Charcot-Marie-Tooth (CMT) disease refers to a set of genetically inherited neurological disorders that damage peripheral nerves, the essential pathways that link the brain and spinal cord with other parts of the body. As the most common genetically passed neuropathy, CMT is characterised by progressive nerve injury that may cause loss of sensation, tingling, chronic pain, muscle weakness, and deformities of the feet. 

Additionally, in some instances, the disorder can extend to autonomic nerves, thus causing problems with sweating and dizziness.

In this guide, we will break down the causes, symptoms, diagnostic approaches, and treatment options for Charcot-Marie-Tooth disease. Read on for a comprehensive overview!

What is Charcot-Marie-Tooth Disease?

Charcot-Marie-Tooth disease, also called hereditary motor and sensory neuropathy, is an inherited condition that causes progressive damage primarily to the peripheral nerves in the arms and legs, leading to smaller, weaker muscles, difficulty walking, loss of sensation, and common foot issues like high arches.

Charcot (shahr-KOH)-Marie-Tooth disease pertains to the group of inherited disorders that result in nerve damage. Primarily, this damage is exhibited in the nerves of the extremities, i.e., the peripheral nerves. Besides that, Charcot-Marie-Tooth disease is known as hereditary motor and sensory neuropathy.

This disease leads to the gradual shrinking of muscles and their weakening. In addition, it can make walking difficult and result in numbness of the legs and feet. There are people who lose the ability to tense their muscles. Hamstrings and high arches are very common foot problems that arise. The manifestations of the disease usually start in the feet and legs. However, in the long run, the symptoms may extend to the hands and arms.

Additionally, a majority of people with Charcot-Marie-Tooth disease exhibit symptoms during their teenage years or early adulthood. However, the onset of symptoms can also be in the middle of life or even in toddlers.

What are the Causes of Charcot-Marie-Tooth Disease?

CMT is caused by inherited gene mutations, with over 100 gene changes linked to the condition, which are passed down through autosomal dominant, autosomal recessive, or X-linked patterns, resulting in peripheral nerve damage through either the loss of the protective myelin sheath (demyelination) or the shrinking of the axon.

Gene changes are the cause of CMT. It might be a change of one gene or several genes. More than 100 gene changes have been associated with the condition. Hence, it has a large number of different types. The gene change(s) are inherited from the biological parent(s). The categories of inheritance patterns are:

• Autosomal Recessive: Both parents have to carry the altered gene to be able to pass it on.
• Autosomal Dominant: Only one parent with the altered gene is enough to pass it on. Every child has a 50% chance of getting it.
• X-linked: The altered gene is on the X chromosome. Males usually have more severe symptoms because they have only one X chromosome.

In the case of CMT, the gene changes interfere with the cells (neurons) of peripheral nerves in one or both of the following ways:

• Myelin Loss: The myelin sheath is a protective cover that surrounds a part of a nerve cell. CMT can bring about too little or total myelin absence. This slows the nerve signal transmission speed. In such cases, CMT is a demyelinating disease.
• Axon Damage: The axon is that part of a neuron that converts electrical signals into chemical ones. CMT can cause the shrinking or wasting away of the axons. Thus, the signals that come and go are weakened.

What are the Risk Factors of Charcot-Marie-Tooth Disease?

As CMT is a hereditary disease passed through genes, the key risk factors include having a family history of the disorder, with symptoms typically beginning in adolescence or early adulthood, although onset can occur at any age.

Charcot-Marie-Tooth disease is a hereditary disease. That means it passes from parents to children through genes. The significant risk factors are as follows:

• Age: Usually, the onset of symptoms is in the teenage years or early adulthood, though they are capable of showing up at any age.
• Gender: Both male and female are equally prone to the disease; however, some specific types may demonstrate gender bias.
• Geographic Location: The prevalence of certain CMT types is higher in specific populations, for example, those of Northern European descent.
• Family History: Having a family history of CMT makes you more likely to be affected by the disease.

What are the Symptoms of Charcot-Marie-Tooth Disease?

Symptoms of CMT, which vary in severity, often begin in adolescence or early adulthood, including muscle weakness and wasting in the feet and lower legs, loss of sensation in the limbs, and foot abnormalities like hammer toes and high arches, which can lead to problems with balance and gait.

