Autosomal dominant axonal Charcot-Marie-Tooth disease type 2C (often shortened to CMT2C) is a rare inherited nerve disease. It mainly damages the long “wires” (axons) of the peripheral nerves, which carry signals from the brain and spinal cord to the muscles and back from the skin. This damage causes weakness, wasting of muscles, and reduced feeling, especially in the feet, legs, hands and arms. In CMT2C, nerves that control the voice box (vocal cords), breathing muscles (diaphragm), and sometimes hearing are also affected. Orpha+2National Organization for Rare Disorders+2
“Autosomal dominant” means the disease is caused by a harmful change (mutation) in only one copy of a gene, and that a parent with the mutation has a 50% chance to pass it to each child, whether the child is male or female. NCBI
Autosomal dominant axonal Charcot-Marie-Tooth disease type 2C (CMT2C) is a rare inherited nerve disease. “Autosomal dominant” means a person can get the condition if they receive one changed gene from either parent. “Axonal” means the damage mainly affects the long “wires” of the nerve cells, not the insulation around them. In CMT2C, the TRPV4 gene is usually changed, which upsets how nerve cells handle calcium and other signals. neurology.org+1
CMT2C mainly attacks the peripheral nerves, which control movement and feeling in the feet, legs, hands, and arms. Many people also develop vocal cord weakness, breathing problems from diaphragm weakness, and sometimes hearing loss. This combination of limb weakness, vocal cord paresis, and possible breathing trouble is a key feature of CMT2C. National Organization for Rare Disorders+2Charcot-Marie-Tooth Disease+2
Most people with CMT2C have a mutation in a gene called TRPV4. This gene makes a protein that acts like a small channel in the cell membrane and controls the flow of calcium and other ions. When TRPV4 does not work correctly, the nerve cells become stressed and slowly degenerate, leading to the symptoms of this disease. PMC+2Europe PMC+2
Other Names
Doctors and researchers use several other names for autosomal dominant axonal Charcot-Marie-Tooth disease type 2C. These names all refer to the same or very closely related conditions:
Charcot-Marie-Tooth disease type 2C (CMT2C) Orpha+1
Charcot-Marie-Tooth neuropathy type 2C
Hereditary motor and sensory neuropathy type IIC (HMSN2C) NCBI+2NCBI+2
Charcot-Marie-Tooth disease, axonal, autosomal dominant, type 2C
TRPV4-related Charcot-Marie-Tooth disease type 2C
These different names usually reflect how the disease was first described (by symptoms, by the nerves affected, or by the gene involved).
In simple words, CMT2C is a slowly progressive nerve disease that you are born with because of a gene change. The long nerves to the feet and hands are damaged first, so people often notice tripping, foot drop, or weak grip. In this special type 2C, the nerves to the voice box and breathing muscles can also be involved, so some people develop a hoarse voice, trouble speaking loudly, or shortness of breath when lying flat or during sleep. Orpha+2National Organization for Rare Disorders+2
The disease can start in childhood, teenage years or adulthood. Some people have mild problems and walk almost normally for many years. Others have more severe weakness and may later need walking aids or breathing support at night. The course is usually slowly progressive over many years. Global Genes+2Charcot-Marie-Tooth Disease+2
Types (Clinical Patterns)
Doctors sometimes talk about clinical patterns or “types” inside CMT2C to describe how the disease looks in different people. These are not formally separate diseases, but useful groups: nmd-journal.com+2Springer Link+2
Classical CMT2C pattern – Distal leg and foot weakness and wasting, reduced feeling, plus vocal cord weakness and possible diaphragm weakness.
CMT2C with prominent respiratory involvement – Limb weakness plus early or marked involvement of the diaphragm, causing shortness of breath, weak cough, and sleep-related breathing problems.
CMT2C with hearing problems – Limb neuropathy plus sensorineural hearing loss, leading to difficulty understanding speech, especially in noisy places. Global Genes+1
CMT2C with scapuloperoneal spinal muscular atrophy overlap – Weakness is more obvious in shoulder girdle and peroneal muscles (around the lower leg), with features overlapping scapuloperoneal spinal muscular atrophy due to TRPV4 mutation. Springer Link
Mild or late-onset CMT2C – Symptoms begin in mid- or late adulthood and progress slowly, sometimes with limited vocal cord or respiratory involvement. nmd-journal.com+1
Causes and Risk Factors
Remember: the main true cause is the TRPV4 gene mutation. The other points below are factors that can worsen nerve damage or symptoms, not separate primary causes of CMT2C.
