Autosomal dominant demyelinating Charcot-Marie-Tooth disease is a long-term nerve disease that mainly damages the peripheral nerves, which are the nerves outside the brain and spinal cord. In this condition, the myelin sheath, the “insulation” around the nerve fibers, is damaged. This slows down the speed of the electrical signal in the nerve. Because the nerves to the feet and hands are longest, problems usually start there first, causing weakness and loss of feeling in the legs, feet, hands, and sometimes arms.NCBI+1
Autosomal dominant demyelinating Charcot-Marie-Tooth disease (often called CMT1) is a genetic nerve disease. “Autosomal dominant” means a person usually needs only one changed (mutated) copy of the gene from one parent to develop the condition. “Demyelinating” means the problem is mainly in the myelin, the insulating coat that wraps around nerves and helps signals travel quickly. In CMT1, the myelin in the peripheral nerves (nerves to the feet, legs, hands and arms) becomes damaged and thinner, so messages between the brain, spinal cord and muscles slow down. People often notice weakness of the feet and legs, high arches, “hammer” or claw toes, tripping, balance problems and sometimes hand weakness. Sensation can be reduced, so the person may not feel pain or temperature properly in the feet and hands. The most common form, CMT1A, is often caused by extra copies of a gene called PMP22. There is no cure yet, but many treatments can help symptoms and quality of life. NINDS+2National Organization for Rare Disorders+2
The term “autosomal dominant” describes how the condition is passed in families. “Autosomal” means the gene change is on one of the non-sex chromosomes, so it affects people of any sex. “Dominant” means that a person only needs one copy of the changed gene (from one parent) to develop the disease. If a parent has this disease, each child has a 50% chance to inherit the gene change.NCBI+1
This autosomal dominant demyelinating group is usually called Charcot-Marie-Tooth disease type 1 (CMT1). It is the most common type of CMT and accounts for more than half of all CMT cases. Symptoms often begin in childhood or teenage years and slowly get worse over many years, but the speed and severity can be different from one person to another, even inside the same family.NCBI+2Charcot-Marie-Tooth Association+2
Other names and main types
This condition has several other names that doctors and scientists may use. It is helpful to know them because they may appear in medical reports or research papers. Common other names include:
Charcot-Marie-Tooth disease type 1 (CMT1) – the usual name for the autosomal dominant demyelinating form.Charcot-Marie-Tooth Association+1
Autosomal dominant demyelinating CMT – a descriptive name that highlights both inheritance pattern and myelin damage.SciSpace+1
Hereditary motor and sensory neuropathy type I (HMSN I) – an older name meaning an inherited disease affecting movement and feeling.NCBI+1
Within this group, there are several genetic types (subtypes). Each type is linked to a different gene:
CMT1A – caused by a duplication (extra copy) of the PMP22 gene on chromosome 17; this is the most common form.Genetic Diseases Center+2CMT Research Foundation+2
CMT1B – caused by changes (mutations) in the MPZ (P0) gene, which also codes for an important myelin protein.NCBI+1
CMT1C – linked to mutations in the LITAF (SIMPLE) gene, affecting myelin-forming Schwann cells.SciSpace+1
CMT1D – caused by mutations in the EGR2 gene, which helps control myelin-related genes.SciSpace+1
CMT1E – caused by point mutations in PMP22, rather than duplication; this can lead to more variable or severe demyelinating neuropathy.Balkan Medical Journal+1
Other rarer autosomal dominant demyelinating types (sometimes named CMT1F, CMT1G, CMT1H, CMT1I, etc.) involve mutations in additional genes discovered in more recent genetic studies.KoreaMed Synapse+1
Causes
In this disease, the main cause is a change (mutation) in certain genes that are important for the myelin sheath of peripheral nerves. Each “cause” below is one kind of genetic or related factor.
PMP22 gene duplication (CMT1A)
The most common cause is having an extra copy of the PMP22 gene on chromosome 17. This duplication leads to too much PMP22 protein in Schwann cells (myelin-forming cells). The extra protein upsets normal myelin structure, so the protective covering around nerves becomes unstable and thin, slowing nerve signals.Genetic Diseases Center+2CMT Research Foundation+2PMP22 point mutations (CMT1E)
Some people have a single letter change in the PMP22 gene instead of duplication. These point mutations can change the shape or behavior of the protein, causing abnormal myelin and a demyelinating neuropathy.Balkan Medical Journal+1MPZ (P0) gene mutations (CMT1B)
Mutations in the MPZ gene affect myelin protein zero, a key structural protein that holds myelin layers together. Faulty MPZ protein makes myelin weak and unstable, which leads to slow conduction and nerve damage in an autosomal dominant pattern.NCBI+2Wiley Online Library+2LITAF gene mutations (CMT1C)
Changes in the LITAF (SIMPLE) gene disturb protein handling inside Schwann cells. Mismanaged proteins can stress or damage these cells, causing poor myelin maintenance and demyelination.SciSpace+1EGR2 gene mutations (CMT1D)
The EGR2 gene is a transcription factor that turns on many myelin-related genes. Mutations here can switch these genes on or off in a harmful way, so Schwann cells cannot make normal myelin, leading to a demyelinating neuropathy.SciSpace+1NEFL gene mutations with demyelinating pattern
Some mutations in NEFL, a gene for neurofilament light chain, can show up with nerve conduction speeds in the demyelinating range, and be grouped with autosomal dominant demyelinating forms. The abnormal neurofilaments disturb the axon and its myelin covering.SciSpace+1Other myelin-related gene mutations
Research continues to find more genes in myelin production and maintenance that, when mutated, can cause autosomal dominant demyelinating CMT, often labeled with newer CMT1 subtype names.KoreaMed Synapse+1New (de novo) mutations
Sometimes the gene change is new in the affected person and is not seen in the parents. This is called a de novo mutation. Once present, it can then be passed in an autosomal dominant way to the next generation.NCBI+1Positive family history of CMT1
Having a parent or close relative with CMT1 strongly increases the chance of carrying the same gene mutation. This is not a separate biological cause but is a strong risk marker showing autosomal dominant inheritance.NCBI+1Errors during DNA copying in sperm or egg cells