The symptoms of Charcot-Marie-Tooth disease most commonly become apparent in adolescence or early adulthood. Primary symptoms of the disease are:

• Muscle weakness and atrophy that initially involve the foot, lower leg, hand, and forearm
• Sensory loss in the fingers, toes, and limbs

Moreover, the individual may experience other symptoms like:

• Malformations of the foot muscles resulting in high arches and hammer toes
• Difficulties in using the hands
• Unsteady ankles and problems with balancing
• Cramping in the lower legs and forearms
• Partial loss of vision and hearing
• Scoliosis
• Reduced reflexes

The symptoms and their severity can be very different from one person to another and even between close relatives who have inherited the same condition. In fact, because the symptoms are so subtle, it is pretty standard that people do not recognise that they have CMT in the early stages of the disease.

Symptoms in Children

If symptoms appear during childhood, the child may:

• Be clumsier than their peers and more prone to accidents
• Show an abnormal gait due to difficulty in lifting the feet from the ground with each step
• Having the feet drop forward while lifting the feet

Most of the other symptoms emerge when the child goes through puberty and then moves to adulthood, but can be present at any age, from very young children to those in their late 70s. 

Eventually, the leg may even undergo a transformation where the part below the knee becomes extremely skinny, while the thighs still have the normal muscles of volume and shape.

The symptoms, which have a tendency to become worse with time, may include:

• The hands and arms are becoming weaker
• Lessening of the ability to use the hands, for instance, doing up buttons or opening jars and bottle caps
• Muscle and joint pain as a result of walking and posture problems, which place a strain on the body
• Neuropathic pain caused by damaged nerves
• Difficulties with walking and mobility, especially among the elderly

Supportive devices might include a wheelchair, a leg brace, certain types of shoes, or other orthopaedic devices.

What is the Diagnosis of Charcot-Marie-Tooth Disease?

The diagnosis of CMT involves a medical history and physical exam, which are supported by tests such as nerve conduction studies and electromyography to assess nerve function, with genetic testing or a nerve biopsy often used to confirm the specific type of nerve damage and gene mutation.

When diagnosing Charcot-Marie-Tooth disease, the doctor initially gathers information about the patient’s medical history and performs a physical examination to identify the symptoms of the disease.

Tests that can indicate to your doctor the cause and severity of the nerve damage include the following:

• Nerve Conduction Studies: These tests measure the strength and speed of the signals sent through the nerves. Small electric shocks delivered by electrodes put on the skin stimulate the nerve. If the response is slow or weak, it may indicate a nerve disorder such as Charcot-Marie-Tooth disease.
• Electromyography: This is also known as EMG. A thin needle electrode is put through the skin into a muscle by a healthcare professional. The test measures electrical activity when the muscle is relaxed and when it is slightly tightened by the patient. This might assist in determining the muscles that are affected by the condition.
• Nerve Biopsy: A doctor removes a small piece of peripheral nerve from the back of the lower leg after cutting through the skin. The nerve sample is sent to the lab for testing to determine the cause of the nerve condition.
• Genetic Testing: A blood sample is taken from the individual and is tested in the laboratory for common gene changes associated with Charcot-Marie-Tooth disease. Genetic testing might be helpful to those who suffer from the disease and want to plan their families. Besides that, a gene test can also rule out other sources of nerve damage. A genetic counsellor can provide information and support regarding the test.

What is the Treatment of Charcot-Marie-Tooth Disease?

While there is currently no cure for CMT, treatment focuses on relieving symptoms and maintaining mobility through physical and occupational therapy, pain management using medications like NSAIDs or TCAs, and the use of assistive devices like braces, splints, or orthopaedic shoes.