TRPV4 gene mutation (primary cause)
A harmful change (mutation) in the TRPV4 gene is the key cause of CMT2C. This mutation makes the TRPV4 protein over-active or mis-behaving, leading to too much calcium entry into nerve cells, cellular stress, and gradual axonal degeneration. PMC+2Europe PMC+2Autosomal dominant inheritance from a parent
Many patients inherit the mutation from an affected mother or father. Because the pattern is autosomal dominant, each child of an affected parent has about a 50% chance to inherit the mutation and develop the disease. NCBI+1New (de novo) TRPV4 mutation
In some people, the TRPV4 mutation appears for the first time in that person, without any family history. This is called a de novo mutation and happens when the egg or sperm cells are formed. NCBI+1Modifier genes
Other genes may change how severe CMT2C becomes. Some people with the same TRPV4 mutation can have very different levels of weakness and breathing problems. This suggests that “modifier” genes alter nerve resilience and disease expression. nmd-journal.com+1Age-related nerve vulnerability
As people get older, all nerves naturally lose some function. In someone with CMT2C, this normal age-related change can add to the genetic damage and make symptoms appear or worsen in mid- or late life. ScienceDirect+1Repeated mechanical stress on nerves
Frequent ankle sprains, tight shoes, or repeated compression of nerves (for example, crossing legs for a long time) can further injure already fragile axons, increasing weakness or numbness in the feet.Poorly controlled diabetes
Diabetes can cause a separate peripheral neuropathy. If a person with CMT2C also has diabetes, the two nerve problems may add together and cause faster or more severe nerve damage. ScienceDirect+1Vitamin deficiencies (especially B12)
Severe vitamin B12 or folate deficiency can damage nerves and spinal cord. In a person with CMT2C, this extra insult can worsen balance problems and numbness.Thyroid dysfunction
Both severe hypothyroidism and hyperthyroidism can affect nerve and muscle function. If thyroid problems are not treated, they may increase fatigue, weakness, and cramps in people with CMT2C.Alcohol misuse
Heavy, long-term alcohol use can cause toxic peripheral neuropathy. When present in someone with CMT2C, this can speed up loss of sensation and muscle strength.Neurotoxic medications
Certain chemotherapy drugs (like vincristine) and some other medicines are known to damage peripheral nerves. Doctors usually try to avoid or adjust these drugs in patients with hereditary neuropathies. ScienceDirect+1Chronic kidney disease
Toxins that build up in kidney failure can injure nerves. If CMT2C patients develop kidney disease, they may notice faster progression of tingling, numbness, and weakness.Uncontrolled autoimmune diseases
Autoimmune neuropathies or systemic autoimmune diseases (like lupus) can add inflammatory damage to the nerves and may temporarily or permanently worsen disability.Infections that affect nerves
Infections such as severe influenza, COVID-19, or other viruses can sometimes worsen weakness or breathing problems, especially when respiratory muscles are already weak.Sleep apnea or obesity
Obesity and sleep apnea strain breathing muscles and reduce oxygen levels at night. In CMT2C, where the diaphragm may already be weak, these factors can increase daytime fatigue and shortness of breath. OUP Academic+1Smoking
Smoking reduces blood flow and oxygen to nerves and muscles. Long-term smoking can therefore make numbness and weakness worse in hereditary neuropathies.Sedentary lifestyle
Lack of physical activity leads to muscle deconditioning. Weak muscles around unstable joints (such as ankles and knees) may lose strength faster in CMT2C if they are not used regularly.Inappropriate high-impact exercise
Very intense, high-impact sports or activities that cause repeated ankle and knee injuries can worsen joint deformities and pain in people with weak distal muscles. Moderate, low-impact exercise is usually safer. ScienceDirectPoor foot care
If foot deformities or pressure points are not managed with proper shoes or orthotics, repeated small injuries and ulcers can appear and may limit walking even more.Delayed diagnosis and lack of rehabilitation
When the condition is not recognized early, people may not receive physiotherapy, orthotics, or breathing support in time. This can lead to preventable falls, contractures, and respiratory complications. ScienceDirect+1
Symptoms and Signs
Distal leg and foot weakness
The earliest sign is often weakness in the lower legs and feet. People may have trouble running, climbing stairs, or standing on tiptoe. The front-of-leg muscles that lift the foot are especially weak, causing the toes to drag. Orpha+2monarchinitiative.org+2Foot drop and tripping
Because the foot does not lift properly during walking, the toes can catch on the ground. This “foot drop” makes people trip or stumble easily and may lead to falls.High-arched feet and other foot deformities
Over time, muscle imbalance around the ankle can cause high arches (pes cavus), hammer toes, and a narrow foot. These deformities make shoe fitting difficult and increase pressure points. pfmjournal.org+1Distal hand weakness and poor grip
Many patients later develop weakness in the small muscles of the hands. They may have trouble opening jars, writing for a long time, doing buttons, or fine tasks like sewing. pfmjournal.org+1Muscle wasting (atrophy)
As nerves fail to stimulate the muscles, the muscles become thin. This is especially visible in the calves, feet, and hands, where the legs look “stork-like” and the hands appear bony. ResearchGate+1Numbness and reduced sensation
Loss of feeling in the toes and fingers is common. People may not feel light touch, vibration, or pain normally. This can make it hard to notice small injuries, burns, or blisters on the feet. Orpha+2monarchinitiative.org+2Tingling, burning, or electric shock sensations
Some patients feel unpleasant tingling, pins-and-needles, or burning pain in their feet and sometimes in their hands. These “neuropathic pains” happen because damaged nerves send abnormal signals.Vocal cord weakness and hoarseness
A hallmark of CMT2C is involvement of nerves that control the vocal cords. People may have a hoarse or breathy voice, reduced loudness, voice fatigue, or frequent throat clearing. In severe cases, airway obstruction may occur. Orpha+2Charcot-Marie-Tooth Disease+2Difficulty breathing, especially when lying flat
Weakness of the diaphragm and other breathing muscles can cause shortness of breath when lying down, climbing stairs, or during infections. Some people develop morning headaches, poor sleep, or daytime sleepiness from nocturnal hypoventilation. PMC+2Europe PMC+2Weak cough and frequent chest infections
When breathing muscles are weak, the cough becomes weak and cannot clear mucus well. This increases the risk of chest infections and pneumonia, especially during colds or flu. OUP Academic+1Hearing problems
Some patients have sensorineural hearing loss, especially for high-frequency sounds. They may need people to repeat words, find noisy places difficult, or use hearing aids. Global Genes+1Loss of reflexes
At the ankle and sometimes at the knee, tendon reflexes may be reduced or absent. Doctors often find this during neurological examination, even before symptoms are very obvious. pfmjournal.org+1Balance problems and unsteady gait
Because of muscle weakness and loss of joint position sense, people with CMT2C may have trouble walking on uneven ground, in the dark, or with their eyes closed. They may sway or feel “wobbly”.Fatigue and reduced exercise tolerance
Walking and simple activities cost more effort when muscles are weak and breathing is less efficient. Many patients feel tired easily and need more rest after physical tasks.Emotional and social impact
Chronic weakness, deformity, and breathing problems can cause anxiety, low mood, and social withdrawal. People may feel embarrassed by their voice changes or walking difficulties and need emotional support and counseling.