Small random mistakes can occur when DNA is copied in sperm or egg cells. If these errors hit a myelin gene such as PMP22 or MPZ, they can create a disease-causing mutation that leads to autosomal dominant demyelinating CMT.ClinicalTrials.gov+1Unequal crossing-over in chromosome 17 (PMP22 region)
CMT1A duplication often happens because of an “unequal crossover” event during meiosis, where parts of chromosome 17 are mis-aligned and duplicated. This mechanical error in chromosome exchange produces the extra PMP22 copy.CMT Research Foundation+1Founder mutations in certain populations
In some regions or ethnic groups, one ancient mutation in a CMT1 gene has been passed down through many generations. This “founder effect” can make certain autosomal dominant demyelinating CMT types more common in that group.KoreaMed Synapse+1Reduced ability of Schwann cells to handle misfolded proteins
Many mutations cause myelin proteins to fold incorrectly. When Schwann cells cannot clear these abnormal proteins, they become stressed and may die or lose function, which leads to demyelination.Wikipedia+1Disrupted signaling pathways inside Schwann cells
Some mutations disturb key cell signaling pathways that guide myelin growth and repair. This can stop Schwann cells from wrapping the axon properly, causing thin or absent myelin.Wikipedia+1Secondary axonal damage due to long-standing demyelination
Although the primary problem is myelin, ongoing demyelination leads to secondary axonal injury. Over time the axon shrinks and degenerates, worsening weakness and sensory loss.NCBI+1Mitochondrial stress inside Schwann cells
Some CMT-related mutations affect how energy is made or used in nerve or Schwann cells. Low energy and high oxidative stress can damage both myelin and axons, worsening the demyelinating process.Wikipedia+1Genetic modifiers that change disease severity
Other genes, not directly causing CMT1, may modify how severe the disease becomes. They may affect myelin repair, inflammation, or nerve growth, and can partly explain why symptoms differ among people with the same core mutation.KoreaMed Synapse+1Epigenetic changes affecting myelin genes
Chemical marks on DNA or histones can change how strongly myelin genes are turned on or off. In some people, such epigenetic changes may worsen the effect of a CMT1 mutation or influence age at onset.KoreaMed Synapse+1Co-existing medical conditions that stress nerves
Diseases like diabetes, severe vitamin deficiency, or long-term kidney failure do not cause the CMT1 gene change but can further injure already vulnerable nerves, making the demyelinating neuropathy more noticeable.NCBI+1Neurotoxic drugs superimposed on a CMT1 mutation
Certain chemotherapy drugs or other strong neurotoxic medicines can worsen nerve damage in someone who already has an autosomal dominant demyelinating CMT mutation, even though they are not the primary genetic cause.NCBI+1
Symptoms
The symptoms usually start in the feet and legs and progress slowly. Not every person has every symptom, and severity can vary a lot.
Weakness in feet and ankles
People often notice trouble lifting the front of the foot or standing on tiptoe. This happens because the peripheral nerves that control the lower-leg muscles are damaged, so the muscles cannot contract strongly.Cleveland Clinic+2Mayo Clinic+2Muscle wasting in lower legs
Over time the calf and shin muscles become thin. The legs can look like an “inverted champagne bottle” (thin below, wider above), which is a classic feature of CMT1.Mayo Clinic+1Foot deformities (high arches and hammertoes)
Many people develop high arches (pes cavus) and curled toes (hammertoes). The imbalance between weak and strong muscles pulls the bones into these abnormal positions.Cleveland Clinic+2Mayo Clinic+2Foot drop and tripping
Weakness of the muscles that lift the front of the foot causes foot drop, so the toes drag on the ground. This often leads to tripping, stumbling, and frequent ankle sprains.Cleveland Clinic+1Difficulty running or walking fast
Running, climbing stairs, or walking on uneven ground becomes hard because of weakness, poor balance, and reduced ankle control. Children may be slower than peers in sports or playground activities.Cleveland Clinic+1Loss of feeling in feet and legs
People may feel numbness, tingling, or a “pins and needles” sensation, especially in the toes and soles. This is due to damage to sensory nerve fibers that carry touch and pain signals to the brain.Cleveland Clinic+2Mayo Clinic+2Poor balance and unsteady gait
Because both muscle strength and sensation (especially position sense) are reduced, it is hard to keep balance, especially in the dark or on uneven surfaces. The walking pattern may look awkward or clumsy.Cleveland Clinic+1Weakness and wasting in hands
Later in the disease, the hands may become weak and thin. Fine tasks like buttoning clothes, writing, or opening jars become more difficult as the small muscles of the hands lose nerve supply.Cleveland Clinic+2NCBI+2Loss of feeling in hands
Numbness or tingling can spread to the fingers. People may drop objects because they cannot feel them well, or may not feel pain from small cuts or burns on the hands.Cleveland Clinic+1Reduced or absent reflexes
Reflexes, such as the ankle jerk, are often weak or absent when tested by a doctor with a reflex hammer. This reflects the loss of normal nerve-muscle communication in the reflex arc.NCBI+1Leg and foot pain
Some people have burning, shooting, or aching pain in the feet or legs due to damaged sensory nerves. Others may feel muscle cramps after walking or standing.Cleveland Clinic+1Fatigue with activity
Because muscles are weak and nerve signals are slow, walking or standing for long periods is tiring. People may need frequent rests or may use walking aids over time.Cleveland Clinic+1Spinal curvature (scoliosis)
Some patients, especially those with early onset disease, can develop side-to-side curvature of the spine. This occurs due to long-term muscle imbalance along the trunk.NCBI+1Tremor
A fine shaking of the hands (postural tremor) may be seen in some CMT1 families, sometimes described as part of the “Roussy-Lévy” variant. This tremor comes from combined nerve and muscle involvement.NCBI+1Mild hearing or breathing problems in some cases
Rarely, other nerves such as those to the ears or breathing muscles can be affected, causing hearing loss or shortness of breath, especially in more severe genetic subtypes.NCBI+1
Diagnostic tests
Doctors diagnose autosomal dominant demyelinating CMT mainly by history, family pattern, examination, and nerve tests. Genetic tests confirm the specific type. Tests can be grouped as requested.
