Charcot-Marie-Tooth disease (CMT) is a progressive neuromuscular disorder that affects the peripheral nerves. CMT causes weakness and wasting of the muscles in the feet, legs, hands and arms. There is currently no cure for CMT, but there are ways to manage symptoms and slow progression of the disease.
What is CMT?
CMT is one of the most common inherited neurological disorders, affecting approximately 1 in 2,500 people in the United States. It is caused by mutations in genes that produce proteins involved in maintaining the health of the peripheral nerves. The peripheral nerves connect the brain and spinal cord to the muscles and sensory organs. In CMT, the peripheral nerves become damaged, disrupting communication between the nerves and the rest of the body.
There are several types of CMT, classified by the specific gene mutations involved:
| Type | Cause |
|---|---|
| CMT1 | Mutation in genes that maintain the myelin sheath around nerves |
| CMT2 | Mutation in genes involved in axon structure and function |
| CMT3 (Dejerine-Sottas disease) | Severe, early-onset form caused by mutations in myelin-related genes |
| CMT4 | Autosomal recessive inheritance caused by mutations in genes involved in axon stability and regeneration |
| CMTX | X-linked form caused by mutations in the GJB1 gene |
The most common forms are CMT1, which accounts for about 70-80% of cases, and CMT2, which accounts for 10-15% of cases. Over 100 gene mutations associated with CMT have been identified so far.
What are the symptoms of CMT?
The main symptoms of CMT include:
- Progressive muscle weakness and atrophy, usually beginning in the feet and legs
- Foot deformities like high arches and hammertoes
- Frequent tripping or falls
- Loss of muscle bulk in the lower legs
- Numbness or reduced ability to feel heat, cold and pain
- Balance problems
- Difficulty walking
- Fatigue
- Cramping
- Hand weakness and loss of fine motor skills
Symptoms begin subtly, usually in adolescence or early adulthood, but tend to worsen gradually over time. The progression rate and severity can vary significantly even among members of the same family.
How is CMT diagnosed?
There is no single test that can definitively diagnose CMT. It is diagnosed based on a combination of family history, genetic testing, and neurological exams and tests. Typical diagnostic steps include:
- Family history – Looking for patterns of nerve symptoms in parents, grandparents, siblings, aunts/uncles, and cousins.
- Physical exam – Checking for reduced reflexes, high arches, hammertoes, and muscle wasting in the lower legs.
- Nerve conduction studies – Measuring how fast electrical signals travel along the peripheral nerves.
- Electromyography – Evaluating and recording the electrical activity of muscles.
- Genetic testing – Analyzing genes known to be associated with CMT.
- Nerve biopsy – Removing and examining a small part of a nerve under a microscope.
MRIs or nerve ultrasound imaging may also be done to look for signs of nerve damage. The results of these various tests can help pinpoint the specific subtype of CMT.
What causes the nerves to degrade in CMT?
The peripheral nerves are made up of axons (long fibers that transmit signals) wrapped by myelin sheaths (an insulating layer). In CMT, mutations in genes affect either the axons themselves or the myelin sheaths surrounding them:
- Myelin-related CMT – Mutations cause errors in producing proteins needed to form and maintain the myelin sheath. This disrupts the signals traveling through the nerves.
- Axon-related CMT – Mutations affect proteins that support the structure and function of the axons. This causes the axons to deteriorate over time.
In both types, the degradation of axons and/or myelin leads to a breakdown in communication between the nerves and muscles. Nerve signals slow down or become disrupted, resulting in muscle weakness and wasting.
Is there a cure for CMT?
Unfortunately, there is currently no cure for CMT. Nerves cannot regenerate or heal themselves effectively once damaged. Researchers are investigating gene therapy, neuroregeneration treatments, and other innovative approaches, but these are not yet ready for clinical use.
However, the outlook for CMT continues to improve. Better diagnostic methods, supportive treatments, and assistive devices help manage symptoms and maintain quality of life. Increased research and clinical trials hold promise for future treatments to slow or stop progression.
Can you prevent CMT from getting worse?
While there is no cure, there are ways to help slow the progression of CMT, manage symptoms, and prevent complications. Some key strategies include:
Daily exercise
Physical activity can help maintain muscle strength, flexibility, balance and endurance. Recommended exercises for CMT include:
- Low-impact aerobics like swimming, cycling or elliptical training
- Stretching major muscle groups
- Strength training with resistance bands
- Balance exercises like heel-toe walking or standing on one leg
- Yoga and pilates to improve strength, balance and flexibility
Overexertion can worsen weakness, so sufficient rest between exercise sessions is important.
