Charcot–Marie–Tooth disease (CMT) is a neurological disorder affecting the peripheral nerves. Peripheral nerves act as a connection between the central nervous system (CNS), which includes the brain and spinal cord, and the rest of the body.
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The main function of these nerves is to regulate the sensory and motor functions, and hence, an individual diagnosed with CMT has abnormal sensory and motor functions. CMT results due to certain gene alterations and is also named as hereditary motor and sensory neuropathy (HMSN) or peroneal muscular atrophy.
Charcot–Marie–Tooth disease is named after three scientists - Jean-Martin Charcot, Pierre Marie, and Howard Henry Tooth - who identified CMT in 1886. CMT occurs either due to the defect in the nerve axon or due to the damage to the myelin sheath layering the axons, thereby resulting in cessation of the electrical signals transmitted by the nerves.
Causes of Charcot–Marie–Tooth Disease
Charcot–Marie–Tooth disease can be inherited in an autosomal recessive, autosomal dominant, or X-linked dominant fashion.
- If one copy of an atypical gene is inherited for an autosomal recessive disorder, the person with this single gene copy will not be affected. This person will be a carrier of the disease. If two carriers have a child that inherits a copy of a recessive gene from each parent, the child will develop CMT and its symptoms. If two potential carriers plan to have a child, each new pregnancy has a 25% chance of having a child affected by CMT, a 50% chance of having a child who is a carrier of the disease, and a 25% chance of having a child who has no copies of the gene.
- If one abnormal gene alone can cause the disease, it is referred to as an autosomal dominant genetic abnormality. In such a situation, the dominant gene responsible for disease transmission is acquired from either of the parents or maybe the consequence of novel genetic mutation in the body. With each pregnancy, the chances of transmitting the disease become 50% irrespective of the sex of the ensuing child.
- Under the X-linked genetic abnormality, the defective gene is located on the X chromosome. Both males and females can be affected by this form of gene abnormality (females have two X genes and males have one X and one Y gene). However, affected males will have a more acute presentation because they only have a single X chromosome.
Which genetic mutations may result in Charcot–Marie–Tooth disease?
Charcot–Marie–Tooth disease is categorized into various types according to the type of genetic mutations. Below is a list of various genetic mutations that are responsible for causing various forms of CMT:
- Mutation of PMP-22, P0, LITAF, EDFR, or NEFL genes can result in CMT, which leads to the destruction of the myelin sheath. This form of CMT is known as CMT1.
- Injury to the axons can result from the mutation in the mitofusin-2, RAB7, GARS, NEFL, HSP27, or HSP22 gene. This form of mutation results in damage to the axons and is categorized as CMT2.
- Alterations in the P0 or PMP-22 gene results in an acute and rapid onset of the symptoms; these sets of mutations are categorized under CMT3.
- CMT4 results from the mutations of GDAP1, MEMR13, MYMR2, SH3TC2, NDG1, EGR2, PRX, FDG4, or FIG4 gene, whereas alterations in the X chromosome results in CMTX.
What are the symptoms of Charcot-Marie-Tooth disease?
Both motor and sensory nerves are affected by Charcot–Marie–Tooth disease, which affects activities like food ingestion, inhalation, walking, and speaking. Early symptoms of CMT usually manifest in early adolescence; however, it may begin in early or during later part of the adult life.
Initially, the longest nerve fibers are affected. Those fibers generally are those of the arms, hands, legs, and feet. Affected individuals may feel limited sensitivity upon touching hot items or may feel weakness in upper and lower limbs. One may even lose sensitivity to touch or may not even feel pain. Some other symptoms are:
- Difficulty in performing fine motor skills like writing
- High-stepped gait referred to as foot drop
- Loss of muscle mass of the lower extremities
- Lack of body balance and coordination resulting in frequent falls
- Elevated foot arch and flat feet
CMT is a slowly progressing disease, and the affected person may lead a normal life for many years. However, occasionally, CMT may affect the respiratory muscles, which can become fatal.
Who is at risk of Charcot–Marie–Tooth disease?