Diagnostic Tests
Physical Examination
General neurological and musculoskeletal examination
The doctor looks at muscle bulk, strength, reflexes, and sensation in all four limbs. They also check foot shape, spine posture, and joint flexibility. In CMT2C, they usually find distal weakness, muscle wasting, reduced ankle reflexes, sensory loss, and foot deformities, which suggest an axonal peripheral neuropathy. ScienceDirect+2pfmjournal.org+2Gait and functional assessment
The patient is asked to walk normally, on heels and toes, and in a straight line. The doctor observes foot drop, ankle instability, sway, and ability to rise from a chair or climb onto an exam table. Difficulty with heel walking and frequent tripping support the diagnosis of distal motor neuropathy. pfmjournal.orgRespiratory examination
The doctor inspects chest expansion, breathing pattern, and use of accessory muscles. They listen with a stethoscope and may measure simple bedside indicators like counting aloud in one breath. Reduced chest movement, shallow breathing, and weak cough raise suspicion of diaphragm involvement in CMT2C. OUP Academic+1Ear, nose, throat (ENT) and voice assessment
An ENT specialist listens to the patient’s voice and looks for hoarseness, breathiness, or vocal fatigue. Simple tasks such as sustained vowel sounds or speaking loudly help reveal vocal cord weakness. This clinical impression often leads to more detailed laryngeal tests. Orpha+1
Manual Bedside Tests
Manual muscle testing (MRC scale)
The doctor tests each major muscle group by asking the patient to move against resistance. Strength is graded from 0 (no movement) to 5 (normal). In CMT2C, distal muscles (ankle dorsiflexors, toe extensors, small hand muscles) often score lower than proximal muscles, showing a length-dependent axonal neuropathy pattern. pfmjournal.org+1Bedside sensory testing
Using simple tools (cotton, pin, tuning fork), the examiner checks touch, pain, temperature, and vibration in the feet and hands. People with CMT2C often have reduced vibration and pin-prick sensation in a “stocking-and-glove” distribution, supporting involvement of long sensory axons. Orpha+2monarchinitiative.org+2Bedside respiratory measures (such as breath-count test)
The patient is asked to take a deep breath and count out loud as far as possible in one breath. A low count suggests weak breathing muscles. Simple peak cough flow and incentive spirometry can also be done manually in the clinic to screen for diaphragm weakness. OUP Academic+1Bedside voice and swallow tests
The patient sustains vowel sounds, reads a passage, or swallows water under observation. Choking, wet voice, or obvious voice fatigue may point to vocal cord dysfunction, prompting formal laryngoscopy and speech-language assessment. Orpha+2Lippincott Journals+2
Laboratory and Pathological Tests
Routine blood tests to rule out other neuropathies
Doctors usually order tests such as full blood count, blood sugar, kidney and liver function, vitamin B12, folate, and thyroid function. These tests do not diagnose CMT2C directly but help exclude other treatable causes of neuropathy that can mimic or worsen symptoms. ScienceDirect+1Creatine kinase (CK) level
CK is an enzyme released from damaged muscles. In CMT2C, CK may be normal or mildly raised. A very high CK would suggest another muscle disease, so this test helps with differential diagnosis. ScienceDirect+1Genetic testing for TRPV4 mutation
This is the key confirmatory test. A blood sample (or sometimes saliva) is used to sequence the TRPV4 gene or a panel of neuropathy-related genes. Finding a known pathogenic TRPV4 variant in a person with compatible clinical features confirms the diagnosis of TRPV4-related CMT2C. NCBI+2PMC+2Nerve biopsy (rarely needed now)
In older practice, a small piece of a sensory nerve (often the sural nerve) was removed and examined under the microscope. Axonal loss and secondary myelin changes would be seen in CMT2C. Today, with easier access to genetic testing, nerve biopsy is reserved for unclear cases. ScienceDirect+1
Electrodiagnostic Tests
Nerve conduction studies (NCS)
Small electrical impulses are applied to the nerves in the arms and legs, and responses are recorded. In CMT2C, nerve conduction studies usually show reduced amplitudes of sensory and motor responses with relatively preserved conduction velocities, indicating an axonal rather than demyelinating neuropathy. PMC+2ResearchGate+2Electromyography (EMG)
A tiny needle electrode is inserted into different muscles to record electrical activity. EMG in CMT2C typically shows signs of chronic denervation and reinnervation (large motor units, reduced recruitment), confirming ongoing axonal loss and compensatory sprouting. ResearchGate+2nmd-journal.com+2Phrenic nerve conduction and diaphragm EMG