Physical exam–focused tests
General neurological examination
The doctor checks strength, feeling, reflexes, and coordination in arms and legs. Typical findings are weakness and wasting in the distal muscles, reduced sensation in a “glove and stocking” pattern, and reduced reflexes, suggesting a length-dependent peripheral neuropathy.NCBI+1Gait and balance assessment
The clinician watches how the person walks, turns, and stands. They may ask the person to walk on heels or toes or in a straight line. A high-stepping gait, ankle instability, and poor balance are common clues to CMT1.NCBI+1Foot and skeletal inspection
The doctor inspects for high arches, hammertoes, flat feet, or scoliosis. These structural changes help distinguish chronic hereditary neuropathy from some acquired nerve problems.Mayo Clinic+1Reflex testing
Using a reflex hammer, the clinician checks knee and ankle jerks. In CMT1, ankle reflexes are often absent early, and knee reflexes may be reduced later, supporting a peripheral neuropathy diagnosis.NCBI+1Family history and pedigree drawing
The doctor asks about relatives with similar symptoms and may draw a family tree over at least three generations. A pattern where affected individuals appear in every generation and both sexes are affected suggests autosomal dominant inheritance.www.elsevier.com+1
Manual and bedside tests
Manual muscle testing (MRC scale)
The clinician tests each important muscle group by hand and grades strength on a standard scale. Distal muscles (feet, ankles, hands) usually score lower than proximal muscles, consistent with CMT1.NCBI+1Grip strength testing
Hand dynamometers or simple squeeze tests are used to measure how strong the hand is. Reduced grip strength over time helps monitor disease progression and daily function.ClinicalTrials.gov+1Vibration sense testing with tuning fork
A vibrating tuning fork is placed on the big toe or ankle. People with CMT1 often feel the vibration weakly or not at all because large sensory fibers are damaged.NCBI+1Light touch and pin-prick testing
Using cotton or a small pin, the doctor lightly touches the skin and asks what the patient feels. Reduced or absent feeling in the feet and hands supports sensory nerve involvement.NCBI+1Timed walking or functional tests
Simple timed tests, such as a 10-meter walk or 6-minute walk, help measure how quickly and safely a person can move. These tests are useful to follow changes in mobility over time or in clinical trials.ClinicalTrials.gov+1
Lab and pathological tests
Routine blood tests to exclude other causes
Blood tests for blood sugar, vitamin B12, thyroid hormones, kidney and liver function, and sometimes autoimmune markers are done to rule out other treatable causes of neuropathy that can look similar to CMT but are not inherited.NCBI+1Targeted PMP22 duplication / deletion testing
Because CMT1A is the most common type, specific tests that look for duplication (extra copy) or deletion of the PMP22 region on chromosome 17 are often done first. A positive result confirms CMT1A or related PMP22 disorder.Genetic Diseases Center+2CMT Research Foundation+2CMT multigene panel testing
If PMP22 testing is negative, many centers use a next-generation sequencing panel that checks many CMT-related genes at once (such as MPZ, LITAF, EGR2, NEFL). This helps find the exact autosomal dominant demyelinating subtype.KoreaMed Synapse+2Blue Cross NC+2Single-gene sequencing for suspected subtypes
In families with a known mutation, the lab may sequence that single gene (for example, MPZ) in relatives. This confirms who carries the mutation and can guide genetic counseling.KoreaMed Synapse+1Peripheral nerve biopsy (usually sural nerve)
In rare, unclear cases where genetic tests are negative or the presentation is unusual, a small piece of a sensory nerve (often the sural nerve at the ankle) is taken and examined under a microscope. In CMT1, classic changes include “onion bulb” formations showing repeated demyelination and remyelination.PMC+1
Electrodiagnostic tests
Nerve conduction studies (NCS)
Sticky electrodes are placed on the skin over nerves, and small electrical impulses are given. In autosomal dominant demyelinating CMT1, conduction velocities are markedly slowed (often below 35 m/s), which clearly points to a demyelinating neuropathy.NCBI+2PMC+2Electromyography (EMG)
A thin needle electrode is put into different muscles to record activity. EMG can show signs of chronic denervation and reinnervation (long-standing nerve damage), helping to distinguish CMT from muscle diseases.NCBI+1Late responses (F-waves and H-reflexes)
Special parts of nerve conduction testing, such as F-waves and H-reflexes, look at signals traveling back and forth along the nerve. In CMT1 these responses are often delayed or absent, further supporting diffuse peripheral nerve involvement.NCBI+1
Imaging tests
Musculoskeletal MRI of lower legs and feet
MRI images can show patterns of muscle wasting and fatty replacement in the lower legs and feet. These patterns can support the diagnosis and may help distinguish hereditary neuropathy from other neuromuscular diseases.NCBI+1Nerve or plexus MRI / ultrasound
In some centers, MRI or ultrasound of peripheral nerves can show nerve enlargement or abnormal appearance in hereditary neuropathies. While not required for diagnosis, these imaging tests can provide extra structural information in complex cases.NCBI+1
Non-pharmacological treatments
1. Individualized physical therapy program
Physical therapy is one of the most important treatments for CMT1. A trained therapist designs gentle strengthening and stretching exercises that match your weakness, balance and fatigue level. The main goal is to keep muscles working as well as possible without over-tiring them. This usually includes exercises for ankle, knee and hip control, plus core stability to support walking. Regular, moderate exercise can slow functional decline and help prevent contractures (stiff, fixed joints). Physiopedia+2PMC+2
2. Gait and balance training
Many people with demyelinating CMT have foot drop and poor balance, which raise the risk of falls. Physical therapists use targeted gait drills, balance boards, stepping tasks and walking practice on different surfaces. The purpose is to improve how safely and efficiently you walk. The mechanism is repeated practice that retrains the brain and remaining healthy nerves to control muscles better and to use visual and inner-ear signals for balance. PMC+1
3. Ankle-foot orthoses (AFOs)