Orthotics
Orthotic devices like leg braces, custom shoes, and shoe inserts can provide support, improve gait and prevent deformities. Ankle-foot orthoses brace the foot and ankle to aid walking. Foot orthotics redistribute pressure to prevent calluses and sores.
Occupational therapy
Occupational therapists can recommend assistive devices and strategies to maintain your independence and prevent injuries. This may include tools to assist with gripping, reaching, cooking, dressing, and personal care.
Physical therapy
Physical therapists can develop an exercise program tailored to your abilities and limitations. They may use techniques like massage, heat/cold therapy, electrical stimulation, and assisted stretching to maintain range of motion and prevent muscle shortening.
Healthy diet
Eating a well-balanced diet helps prevent obesity and related health issues. Make sure to get sufficient protein, calcium, vitamin D, and antioxidants. Stay hydrated and limit alcohol intake.
Good posture and ergonomics
Use chairs, wrist supports, and devices that allow you to maintain proper spine alignment and minimize strain. Take frequent breaks when performing repetitive tasks.
Protect limbs and joints
Use caution to avoid falls, injuries, and putting excess stress on weakened limbs. Wear protective footwear and wrist guards. Change positions frequently and shift your weight while sitting or lying.
Avoid toxins
Exposure to toxins like mercury, arsenic, and lead can worsen nerve damage. Avoid sources like tainted fish and lead-glazed pottery. Don’t smoke and limit alcohol.
Manage diabetes
Diabetes and prediabetes are risk factors for peripheral neuropathy. Careful blood sugar control through diet, exercise, medication and monitoring helps protect nerve health.
Stimulate nerves
Emerging research shows gentle electrical nerve stimulation may help regenerate nerves and slow CMT progression. More studies are needed to confirm benefits.
What medications treat CMT?
There are no FDA-approved medications specifically for CMT. Approved treatments target symptomatic relief:
- Pain relievers – Over-the-counter pain medications or prescription options help manage neuropathic pain from nerve damage.
- Antidepressants – Certain tricyclic antidepressants like amitriptyline may reduce pain.
- Anti-seizure drugs – Medications including gabapentin and pregabalin can reduce pain related to nerve fiber damage.
- Physical therapy – Stretching, massage, and range-of-motion exercises keep muscles flexible and joints mobile.
- Muscle relaxants – Drugs like cyclobenzaprine relieve muscle tightness and cramping.
- Braces – Braces stabilize weakened joints to aid movement and prevent injury.
Talk to your doctor to determine which symptom management approaches are right for you. Be cautious with medications that cause fatigue or sedation, which may increase unsteadiness.
Are there any promising treatments being researched?
Active research is underway to find treatments to slow or stop the progression of CMT. Some emerging options undergoing trials include:
Gene therapy
Gene therapy aims to address the genetic mutations causing CMT. The approach involves using viruses modified to deliver healthy genes into nerve cells. Early stage trials are in progress.
Neuroregeneration drugs
Medications are being tested to stimulate nerve growth and regeneration. Preliminary research indicates PXT3003 may improve myelination and axon stability.
Stem cell therapy
Stem cells derived from adult tissues or umbilical cords are being studied as a way to regenerate damaged nerves. More evidence is still needed.
Exon skipping
For mutations that lead to abnormal protein production, exon skipping uses molecules called antisense oligonucleotides to block those changes. It is still experimental.
Exercise and rehabilitation
Controlled clinical trials are evaluating whether specific training programs like eccentric strengthening exercises or combination exercise/education approaches can slow CMT progression and improve mobility.
What is the long-term outlook for people with CMT?
CMT symptoms generally progress gradually over many years or decades. The long-term outlook depends on the type of CMT and other factors like age of onset, mutation severity, and overall health. For most people with CMT:
- Normal lifespan is possible with proper management of symptoms.
- Mobility aids like foot/leg braces, orthotics, and scooters allow maintaining independence.
- Hand tremors and dexterity problems may affect fine motor skills.
- Balance problems increase risk of falls later in life.
- Foot deformities may require surgery to maintain ability to walk.
- Cardiovascular fitness routines adapted to abilities help delay mobility decline.
Staying as active as possible and using assistive devices helps maintain quality of life. Seeking support through counseling or CMT organizations also aids coping.
Conclusion
Living with CMT presents many challenges, but the condition can be managed with various supportive treatments and lifestyle adaptations. Physical and occupational therapy, braces, orthotics, exercise programs and healthy habits all play important roles in maximizing mobility and independence. While more research is still needed to find a cure, increased understanding of CMT provides hope for emerging treatments that may slow progression in the future.