In patients with breathing symptoms, special electrodiagnostic tests can study the phrenic nerve (which drives the diaphragm) and the diaphragm muscle itself. Reduced responses or abnormal EMG patterns support diaphragm involvement and help guide decisions about non-invasive ventilation. OUP Academic+1Laryngeal EMG
For patients with severe voice symptoms, laryngeal EMG examines the electrical activity of muscles that move the vocal cords. Abnormal patterns consistent with neuropathy confirm that vocal cord paresis is due to nerve damage, as seen in CMT2C, rather than a structural lesion like a tumor. Lippincott Journals+1
Imaging Tests
MRI or CT of brain and spine (to exclude other causes)
Brain and spine imaging are often done to rule out other conditions that can mimic neuropathy, such as spinal cord compression, multiple sclerosis, or tumors. In CMT2C, MRI and CT are usually normal or show only non-specific changes, which helps point back to a peripheral neuropathy. ScienceDirect+1Chest X-ray or ultrasound for diaphragm position
Imaging of the chest can show an elevated diaphragm if it is weak or paralyzed. Ultrasound can also measure diaphragm movement during breathing. These tests support a diagnosis of diaphragm involvement in patients with shortness of breath. OUP Academic+1Laryngoscopy (endoscopic view of vocal cords)
A thin flexible camera is passed through the nose or mouth to directly see the vocal cords. In CMT2C, laryngoscopy often shows reduced movement or paralysis of one or both cords during breathing and speech. This finding explains hoarseness and confirms laryngeal nerve involvement. Orpha+2Lippincott Journals+2Muscle and nerve ultrasound
High-resolution ultrasound can show thinning of muscles, increased connective tissue, and sometimes changes in peripheral nerves. Although not specific to CMT2C, it provides a non-invasive way to visualize neuromuscular damage and can support the diagnosis together with other tests. ScienceDirect+1
Non-pharmacological treatments (therapies and other supports)
1. Physiotherapy and stretching
Purpose: Keep muscles strong and flexible, slow contractures, and support safe walking. Mechanism: Gentle resistance exercises and daily stretching help muscles work better and joints move through their full range. In CMT, this may delay stiffness and reduce falls, even if it cannot stop nerve damage. A physiotherapist adjusts the plan to the person’s weakness, fatigue, and balance problems. PMC+2Lippincott Journals+2
2. Occupational therapy (OT)
Purpose: Help with hand use, self-care, school, work, and daily tasks. Mechanism: An occupational therapist teaches ways to save energy, use both hands more safely, and choose tools like built-up pens, button hooks, and adapted keyboards. This reduces strain on weak hand and wrist muscles and can keep people independent longer. Physiopedia+1
3. Balance and gait training
Purpose: Lower the risk of falls and injuries. Mechanism: Special exercises train the body to react better when balance is disturbed. They use standing on different surfaces, stepping tasks, and safe “near-fall” practice. These drills help the brain make the most of remaining nerve signals and improve confidence in walking. PMC+1
4. Low-impact strength training
Purpose: Maintain as much strength as possible in muscles that are not yet badly damaged. Mechanism: Light weights, resistance bands, and body-weight exercises are used at a safe, sub-maximal level. This encourages muscle fibers to stay active without over-tiring fragile nerves. Over-heavy exercise is avoided because it may worsen fatigue and strain. PMC+1
5. Aerobic exercise (walking, cycling, swimming)
Purpose: Improve heart and lung fitness, mood, and overall health. Mechanism: Regular, gentle aerobic activity increases oxygen delivery and blood flow to nerves and muscles. Swimming or stationary cycling are often chosen because they support the body and reduce joint impact, which is helpful in people with weak ankles and feet. PMC+1
6. Ankle-foot orthoses (AFOs) and foot orthotics
Purpose: Control foot drop, stabilize ankles, and reduce tripping. Mechanism: AFOs hold the ankle at a safe angle so the toes do not drag. Custom insoles support high arches or cavovarus feet, spreading pressure more evenly. This improves walking pattern, lowers fall risk, and may delay need for surgery. Pod NMD+2Lippincott Journals+2
7. Hand splints and wrist supports
Purpose: Improve grip and hand function and prevent deformities. Mechanism: Lightweight splints position the wrist and fingers in a more neutral posture, giving hand muscles a better length to work at. This can make activities like writing, typing, and using tools easier and less tiring. PMC+1
8. Respiratory therapy and non-invasive ventilation
Purpose: Support breathing when diaphragm weakness or chest muscle weakness appears. Mechanism: Breathing exercises, cough-assist devices, and night-time non-invasive ventilation (like BiPAP) help clear mucus and keep oxygen and carbon dioxide levels safe. This can reduce morning headaches, daytime sleepiness, and hospital stays. cdn.fortunejournals.com+1
