The different types of Charcot-Marie-Tooth (CMT)

Charcot-Marie-Tooth (CMT) is not a single condition, but a group of inherited nerve disorders.

There are different types of CMT, and the main difference comes down to which part of the nerve is affected.
In some forms, the nerve fiber itself, the axon, is damaged. In others, it is the protective layer around the nerve, called myelin.

Even though the types are different, many people experience similar core symptoms, such as:

• muscle weakness in the feet and legs
• balance problems or frequent tripping
• numbness or reduced sensitivity
• changes in foot shape, like high arches or claw toes

At the same time, the different types can vary quite a bit, especially when it comes to progression, inheritance, and the underlying genetics.

In CMT1, the myelin sheath is affected. This is the protective layer that helps electrical signals travel along the nerves.

When myelin is damaged, signals are transmitted more slowly.

Typical characteristics:

• symptoms often start in adolescence or early adulthood
• weakness and muscle loss in the lower legs
• reduced reflexes and slowed nerve conduction

The most common subtype is CMT1A, caused by a change in the PMP22 gene.
It is considered the most common form of CMT.

Inheritance: usually autosomal dominant

The myelin layer is usually still intact, but the signal itself becomes weaker and less reliable.

Typical characteristics:

• often starts a bit later, from teenage years to adulthood
• weakness in the feet and legs, and later in the hands
• numbness or reduced vibration sense
• often a slower progression compared to CMT1

There are several subtypes, including:

• CMT2A (linked to the MFN2 gene)
• CMT2E, CMT2F, CMT2K and others

Inheritance: often autosomal dominant, sometimes recessive

CMT4 includes several rare forms that are usually inherited in a recessive way.

This means both parents carry the gene, even if they do not have symptoms themselves.

Typical characteristics:

• often starts in childhood
• can progress faster in some cases
• more noticeable foot deformities
• in some cases, people may need orthoses or a wheelchair over time

Examples include CMT4A, CMT4B1, and CMT4C.

In CMTX, the genetic change is located on the X chromosome.

Because men only have one X chromosome, they are usually more affected.
Women can carry the gene and often have milder symptoms, or sometimes none at all.

Typical characteristics:

• often starts in childhood or teenage years
• weakness in the legs and hands
• possible sensory issues or balance problems

The most common form is CMTX1, linked to the GJB1 gene.

Besides the main types, there are also some less common or related conditions.

HNPP (Hereditary Neuropathy with Liability to Pressure Palsies)
This condition is linked to changes in the PMP22 gene and makes nerves more sensitive to pressure.

CMT with SORD mutation
This is a more recently discovered subtype and is currently being researched, including potential treatment approaches.

These examples show how complex the genetic background of CMT can be.

That is why genetic testing is so important. It helps identify the exact type and can guide treatment decisions.

Whether it is CMT1, CMT2, CMT4 or CMTX, all types belong to the same group of conditions that affect the nerves.

Understanding the specific type can make a real difference.
It helps doctors estimate progression and choose the right kind of support.

And honestly, the more you understand your specific type, the easier it often becomes to find your own way of dealing with CMT in everyday life.