Currently, there is no cure for CMT. However, treatments may alleviate symptoms and curb the onset of physical impairments:

• Non-steroidal anti-inflammatory medications (NSAIDs) like ibuprofen can be used to relieve joint and muscle pains and also pain due to nerve damage.
• In a case where NSAIDs do not relieve the symptoms, the doctor may prescribe Tricyclic antidepressants (TCAs). Commonly used to treat depression, TCAs may help in neuropathic pain reduction. Nevertheless, they may have some side effects.
• By means of low-impact and gentle exercises, physical therapy helps not only to strengthen but also to stretch muscles. It can be very effective in muscle retention for an extended time period as well as in the prevention of muscle contracture.
• Occupational therapy can be a transforming factor for patients struggling with finger movement and grip strength, helping them regain control over everyday tasks that once felt frustrating or nearly impossible.
• Assistive devices like specific orthopaedic devices, braces, or splints can be of help to the person in keeping the ability to move around and also in preventing injuries. Ankle support can be provided by high-top shoes or special boots, while certain types of shoes or shoe inserts can facilitate walking. For perfect hand coordination, thumb splints can be of assistance.
• Cognitive behavioural therapy (CBT) may be helpful to CMT patients in managing everyday-life issues better and, if necessary, coping with depression as well.
• In some cases, foot pain may be relieved and walking made easier through surgery to fuse bones in the feet or remove a part of a tendon. Surgery not only can correct flat feet but also can relieve joint pain and correct heel deformities.
• If a patient develops scoliosis or curvature of the spine, they might be recommended to wear a back brace, and in some instances, surgery may be required as well.

What are the Complications of Charcot-Marie-Tooth Disease?

If left untreated, the progressive muscle weakness associated with CMT can lead to severe disability and significant mobility challenges, as well as chronic foot ulcers and deformities, which may also result in a psychosocial impact such as anxiety and depression.

If Charcot-Marie-Tooth disease is left untreated or not properly managed, it can give rise to several serious complications:

• Severe Disability: Ongoing muscle weakness may gradually limit mobility, making independent movement increasingly difficult.
• Foot Ulcers and Deformities: Abnormal foot structure and poor mechanics can cause skin breakdown, persistent ulcers, and infections.
• Psychosocial Impact: Living with a chronic, progressive condition can affect emotional well-being, often contributing to anxiety, depression, and feelings of social withdrawal.

Short-Term and Long-Term Complications

The short-term complications of the disease may consist of falling and getting hurt due to muscle weakness. On the other hand, long-term complications can be chronic pain, severe disabilities, and the need for devices such as walking sticks.

FAQs about CMT

1. Does the Charcot-Marie-Tooth affect the heart?

Peripheral muscle atrophy is the main characteristic of Charcot-Marie-Tooth disease (peroneal muscular atrophy). In this condition, cardiac arrhythmias and conduction disturbances have been observed.

2. Is CMT genetic or hereditary?

Yes, CMT is both genetic and hereditary, caused by mutations in the genes that control peripheral nerve function. A child may inherit the faulty gene from one or both parents, and there is no single gene responsible for all types of CMT.

3. Can CMT affect the kidneys?

In case the person is affected by CMTDIE, which is a subtype of CMT, it can lead to issues in the kidneys. Thus, for CMTDIE patients, doctors always recommend regular proteinuria testing and follow-up with a kidney specialist in case of elevated urine protein levels. 

4. What are the early signs of CMT?

Primary symptoms of CMT:

• Muscle weakness in the feet, ankles, and legs at first
• Extremely high arches of the feet, which can make the ankle unstable, or very flat feet
• Curling of one’s toes (hammer toes)
• Not being able to walk properly because of the weakness of the ankle muscles, which results in a weird or high step

5. What can make CMT worse?

Certain medications that are referred to as neurotoxic drugs may injure the peripheral nerves and cause the symptoms of individuals with CMT to become worse. Such drugs can speed up nerve damage; hence, muscle weakness may become more severe, loss of sensation can occur, or other complications may develop.

Conclusion

To sum up, Charcot-Marie-Tooth disease (CMT) is a neurological disorder that affects the peripheral nerves and eventually causes the muscles to weaken, the sensation to be lost, and coordination to be decreased. Besides these, the diagnosis of CMT is based on clinical presentation, family history, and genetic testing. 

But still, no cure for CMT exists, though treatment options, which include therapy, orthopaedic interventions, and pain management strategies, can be undertaken. The prognosis of CMT depends on various factors, such as the seriousness of symptoms, the age at which the disease occurs, and the genetic subtype. However, with good management and support, people with CMT can live a fulfilling life.

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