9. Speech and voice therapy
Purpose: Help with hoarse voice, weak voice, and swallowing problems from vocal cord paresis. Mechanism: A speech-language pathologist teaches breathing-voice coordination, safe swallowing postures, and pacing of speech. These strategies let people communicate more clearly and lower the chance of choking, while waiting to see if surgery is needed. PubMed+1
10. Hearing aids and audiologic rehabilitation
Purpose: Manage hearing loss that can occur in some people with CMT2C. Mechanism: Hearing aids amplify sounds, while listening training teaches strategies like lip-reading and noise control. Better hearing reduces social isolation and helps the person follow school or work activities despite nerve damage to the auditory system. Charcot-Marie-Tooth Disease+1
11. Pain psychology and cognitive-behavioural therapy (CBT)
Purpose: Help people cope with chronic pain, fatigue, and emotional stress. Mechanism: CBT and similar therapies teach skills like pacing, relaxation, and reframing negative thoughts. These tools do not remove pain but can reduce suffering, improve sleep, and support long-term mental health in CMT. PMC+1
12. Assistive devices (canes, walkers, wheelchairs, scooters)
Purpose: Keep people mobile and safe when walking becomes difficult. Mechanism: Mobility aids shift some weight from weak muscles to the device. This saves energy, helps prevent falls, and lets people take part in school, work, and social life for longer distances without exhaustion. PMC+1
13. Home and school safety modifications
Purpose: Make daily environments safer and more accessible. Mechanism: Simple changes such as removing loose rugs, adding grab bars, using non-slip mats, and making sure there is good lighting all over the home can cut fall risk. School or workplace changes might include elevator access or extra time to move between rooms. Lippincott Journals+1
14. Custom footwear and shoe adaptations
Purpose: Improve stability and comfort for high-arched or deformed feet. Mechanism: Shoes with firm heel counters, wide toe boxes, rocker soles, or built-in braces help match the foot’s shape. This spreads pressure and supports weak muscles, making walking safer and less painful. PMC+1
15. Hydrotherapy (water-based therapy)
Purpose: Exercise with less stress on joints and weak muscles. Mechanism: Warm water supports body weight and relaxes muscles. Walking or exercising in a pool lets people with CMT2C work on strength and balance in a safer, slower, and more controlled way than on land. PMC+1
16. Gentle yoga or tai chi (with supervision)
Purpose: Improve flexibility, breathing, and body awareness. Mechanism: Slow, controlled movements and breathing exercises help joint mobility and balance. A teacher who understands neuromuscular disease can adapt poses, avoid overstretching, and focus on safe, supported postures. PMC+1
17. Nutritional counselling
Purpose: Maintain a healthy body weight and good overall nutrition. Mechanism: A dietitian helps plan meals rich in vitamins, minerals, and protein while avoiding under-nutrition or obesity. This supports muscle health, immune function, and wound healing, and may lower the risk of diabetes and other problems that can worsen neuropathy. PMC+1
18. Genetic counselling
Purpose: Give information about inheritance, family planning, and testing. Mechanism: A genetic counsellor explains how autosomal dominant CMT2C is passed down, the chance of having affected children, and options such as carrier testing or prenatal / pre-implantation genetic diagnosis. This helps families make informed, personal choices. National Organization for Rare Disorders+1
19. Patient support groups and peer networks
Purpose: Provide emotional support and practical tips. Mechanism: Meeting others with CMT2C or other CMT types, in person or online, helps people feel less alone. They can share experience about braces, therapies, school and work issues, and research updates in an understandable way. cmt.org.au+1
20. Mental health care (counselling, psychiatry)
Purpose: Treat depression, anxiety, or stress that often come with chronic illness. Mechanism: Psychologists and psychiatrists can use talk therapy and, when needed, medicines to stabilize mood and anxiety. Good mental health makes it easier to follow exercise plans, use braces, and participate in social life. PMC+1
Drug treatments
Important: There is no medicine currently approved by the FDA specifically for CMT2C. Drugs are used to treat symptoms like nerve pain, cramps, anxiety, or sleep problems. Doses must always be set by a doctor for each person. PMC+2PMC+2
I will briefly describe 20 medicine types often used in peripheral neuropathy care. These are examples only, not treatment advice.
