cause a malfunction in protein production in the nerves. These disruptions are usually caused by damage to the myelin sheath that aids transmission of electric signals from the central nervous system to the organs.


How are CMT carriers diagnosed?

Gene mutations that cause the most common types of CMT can be detected rather easily after symptoms develop.

However, when discussing other types of gene mutations, a more thorough screening of all relevant genes is required, which is often expensive and time-consuming. When there is a family history of this disorder (when a family member has developed the disease), other family members can undergo genetic testing that screens for the relevant mutation.


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