Light plastic or carbon braces around the ankle and foot can lift the front of the foot, prevent tripping and support weak muscles. They also help control high arches or unstable ankles. The purpose is to stabilize the foot during walking so energy use is lower and walking is safer. Mechanistically, AFOs hold the ankle in a neutral position and change the way forces travel through the foot and leg, which can reduce joint stress. NINDS+2Cleveland Clinic+2
4. Special footwear and insoles
Custom shoes, high-top shoes, or orthotic insoles can support high arches, wide feet or claw toes. The aim is to distribute pressure evenly, protect areas with low sensation and improve balance. Well-designed shoes and inserts work by increasing the contact area under the foot, giving more stability and reducing focal pressure that can cause calluses or ulcers. Cleveland Clinic+1
5. Occupational therapy (hand and daily-living training)
Occupational therapists focus on the hands, arms and everyday tasks such as writing, buttoning clothes, cooking and using a computer. They may teach joint-protection techniques and energy-saving strategies and suggest adaptive tools like built-up pens, zipper pulls or modified kitchen utensils. The purpose is to keep independence in daily life. Mechanistically, they reduce strain on weak muscles and teach alternative ways to perform tasks. NINDS+1
6. Assistive devices for mobility
Canes, trekking poles, walkers, or wheelchairs are sometimes needed. Using these tools is not a failure; they are safety devices. They allow longer walking distances with less fatigue and fewer falls. Mechanistically, they widen your base of support, share the load with the arms and reduce the moment of force at weak ankles and knees. Cleveland Clinic+1
7. Stretching and contracture prevention
Calf, hamstring and hip-flexor tightness is common because of abnormal walking and long-term weakness. Daily stretching routines keep joints moving through their full range and help prevent fixed deformities that later require surgery. Stretching gently lengthens muscles and tendons and preserves joint capsule mobility, making walking and brace use easier. Dove Medical Press+1
8. Strength training of less-affected muscles
Some muscles remain relatively strong in CMT1. Carefully supervised strengthening of these muscles can improve function without damaging weak fibers. Low-resistance, higher-repetition training is usually recommended. The purpose is to “back up” weak muscles by increasing the capacity of still-healthy ones. The mechanism is normal muscle adaptation: more muscle fibers recruited and improved neuromuscular control. PMC+1
9. Aquatic (water-based) therapy
Exercising in warm water supports body weight and reduces the risk of falls. People can practice walking, balance and gentle strengthening with much less stress on joints and feet. The purpose is safe conditioning and improved confidence. The mechanism is buoyancy and water resistance, which provide gentle support while still challenging muscles. PMC+1
10. Respiratory and sleep evaluation
Some CMT types can affect breathing muscles or cause sleep apnea. Sleep studies, breathing tests and non-invasive ventilation at night may be needed. The purpose is to improve oxygen levels, sleep quality and daytime energy. Assisted ventilation works by supporting weak respiratory muscles so they do not have to work as hard during sleep. Dove Medical Press+1
11. Foot care and podiatry
Because sensation in the feet may be reduced, small injuries can go unnoticed and become ulcers or infections. Regular podiatry visits, nail care, corn and callus management, and daily self-inspection of the feet are important. The goal is to prevent ulcers and serious infections. This works like diabetes foot care: early detection of problems before they become severe. NINDS+1
12. Pain psychology and cognitive-behavioural therapy (CBT)
Chronic pain and fatigue can affect mood, sleep and coping. CBT and other psychological therapies help people understand pain, reduce fear and worry, and learn coping skills such as pacing, relaxation and problem-solving. The purpose is not to say pain is “in your head” but to use the brain’s power to reduce suffering. These methods change how pain signals are processed and can reduce the emotional impact of pain. PMC+1
13. Energy-management and fatigue strategies
Fatigue is common in CMT. Therapists teach “pacing”: planning rest breaks, spreading heavy tasks through the week and using equipment (like shower chairs) to reduce effort. The goal is to finish important tasks without over-exhaustion. Mechanistically, this reduces repeated overuse of weak muscles and helps prevent flare-ups of pain and fatigue. PMC+1
14. Workplace and school adaptations
For students and workers, simple changes such as ergonomic chairs, voice-to-text software, alternate duties, or extra time between classes can be key. The purpose is to keep education and work possible and comfortable. These changes reduce long walking distances, heavy lifting and fine-motor strain that may otherwise cause pain or injury. NINDS+1
15. Fall-prevention training and home modifications
Therapists may suggest grab bars in bathrooms, non-slip mats, better lighting, and removing loose rugs or clutter. They may also practise floor-to-stand techniques. The aim is to reduce fractures and head injuries. The mechanism is simple: fewer hazards and better strategies mean fewer falls. Cleveland Clinic+1
16. Weight-management and nutrition counselling
Extra body weight puts more stress on already weak muscles and unstable joints. Dietitians help design balanced, realistic meal plans, often similar to a Mediterranean-style diet rich in fruits, vegetables, whole grains, lean protein and healthy fats. This reduces strain on legs and may support nerve health. Charcot-Marie-Tooth Association+2European CMT Federation+2
17. Anti-inflammatory lifestyle (sleep, stress, smoking)
Good sleep, quitting smoking and managing stress may not change the genes, but they can support overall nerve and muscle health. Chronic stress hormones and tobacco toxins can damage blood vessels and nerves. Reducing them may improve energy and protect remaining nerve function. ScienceDirect+1
18. Genetic counselling for family planning
Because this form of CMT is autosomal dominant, each child often has a 50% chance of inheriting the variant gene. Genetic counsellors explain this risk in simple language and discuss options like prenatal or pre-implantation testing. The purpose is informed family decisions, not to tell people what to do. Dove Medical Press+1