1. Gabapentin (neuropathic pain modulator)
Gabapentin is an anti-seizure drug also used for nerve pain. It calms overactive nerve cells by affecting calcium channels in the brain and spinal cord. Doctors usually start at a low dose and slowly increase, often divided through the day. Purpose is to reduce burning, shooting, or tingling pain. Common side effects include sleepiness, dizziness, and weight gain. PMC
2. Pregabalin
Pregabalin is similar to gabapentin but is absorbed more predictably. It also binds to calcium-channel subunits in nerve cells, reducing release of pain-signalling chemicals. It is usually taken two or three times a day. It can ease neuropathic pain and improve sleep, but may cause dizziness, swelling of legs, and weight gain. PMC+1
3. Duloxetine (SNRI antidepressant)
Duloxetine is an antidepressant and anti-anxiety drug that is also licensed for some nerve pains. It increases serotonin and noradrenaline in the brain and spinal cord, helping the body’s own pain-control systems. It is usually taken once daily. It may help pain and mood together, but can cause nausea, dry mouth, and increased sweating. PMC
4. Amitriptyline (tricyclic antidepressant)
Amitriptyline is an older antidepressant often used at low doses at night for neuropathic pain. It blocks reuptake of serotonin and noradrenaline and has calming effects. It can improve sleep and reduce pain signals. Side effects include dry mouth, constipation, and morning grogginess, so doctors titrate dose very carefully. PMC+1
5. Nortriptyline
Nortriptyline is similar to amitriptyline but sometimes better tolerated. It also boosts serotonin and noradrenaline in pain-control pathways. It is usually taken in the evening. It may cause less sedation and fewer heart-related side effects than amitriptyline, but still needs careful medical supervision and sometimes ECG checks. PMC
6. Topical lidocaine (patches or creams)
Lidocaine patches or gels numb painful skin areas. They block sodium channels in small nerve fibers, so pain signals cannot travel as easily. They are applied over painful zones for set hours each day. Side effects are usually mild skin irritation. Because they work mostly locally, they may be safer than systemic drugs for some people. PMC+1
7. Acetaminophen (paracetamol)
Acetaminophen is a simple pain reliever for mild pain or fever. It works mainly in the central nervous system to lower pain signals. It does not treat nerve damage itself, but may add to other pain medicines. It must be kept below a safe daily limit to avoid liver damage, especially if combined with other acetaminophen-containing products. PMC+1
8. Non-steroidal anti-inflammatory drugs (NSAIDs)
NSAIDs such as ibuprofen or naproxen reduce inflammation and help joint or muscle pain. They block COX enzymes and lower prostaglandin production. In CMT2C they can help with secondary joint pain from abnormal walking. Long-term use can irritate the stomach and affect kidneys or blood pressure, so doctors choose dose and duration carefully. PMC+1
9. Baclofen (muscle relaxant)
Baclofen acts on GABA-B receptors in the spinal cord to reduce muscle spasticity and cramps. In CMT it may help painful cramps or stiffness in legs. A combination of baclofen, naltrexone, and sorbitol was given orphan-drug designation for CMT1A, showing interest in this pathway, but it is not yet approved for any CMT type. FDA Access Data+2Charcot-Marie-Tooth Disease+2
10. Tizanidine
Tizanidine is another muscle relaxant that acts on alpha-2 receptors. It can reduce spasticity and sometimes cramps. It is usually taken in small divided doses. Side effects include low blood pressure, sleepiness, and dry mouth, so doctors monitor closely and may check liver tests. PMC+1
11. Tramadol (weak opioid-like analgesic)
Tramadol is used for moderate pain when other drugs are not enough. It works both as a weak opioid and as a serotonin–noradrenaline reuptake inhibitor. Because it can cause dependence, drowsiness, and seizures, it must be used cautiously, for the shortest time possible, and always under strict medical supervision. PMC+1
12. Selective serotonin reuptake inhibitors (SSRIs, e.g., sertraline)
SSRIs are not pain medicines but treat depression and anxiety, which are common in chronic disability. By improving mood and reducing anxiety, they can indirectly reduce the feeling of pain and improve coping skills. Doses are started low and increased slowly to limit nausea, headaches, and sleep changes. PMC+1
13. Benzodiazepines (short-term for severe anxiety or spasms)
Short courses of benzodiazepines may be used for severe anxiety or sleep disruption in selected adults. They enhance GABA action and calm the nervous system. However, they can cause dependence, falls, and memory problems, so they are usually avoided long term and are not first-line drugs in young people. PMC+1
14. Melatonin (sleep aid; often considered a supplement)
Melatonin helps regulate sleep–wake cycles. In people with CMT who struggle with pain, breathing issues, or anxiety at night, low-dose melatonin may improve sleep quality. It works on melatonin receptors in the brain to signal “night-time.” Dosing and timing differ by age and must be decided with a doctor. PMC
15. Short-acting bronchodilators (if breathing symptoms overlap)
Some people with diaphragm weakness may also have airway tightness or asthma-like symptoms. In those cases, inhalers that open airways can be used. They relax muscles around the small airways. They do not treat nerve damage but can make breathing easier during infections or exertion. cdn.fortunejournals.com+1
16. Long-term oxygen therapy (in selected advanced cases)
Oxygen is not a “drug” in the usual sense, but it is a prescribed therapy. If chronic respiratory failure develops, oxygen may be given, often with ventilatory support. It raises oxygen levels in the blood but needs careful monitoring to avoid making CO₂ retention worse. cdn.fortunejournals.com+1
17. Antibiotics (for chest infections)
People with weak breathing muscles may get lung infections more easily. When a bacterial infection is suspected, antibiotics are used to clear it and protect lung function. The exact drug depends on local resistance patterns and allergy history. Good chest care plus timely antibiotics can prevent serious complications. cdn.fortunejournals.com+1
18. Proton-pump inhibitors (PPIs) for reflux
Acid reflux is common in chronic illness, especially if people lie down more or use certain medicines. PPIs reduce acid production in the stomach. This can protect the oesophagus and reduce the risk of aspiration, which is more dangerous when breathing muscles are weak. cdn.fortunejournals.com+1
19. Experimental muscle-targeted drug NMD670 (research only)
NMD670 is a small-molecule drug in clinical trials that targets the skeletal-muscle chloride channel ClC-1, aiming to improve muscle response to weak nerve signals. The FDA has granted it orphan-drug designation for CMT, but it is not yet an approved treatment and should only be used in clinical studies. NMD Pharma+2Charcot-Marie-Tooth Disease+2
20. Other investigational agents (e.g., PXT3003, EN001, govorestat – research only)
Several investigational therapies are being studied in other types of CMT, not CMT2C specifically. These include PXT3003 for CMT1A, govorestat for CMT-SORD, and EN001, which recently received orphan-drug designation. Some trials have had mixed or negative results, so these drugs are not standard care yet. CMT Research Foundation+4ClinicalTrials.gov+4PMC+4
Dietary molecular supplements
Note: No supplement has been proven to cure or halt CMT2C. Evidence is limited, and supplements can interact with medicines. Always discuss them with a doctor. PMC+1
I will list 10 commonly discussed supplements in neuropathy care.
