Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathy (HMSN), is a common genetic neurological condition. It is characterized by symptoms of muscle weakness and numbness, particularly in the legs, resulting from damage to the peripheral nervous system.
The name “Charcot-Marie-Tooth” originates from the three physicians who first identified and described the disorder in 1886: Jean-Martin Charcot, Pierre Marie and Howard Henry Tooth.
CMT can be caused by several different gene mutations that lead to abnormal structure or function of the axon or myelin sheath of the peripheral nerve cells. The disease is classified into several types according to the causative gene.
CMT1 is caused by a mutation in PMP-22, P0, LITAF, EDFR or NEFL gene and affects the myelin sheath.
CMT2 is caused by a mutation in the mitofusin-2, RAB7, GARS, NEFL, HSP27 or HSP22 gene and affects the axon.
CMT3 is caused by a mutation in the P0 or PMP-22 gene and leads to severe symptoms resulting from damage to the myelin sheath.
CMT4 can be caused by a mutation in GDAP1, MEMR13, MYMR2, SH3TC2, NDG1, EGR2, PRX, FDG4 or FIG4 gene.
CMTX is caused by a mutation on the X chromosome.
The symptoms of CMT disease usually present between the ages of 5 and 15, although may differ according to the causative gene and specific case. They may include:
Muscle weakness in the limbs (e.g. feet, ankles, legs and hands)
Abnormal foot structure (e.g. high arches or flat feet)
Numbness or loss of sensation in the extremities
It is a progressive condition, which means that the symptoms are known to continually worsen over time.
The diagnosis of CMT disease begins with a discussion about the presenting symptoms, in addition to any family history of similar symptoms of CMT disease. A physical examination is then undertaken note any physical signs, such as foot deformation and muscle atrophy.
Further tests may include blood tests to screen for known gene mutations, a nerve conduction test, electromyography (EMG) or a nerve biopsy. Additionally, expectant parents that are known carriers of the genetic mutations can determine the genetic status of the child to decide whether to continue the pregnancy to full term.
There is no known cure for CMT disease and, instead, the aim of treatment is to reduce the symptoms and increase the quality of life of the individual.
The management of the condition may include physical therapy to help strengthen the muscles and prevent disease progression. Occupational therapy can help to identify areas that are difficult for patients and provide solutions, such as walking aids.
In some cases, surgery may be needed to correct deformation of the feet that prevent an individual from walking and moving independently. Pharmacotherapy may also be indicated to manage nociceptive or neuropathic pain.
It is important for affected individuals to have a strong support network that they can rely on when facing difficulties related to CMT disease. As it is a chronic and progressive condition, many individuals may find it difficult to stay positive and are more likely to face mental health issues.
In the United States, CMT affects approximately 125,000 people, which is about 1 per 2,500 people. The majority of those affected – about 70% - have CMT1 and the second most common type is CMTX.
In other countries, the prevalence of CMT disease is:
10.8 cases per 100,000 in Japan
17.5 cases per 100,000 in Italy
28.2 cases per 100,000 in Spain
Most patients with CMT have a normal life expectancy, but the quality of life can be impacted significantly, particularly as the disease progresses. This usually results from muscle weakness and foot deformities, which can inhibit the movement or other activities of an individual, reducing the ability to live independently.