19. Patient support groups and education programs
Connecting with CMT organizations and support groups offers emotional support and practical tips. Education about the condition helps people notice early signs of complications and ask for timely care. The mechanism is shared knowledge and social support, which are known to improve coping in chronic disease. Charcot-Marie-Tooth Association+2Charcot-Marie-Tooth Association+2
20. Regular, long-term follow-up with a neuromuscular clinic
CMT1 usually changes slowly over many years. Regular check-ups with a neurologist and rehabilitation team allow braces, exercises and medicines to be adjusted as needs change. Early intervention when new problems appear can prevent permanent disability. NINDS+2Dove Medical Press+2
Drug treatments
Very important: No medicine currently cures autosomal dominant demyelinating CMT or clearly slows its progression. Most drugs are used to treat symptoms such as neuropathic pain, cramps, mood problems or sleep issues. Many are FDA-approved for neuropathic pain or depression in general, not specifically for CMT, so use is often “off-label” and must be supervised by a doctor. Never start, stop or change any medicine on your own. MDPI+3PMC+3Charcot-Marie-Tooth Association+3
Below, dosage comments are simplified summaries from FDA labels or major references; your own dose may be quite different and should always follow your neurologist’s advice. NCBI+4FDA Access Data+4FDA Access Data+4
1. Pregabalin (Lyrica)
Pregabalin is a gabapentinoid used for neuropathic pain and certain seizures. It binds to calcium channels on nerve cells and reduces the release of pain-related chemicals. FDA labeling for neuropathic pain often starts at about 150 mg per day in divided doses and may be slowly increased if needed, with dose changes guided by kidney function and side effects such as dizziness, sleepiness and weight gain. NCBI+2FDA Access Data+2
2. Gabapentin (Neurontin)
Gabapentin is another gabapentinoid that calms over-active pain pathways. It is widely used for post-herpetic neuralgia and other neuropathic pains and is sometimes used in CMT-related pain. Typical adult regimens for neuropathic pain start around 900 mg/day in three doses and may be increased stepwise, but some people need less and some more. Common side effects include dizziness, sleepiness and swelling of the legs. Charcot-Marie-Tooth Association+3FDA Access Data+3FDA Access Data+3
3. Duloxetine (Cymbalta)
Duloxetine is a serotonin-noradrenaline reuptake inhibitor (SNRI). It is FDA-approved for several chronic pain conditions and depression. It can help neuropathic pain and low mood that sometimes occur with CMT. Many adults are started at 30–60 mg once daily, adjusted slowly as needed. It works by increasing certain brain chemicals that reduce pain signals and improve mood. Nausea, dry mouth and sleepiness are frequent early side effects. FDA Access Data+2FDA Access Data+2
4. Venlafaxine (Effexor and generics)
Venlafaxine is another SNRI sometimes used off-label for neuropathic pain. It boosts serotonin and noradrenaline, which can dampen pain pathways and improve mood and anxiety. Doses usually start low (for example 37.5–75 mg/day in adults) and may be gradually increased. Side effects can include nausea, increased blood pressure, sweating and sleep changes, so monitoring is important. Charcot-Marie-Tooth Association+1
5. Amitriptyline
Amitriptyline is a tricyclic antidepressant (TCA) with a long history of use in nerve pain. Very low doses at night (for example 10–25 mg in adults) are often tried first. It reduces pain by changing how pain signals are processed in the brain and spinal cord and also helps some people sleep. Dry mouth, constipation, blurred vision and morning grogginess are common side effects, and higher doses must be used carefully in heart disease. Charcot-Marie-Tooth Association+1
6. Nortriptyline
Nortriptyline is a related TCA that may cause slightly fewer sedating or anticholinergic effects in some people than amitriptyline. It is also used at low nightly doses for neuropathic pain. Its mechanism is similar: it blocks reuptake of serotonin and noradrenaline to reduce pain signaling. Side effects can include dry mouth, constipation and changes in heart rhythm, so regular review is important. Charcot-Marie-Tooth Association+1
7. Carbamazepine
Carbamazepine is an anticonvulsant that blocks sodium channels in nerves. It is best known for trigeminal neuralgia but can be used for certain shooting nerve pains and cramps. Doses are highly individualized and increased very slowly. It can cause dizziness, low sodium, allergic rashes and blood-count changes, so blood tests and careful monitoring are necessary. Charcot-Marie-Tooth Association+1
8. Oxcarbazepine
Oxcarbazepine is similar to carbamazepine and is sometimes used when nervous-system pain or paroxysmal symptoms are present. It also blocks sodium channels and stabilizes nerve firing. Doses are titrated gradually based on response. Side effects include dizziness, tiredness and hyponatremia (low sodium), so blood monitoring is again important. Charcot-Marie-Tooth Association+1
9. Lamotrigine
Lamotrigine is another anticonvulsant that modulates sodium channels and glutamate release. It can help some neuropathic pain conditions. It must be started at very low doses and increased slowly to lower the risk of serious skin rashes. Dizziness, headache and skin rash are key side effects to watch for. Charcot-Marie-Tooth Association+1
10. Topical lidocaine patches
Lidocaine 5% patches are applied directly to painful skin areas (for example, on the feet) to numb the superficial nerves. They are FDA-approved for post-herpetic neuralgia, and pain specialists sometimes use them for focal neuropathic pain in CMT. The patch is usually worn for up to 12 hours per day. Local skin irritation is the most common side effect. nhs.uk+1
11. Topical capsaicin (low- or high-strength)
Capsaicin creams or patches reduce pain by exhausting certain pain-sensing nerve endings. Low-strength creams are used several times daily; high-strength patches are applied under medical supervision. At first, people may feel burning or stinging, but with repeated use, pain often decreases. This approach is useful when pain is patchy and localized. nhs.uk+1
12. NSAIDs (e.g., ibuprofen, naproxen)