1. Alpha-lipoic acid
Alpha-lipoic acid is an antioxidant used in some diabetic neuropathy studies. It helps mop up harmful free radicals and may support nerve metabolism. Typical research doses are in the hundreds of milligrams per day in adults, but exact dosing must be decided medically. Side effects can include stomach upset and low blood sugar, especially in people with diabetes. PMC+1
2. Acetyl-L-carnitine
Acetyl-L-carnitine helps transport fatty acids into mitochondria for energy production. Some small studies suggest it may support nerve regeneration and reduce pain in certain neuropathies. It is usually taken in divided doses. Possible side effects include nausea and restlessness. No strong trials exist in CMT2C, so it remains experimental and supportive only. PMC+1
3. Omega-3 fatty acids (fish oil)
Omega-3s from fish oil help build healthy cell membranes and have anti-inflammatory effects. They may support heart and brain health in CMT and reduce overall inflammation. Doses vary widely and must consider bleeding risk and interactions with blood-thinning medicines. Mild side effects include fishy aftertaste and stomach discomfort. PMC+1
4. Vitamin B complex (especially B1, B6, B12)
B vitamins are important for nerve health and energy production. In people with true deficiencies, replacing them can improve nerve function. However, very high doses, especially of B6, can actually damage nerves. For that reason, doctors usually check levels first and prescribe safe doses if needed, instead of high self-supplementation. PMC+1
5. Vitamin D
Vitamin D supports bone health, muscle function, and immune balance. Many people with limited mobility are deficient because they get less sunlight. Correcting low vitamin D with medical guidance can improve bone strength and reduce fracture risk. Too much vitamin D can damage kidneys and raise blood calcium, so supervised dosing is essential. PMC+1
6. Vitamin C (ascorbic acid)
Vitamin C has been studied as a possible therapy in CMT1A, but clinical trials did not show strong benefit. It still plays a general role in collagen formation and immune function. Normal dietary intake is usually enough; mega-doses are not recommended because they can cause kidney stones in some people. PMC+2PMC+2
7. Vitamin E
Vitamin E is a fat-soluble antioxidant that protects cell membranes from oxidative damage. In inherited vitamin E deficiency, replacing it is crucial to prevent neuropathy. In CMT2C there is no clear evidence of major benefit, but maintaining normal levels through diet or modest supplements may support general health. High doses can increase bleeding risk. PMC+1
8. Coenzyme Q10
CoQ10 helps mitochondrial energy production. It has been tried in some mitochondrial and muscle disorders. In theory, it may support energy in weakened muscles, but evidence in CMT is limited. Doses used in studies vary widely; side effects are usually mild (stomach upset), but interactions with blood thinners are possible. PMC+1
9. Magnesium
Magnesium is involved in muscle relaxation and nerve function. Correcting low magnesium may help cramps and twitching. However, high doses can cause diarrhoea and, in kidney disease, dangerous levels. Doctors often check blood levels before recommending supplements and adjust dose to age and kidney function. PMC+1
10. Curcumin (turmeric extract)
Curcumin is a natural anti-inflammatory compound from turmeric. In lab studies, it affects many signalling pathways linked to inflammation and oxidative stress. Human data in neuropathies are limited. It can interact with blood thinners and may cause digestive upset. If used, it should be at modest doses and only with medical approval. PMC+1
Immune-boosting, regenerative and stem-cell-related therapies
Key point: CMT2C is a genetic axonal neuropathy, not an autoimmune disease. Standard “immune-boosting” or immune-suppressing drugs are not routine treatments. Stem-cell and gene-based therapies for CMT are in research, not standard care. ScienceDirect+2PMC+2
1. Mesenchymal stem cell (MSC) therapy – experimental
Researchers are exploring MSCs from bone marrow or fat tissue as a way to support nerve repair. These cells release growth factors and may create a more healing-friendly environment around damaged nerves. So far, CMT data are early and mostly in animals or very small human studies. MSC treatments should only be received in approved clinical trials, not in unregulated private clinics.