Both men and women are affected by Charcot–Marie–Tooth disease. The early symptoms of CMT may start in teens or in early adulthood or during the middle years of life. However, CMT may remain unidentified, wrongly diagnosed, or may get diagnosed at advanced stages; hence, the actual number of affected people may even be greater than available statistics. Currently, more than 250,000 Americans are affected by CMT.
How is Charcot–Marie–Tooth diseasediagnosed?
Physicians usually start the diagnosis of Charcot–Marie–Tooth disease by questioning the medical and family history, which may indicate the extent and type of symptoms.
Furthermore, a physician may conduct certain neurological tests to identify muscle weakness, loss of muscle mass, abnormal tendon reflexes, and loss of sensation in both the upper and lower extremities. Some typical symptoms like high foot arch, hammertoe, flat feet, or upturned feet may direct toward CMT.
One typical sign that is usually present in CMT1 is the elongation of nerves that may, at times, be visible or may be palpable through the skin. These elongated nerves are referred to as hypertrophic nerves, which result due to the thickening of the myelin sheaths. Some other electrodiagnostic tests to confirm CMT are:
Nerve conduction tests: Electrodes are placed over the skin and transmit mild electric shocks for nerve arousal. An abnormal electric impulse may reveal CMT.
Electromyography (EMG): A fine needle electrode is introduced to the muscle via the skin. Electric activity is then determined through relaxing and tightening the muscle.
Biopsy of the nerve: A small portion of a peripheral nerve is removed from the calf muscle and is analyzed in the laboratory to differentiate CMT from other nerve disorders.
Genetic Testing: Genetic tests may be conducted either via blood or saliva. A positive genetic test is a confirmatory marker of CMT; however, a negative test does not rule out the possibility of CMT as some forms of CMT may remain undiagnosed even via genetic testing.
Is Charcot–Marie–Tooth disease a curable disease?
Currently, there is no cure for Charcot–Marie–Tooth disease; however, various therapies like physiotherapy, occupational therapy, orthopedic surgery, and application of orthopedic braces and devices have been found helpful in alleviating disabling symptoms associated with CMT. In some cases, pain killers are also prescribed if the condition turns painful in some patients.
Are there any self-help tips to manage Charcot–Marie–Tooth disease?
Although it is not possible to regain the atrophied muscles, the best strategy remains to strengthen the unaffected muscles. Alternative therapies, like tailored physiotherapy programs, are also designed to reinforce strength and flexibility.
Physicians recommend moderate exercise; however, overexertion is discouraged to prevent any further damage. Some exercises which are less strenuous and are usually advisable are:
- Mild to moderate walking with poles
- yoga and Taichi
Some other tips which can help in managing Charcot–Marie–Tooth disease are:
- Wearing tailored shoes- Individuals affected with CMT usually come across difficulty in finding appropriate shoes because of hammered toes or high-arched feet. Patients and caregivers should look for stores with professional pedorthists who are trained to fabricate shoes that prevent disabling or painful conditions of the foot or ankle
- Sensory loss in lower extremities is one of the symptoms in affected patients; hence they must visit a good podiatrist for filing nails or to get rid of the hard skin under the feet
- Patients may also experience hearing loss, as the cochlear nerve may also be affected by CMT. Regular ear examination by an ENT (Eyes nose and throat) specialist helps in identifying such concerns at the earliest. Doctors may prescribe hearing aids for a better hearing capacity.
- In rare cases, CMT patients may suffer from sleep apnea, which may result due to the hindrance of the upper airway. Upon diagnosis, a physician may advise devices such as continuous positive airway pressure (CPAP) masks
- CMT may also result in vocal cord paralysis resulting in difficulty in producing voice while speaking. Timely consultation with an ENT specialist can help in early diagnosis and treatment
- CMT patients must consult a physician before taking any course of medication for any condition. Certain medications like taxols are known to impart neurotoxic effects; hence, it is imperative to consult a physician prior to initiating a therapy
- An orthopedic consultation can help in alleviating gait problems associated with CMT. An orthopedic surgeon may recommend assistive devices like ankle-foot orthoses (AFOs), which aid in supporting the feet in the right position, thereby helping in relieving gait problems.