Non-steroidal anti-inflammatory drugs (NSAIDs) do not fix nerve damage but can help muscle and joint pain caused by altered walking mechanics. Many guidelines suggest NSAIDs such as ibuprofen as first-line treatment for musculoskeletal pain in CMT. They work by blocking COX enzymes that make inflammatory prostaglandins. Long-term use can irritate the stomach or affect kidneys and should be monitored. nhs.uk+1
13. Acetaminophen (paracetamol)
Acetaminophen is often used for mild to moderate musculoskeletal pain and has fewer stomach side effects than NSAIDs. It works mainly in the central nervous system to reduce pain and fever. It does not help neuropathic pain very much but can be combined with other treatments. Doses must stay within safe daily limits to avoid liver damage. nhs.uk+1
14. Tramadol (with caution)
Tramadol is a weak opioid that also affects serotonin and noradrenaline. It may be used short-term for severe neuropathic or musculoskeletal pain not controlled by other drugs. Because it can cause dependence, nausea, dizziness and, rarely, seizures or serotonin syndrome (especially when combined with antidepressants), specialists usually keep doses low and for limited times only. nhs.uk+1
15. Baclofen
Baclofen is a muscle-relaxant that acts on GABA receptors in the spinal cord and can help painful muscle spasms or stiffness in some patients. It is usually taken several times a day, starting at low doses. Side effects include drowsiness and weakness, so it must be introduced slowly and not stopped suddenly. PMC+1
16. Tizanidine
Tizanidine is another antispastic medicine that reduces muscle tone by acting on alpha-2 receptors. It may help cramps or stiffness. Blood pressure and liver tests must be monitored because it can cause low blood pressure and liver enzyme changes, as well as drowsiness and dry mouth. PMC+1
17. Low-dose benzodiazepines (e.g., clonazepam – specialist use)
Clonazepam enhances GABA activity and can sometimes help severe night-time cramps or myoclonus. Because benzodiazepines can cause dependence, daytime sleepiness and falls, they are generally reserved for short periods or very specific problems and should be prescribed only by experienced clinicians. PMC+1
18. Antidepressants for mood and anxiety (SSRIs and SNRIs)
Living with a chronic inherited disease can cause anxiety and depression. Standard antidepressants such as SSRIs (for example sertraline) or SNRIs (duloxetine, venlafaxine) can improve mood, sleep and coping, which indirectly improves pain control and daily functioning. Doses and drug choice depend on age, other medicines and side-effect profile. PMC+2FDA Access Data+2
19. Sleep aids (short-term, if needed)
Insomnia worsens pain and fatigue. Non-drug sleep strategies come first, but sometimes short courses of sleep medicines are used. Doctors choose options that avoid worsening muscle weakness or falls, especially in people with balance problems. Mayo Clinic+1
20. Drugs to avoid or use with great caution
Some chemotherapy agents and other “neurotoxic” drugs can worsen CMT neuropathy. Lists from specialist groups highlight medicines such as certain vinca alkaloids and high-dose metronidazole. The purpose of these lists is prevention: your doctors must always know you have CMT before prescribing new medicines. Charcot-Marie-Tooth Disease+1
Dietary molecular supplements
No vitamin or supplement has been clearly proven to cure autosomal dominant demyelinating CMT. Some nutrients are being studied as “adjunct” (extra) therapies to support nerve health or general wellbeing. Always discuss supplements with your doctor, especially if you already take medicines. ScienceDirect+2ontariohealth.org+2
1. Omega-3 fatty acids (fish oil)
Omega-3 fatty acids from fish oil or algae support heart and nerve health and may have anti-inflammatory effects. In neuropathy research, they may help protect nerve membranes. Typical general-health doses are in the range of a few hundred to about 1000 mg of EPA+DHA daily, but exact dosing should follow product labeling and medical advice. Mechanistically, omega-3s become part of nerve cell membranes and can reduce inflammatory signaling. ScienceDirect+1
2. Vitamin D
Vitamin D is important for bones, immunity and muscle function. Low vitamin D is common in many chronic conditions. Supplement doses depend on blood levels; doctors often use daily or weekly vitamin D to reach a safe range. Adequate vitamin D may support muscle strength and reduce fall risk, indirectly helping mobility in CMT. ScienceDirect+1
3. B-complex vitamins (especially B1, B6, B12)
B vitamins take part in energy production and nerve function. Severe deficiencies of B1, B6 or B12 can themselves cause neuropathy. In CMT, correcting any deficiency is important even though it does not fix the genetic cause. Doses vary by vitamin and deficiency level. The mechanism is support of myelin production and nerve energy metabolism. ScienceDirect+1
4. Vitamin E
Vitamin E is a fat-soluble antioxidant. A small early trial in CMT1 studied essential fatty acids combined with vitamin E and suggested some benefit, possibly from membrane stabilization, although evidence is limited. Usual doses must be kept within safe limits because very high doses can increase bleeding risk. PubMed+1
5. Alpha-lipoic acid
Alpha-lipoic acid is an antioxidant used in some countries for diabetic neuropathy. It may improve oxidative stress and blood flow in nerves. For general neuropathic support, doses like 300–600 mg/day have been studied, but its role in CMT is not well proven. It can sometimes lower blood sugar, so monitoring is needed. ScienceDirect+1
6. Acetyl-L-carnitine
Carnitine helps move fatty acids into mitochondria for energy production. Supplements have been studied in some nerve and muscle diseases. In theory, better mitochondrial function could support tired muscles and nerves. Doses vary (often in the range of 500–1000 mg once or twice daily in studies), and gastrointestinal side effects can occur. ScienceDirect+1
7. Magnesium (for cramps)
Magnesium plays a role in muscle relaxation and nerve function. Some people with night cramps feel better when magnesium deficiency is corrected. Typical supplement doses are modest and must consider kidney function. The mechanism is improved muscle membrane stability and reduced excitability. ScienceDirect+1
8. Coenzyme Q10 (CoQ10)
CoQ10 is involved in mitochondrial energy production and acts as an antioxidant. Some neuropathy and muscle studies explore CoQ10 for fatigue and muscle pain. Doses usually range from 100–300 mg/day. It may support energy in nerve and muscle cells, though evidence in CMT specifically is still emerging. ScienceDirect+1
9. Essential fatty acids (linoleic and gamma-linolenic acid)
A classic small trial in CMT1 gave essential fatty acids together with vitamin E for a year. Serum fatty acid levels increased, and some neuropsychological and neurological improvements were maintained, suggesting possible membrane benefits, although the study was small and older. Doses and exact products should be chosen with a clinician. PubMed+1
10. General multivitamin
For many people, a simple multivitamin at recommended daily allowance levels is enough to prevent deficiencies. It supports overall health, immune function and energy. It does not replace a healthy diet but can be a useful safety net when appetite or diet quality is low. ScienceDirect+1
Immunity-booster, regenerative and stem-cell-related drugs
There are no approved stem-cell or gene-editing drugs yet for autosomal dominant demyelinating CMT. Several research directions are being explored; these are experimental and available only in clinical trials or specialist centers. PMC+4MDPI+4MDPI+4
PXT3003 – an oral combination of baclofen, naltrexone and sorbitol studied in CMT1A. Trials suggest potential benefit on disability scores, but it is not yet a widely approved drug. It may work by reducing over-expression of PMP22 and protecting myelin. ResearchGate+1
ACE-083 – a locally injected recombinant protein designed to increase muscle size and strength by blocking myostatin-related pathways. A phase 2 trial in CMT did not meet its main functional endpoint, and development was stopped, but it showed how muscle-targeted therapies might work. PMC+1
Gene-silencing therapies for PMP22 – laboratory and early animal studies have tested small interfering RNAs, antisense oligonucleotides and other tools to lower PMP22 levels in CMT1A. These approaches aim to correct the basic molecular problem and regenerate healthier myelin but are still in research. MDPI+2NMD Journal+2
Gene-replacement or editing approaches – for some axonal CMT types, viral vectors carrying a healthy gene or CRISPR-based editing are being explored. For demyelinating CMT1, similar concepts are under study but not yet in routine clinical use. These are complex therapies done only in specialist centers and clinical trials. NMD Journal+1
Stem-cell-based therapies – experimental work is exploring Schwann cell or mesenchymal stem-cell treatments that might repair myelin or support nerve regeneration. So far, evidence is mostly from animal models or early-phase trials, and no stem-cell product is approved specifically for CMT. NMD Journal+1
Immune-modulating drugs (in selected overlap cases) – CMT itself is not an autoimmune disease, so strong “immunity boosters” do not treat the genetic problem. In rare patients with both CMT and an autoimmune neuropathy, doctors may use standard immune treatments such as IVIG or steroids, but this is very specialized and not routine for pure autosomal dominant demyelinating CMT. PMC+1
Surgeries
1. Foot deformity correction (cavus foot surgery)
Many people with CMT1 develop high-arched (cavus) feet and clawed toes that make walking painful and unstable. Surgeons can perform procedures to lower the arch, straighten toes and balance the pull of different muscles. The aim is a more plantigrade (flat) foot that fits into shoes and braces better, improving walking and reducing pain. Cleveland Clinic+1
2. Tendon transfer surgery
In tendon transfer, a stronger muscle’s tendon is moved to replace the function of a very weak muscle, often around the ankle. For example, a tendon that lifts the foot may be repositioned to correct foot drop. The purpose is to restore more balanced muscle forces so the foot is held in a more normal position during walking. ScienceDirect+1
3. Osteotomy (bone-cutting procedures)
In significant deformity, surgeons may cut and realign bones in the foot or ankle to correct shape. Plates, screws or pins hold the bones while they heal in the new position. The goal is a stable, pain-reduced foot that distributes weight better and reduces calluses and ulcers. ScienceDirect+1
4. Joint fusion (arthrodesis)
When joints are very unstable or painful, fusion surgery can permanently join bones so the joint no longer moves. This can be done in parts of the foot or ankle to correct severe deformity. The trade-off is less movement but more stability and less pain. It is usually considered only after other options have been tried. ScienceDirect+1
5. Spine surgery (for scoliosis or severe deformity)
Some people with CMT develop scoliosis or other spinal deformities. In rare severe cases, spinal fusion or other corrective surgery may be needed to prevent progression, relieve pain or protect breathing. This is done by spine specialists and requires careful planning with the neuromuscular team. Dove Medical Press+1
key prevention strategies
You cannot change the genetic cause of autosomal dominant demyelinating CMT, but you can reduce complications and slow loss of function:
Avoid clearly neurotoxic medicines whenever possible (for example, certain chemotherapy drugs), and always remind doctors you have CMT. Charcot-Marie-Tooth Disease+1
Protect your feet with proper shoes, daily inspection and podiatry to prevent ulcers, infections and unhealed wounds. NINDS+1
Maintain a healthy weight to reduce stress on weak muscles and joints and to lower diabetes risk, which can further damage nerves. European CMT Federation+2Charcot-Marie-Tooth News+2
Follow regular physical and occupational therapy to keep joints moving and muscles as strong as safely possible. Physiopedia+2PMC+2
Use braces and assistive devices early rather than waiting for repeated falls or injuries. Cleveland Clinic+1
Practise fall-prevention at home and outdoors by removing tripping hazards, using handrails and paying attention to uneven ground. Cleveland Clinic+1
Stay up to date with vaccines (for example, flu and pneumonia) to reduce serious infections that could lead to long hospital stays and deconditioning. NINDS+1
Avoid smoking and limit alcohol, as both can worsen nerve damage and balance problems. ScienceDirect+1
Manage other health conditions such as diabetes, thyroid disease or vitamin deficiencies that may add extra nerve injury. ScienceDirect+1
Engage with specialist CMT clinics and research updates, so you can hear about new trials and management options early. MDPI+2Springer+2
When to see a doctor
You should have regular planned follow-ups with a neuromuscular specialist, but see a doctor sooner if:
You notice a clear, new or rapid change in walking, balance or hand strength.
You develop new severe pain, burning or electric-shock sensations in the feet or hands that affect sleep or walking.
You see unhealed sores, colour changes or swelling on your feet or ankles.
You fall more often than before or have near-falls that scare you.
You notice breathlessness, disturbed sleep, loud snoring, morning headaches or feeling unrefreshed despite sleep.
You experience low mood, strong anxiety, or thoughts that life is not worth living – these are health emergencies and need prompt help.
These signs may mean a treatable complication, another overlapping condition, or a need to adjust braces, therapy or medicines. Early review can prevent long-term problems. NINDS+2Mayo Clinic+2
What to eat and what to avoid
There is no special “CMT diet”, but nutrition can support nerve, muscle and bone health and help you control weight and energy. Charcot-Marie-Tooth Disease+4Charcot-Marie-Tooth Association+4European CMT Federation+4
Helpful to eat more of:
Colourful fruits and vegetables – provide vitamins, minerals and antioxidants that support general nerve and muscle health.
Lean proteins – such as fish, poultry, beans and lentils to build and repair muscle.
Whole grains – like brown rice, oats and whole-wheat bread for stable energy and better weight control.
Healthy fats – from olive oil, nuts, seeds and oily fish, which may support nerve membranes and reduce inflammation.
Calcium- and vitamin-D-rich foods – such as low-fat dairy or fortified alternatives to support bones and reduce fracture risk.
Better to limit or avoid:
Highly processed foods and sugary drinks – these add calories without nutrients and can worsen weight and fatigue.
Very salty, fried or fast foods – they increase blood pressure and can contribute to swelling and heart strain.
Excess alcohol – can directly damage nerves and make balance problems worse.
Excess caffeine, especially late in the day – can disturb sleep, which is vital for pain and fatigue control.
Extreme “fad” diets without medical advice – very restrictive plans may cause vitamin or mineral deficiencies and are not proven to treat CMT.
Frequently asked questions (FAQs)
1. Can autosomal dominant demyelinating CMT be cured?
No. At the moment there is no cure and no drug fully proven to stop or reverse the disease. However, many people live long lives with good quality by using therapy, braces, surgery when needed and good pain management. NINDS+2PMC+2
2. Does CMT1 shorten life expectancy?
For most people with CMT1, life expectancy is near normal. The main issues are mobility, pain, fatigue and, in some, breathing or spine problems. Good follow-up and management can reduce complications. NINDS+1
3. Is autosomal dominant demyelinating CMT always severe?
No. Even within the same family, severity can vary from very mild (only high arches) to more significant disability requiring braces or wheelchairs. The disease usually progresses slowly over years. Dove Medical Press+1
4. Can exercise make CMT worse?
Very hard or high-impact exercise can over-strain weak muscles, but supervised, moderate exercise is usually helpful. A physical therapist who knows neuromuscular disease can design a safe plan. PMC+2Charcot-Marie-Tooth Association+2
5. Are there special shoes for CMT?
Yes. Many people benefit from custom orthotics, high-top shoes, extra-depth shoes or boots that fit braces. An orthotist or podiatrist can recommend options to improve comfort and balance. Cleveland Clinic+1
6. Are there any promising new drugs?
Several approaches, such as PXT3003, ACE-083 and gene-based therapies, are in research stages, mainly for CMT1A. None are yet widely approved, but clinical trials are ongoing. Springer+3ResearchGate+3PMC+3
7. Should I take vitamin supplements?
Correcting real deficiencies (like low vitamin D or B12) is important, but taking very high doses “just in case” is not proven to help and can be harmful. Ask your doctor to check levels and guide safe doses. ScienceDirect+1
8. Is CMT1 contagious?
No. CMT is purely genetic, passed through families, and cannot be caught from another person. NINDS+1
9. Can children be tested for the family gene?
Genetic testing is possible if the family mutation is known. Whether to test children is a sensitive decision usually discussed with a genetic counsellor, considering emotional and practical issues. Dove Medical Press+1
10. Can pregnancy make CMT worse?
Some women report temporary worsening of symptoms during pregnancy due to weight gain and fluid changes, but long-term progression is usually similar. Obstetric and neuromuscular teams should work together for safe care. Dove Medical Press+1
11. Are braces permanent?
Many people use braces long-term because they make walking safer and less tiring. Some use them only for long distances. Braces can be changed as your needs change. Cleveland Clinic+1
12. Can I still work or study?
Yes. Many people with CMT study and work successfully. You may need adjustments such as ergonomic equipment, flexible schedules or extra time between classes to rest. Early planning helps a lot. NINDS+1
13. What about mental health?
Living with a chronic genetic disease can be emotionally hard. It is completely okay to ask for counselling, support groups or medicines for anxiety or depression. Treating mental health often improves pain and fatigue too. PMC+1
14. Should family members be screened?
Because this form is autosomal dominant, first-degree relatives (parents, children, siblings) may choose clinical or genetic evaluation. This is especially useful if they have subtle symptoms or are planning children. Dove Medical Press+1
15. Where can I learn more and join research?
National neurology institutes and CMT organizations publish plain-language information, list clinical trials and offer webinars. Your neurologist can help you find reliable sites and, if appropriate, refer you to a research center. NINDS+2MDPI+2
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: December 31, 2025.