2. Gene-based therapies (AAV or other vectors) – experimental
For some CMT types, scientists are testing gene-silencing or gene-replacement strategies using viral vectors like AAV. In theory, correcting or silencing the abnormal TRPV4 gene in CMT2C could prevent further nerve damage. At present, no such therapy is approved, and any use must stay inside formal trials because of safety and long-term risk questions. ScienceDirect+2Springer Link+2
3. Neurotrophic-factor-based therapies – experimental
Compounds that mimic natural nerve growth factors are being studied to see if they can protect axons in hereditary neuropathies. These drugs are designed to bind receptors on nerve cells and switch on survival pathways. Clinical use is still experimental and often limited by side effects or delivery problems. They are not routine treatments for CMT2C. ScienceDirect+1
4. Immunoglobulin or steroids (mainly for autoimmune neuropathies)
Intravenous immunoglobulin (IVIG) and steroids are standard treatments for acquired immune neuropathies such as CIDP, not for genetic CMT. In rare situations where a person has both CMT and an autoimmune neuropathy, these medicines might be used. They change immune activity, not the genetic cause, and can have serious side effects, so they are specialist decisions. ScienceDirect+1
5. Bone-marrow or hematopoietic stem cell transplant – research in other diseases
These transplants replace blood-forming cells and are used in some immune and metabolic diseases that affect nerves. They are not standard treatments for CMT2C, because the main defect is in peripheral nerves themselves. Transplants carry high risks and are only used when strong evidence shows benefit for a specific condition. ScienceDirect+1
6. Muscle-targeted drugs like NMD670 (see above) – research
Some experimental drugs target muscles rather than nerves. By making muscles respond better to weak nerve signals, they may partly overcome neuropathy. NMD670 is one example receiving orphan-drug designation for CMT, but it is still in trials and not yet available as normal treatment. Charcot-Marie-Tooth Disease+2CMT Research Foundation+2
Surgical treatments
Surgery in CMT2C does not treat the gene defect. It corrects structural problems caused by long-term muscle imbalance and nerve weakness. Decisions are made by experienced orthopaedic or ENT surgeons after careful assessment. medschool.cuanschutz.edu+3PMC+3cdn.fortunejournals.com+3
1. Foot deformity correction (soft-tissue releases and tendon transfers)
In many people, chronic muscle imbalance causes high-arched, twisted (cavovarus) feet and clawed toes. Surgeons can release tight tissues and move tendons to more balanced positions. This can improve foot shape, reduce pain, and make brace use and walking easier. It is usually done after non-surgical measures like braces have been tried. medschool.cuanschutz.edu+3PMC+3nmd-journal.com+3
2. Foot osteotomies and fusions
If deformities are rigid, bone-cutting procedures (osteotomies) and sometimes joint fusions may be needed. These operations realign bones to create a more stable, plantigrade (flat on the ground) foot. The goal is to improve function, fit shoes better, and reduce chronic pain, even if ankle movement becomes more limited. cdn.fortunejournals.com+2www.elsevier.com+2
3. Hand and wrist surgery (tendon transfers)
In severe hand weakness, surgeons may move stronger tendons to replace the action of paralyzed ones. For example, a tendon that still works can be attached to a finger that cannot extend. This can improve pinch, grip, and the ability to use tools or type. It is planned carefully to match each person’s pattern of weakness. PMC+1
4. Spinal surgery for scoliosis or deformity
Some people with CMT develop scoliosis or other spine curves that worsen balance or breathing. If bracing and physiotherapy are not enough, spinal fusion or other corrective surgery may be offered. These operations aim to straighten the spine, stabilise it, and protect lung function, but they are major procedures and need specialist centres. cdn.fortunejournals.com+1
5. Vocal cord surgery (medialisation, arytenoid procedures, laser cordectomy)
In CMT2C, vocal cord paralysis can cause breathing problems and weak voice. ENT surgeons may use operations like medialisation thyroplasty, arytenoid adduction, or endoscopic laser cordectomy to improve airway and voice. These procedures reposition or reshape the vocal cords so they meet or separate better, helping speech and sometimes breathing. Wikipedia+5PubMed+5JAMA Network+5
Prevention and lifestyle strategies
No one can fully prevent a genetic disease like CMT2C, but many steps can help reduce complications and preserve function:
Avoid nerve-toxic medicines where possible (some chemotherapy drugs, high-dose B6, and others) and always tell doctors you have CMT before new treatments. PMC+1
Protect your feet with well-fitting shoes, daily skin checks, and prompt care of blisters or cuts to prevent ulcers and infections. medschool.cuanschutz.edu+1
Keep active within safe limits using physiotherapy guidance to prevent deconditioning and stiffness. PMC+1
Use braces and aids early when recommended, instead of waiting until many falls have happened. Early support may prevent injuries. Pod NMD+1
Maintain a healthy weight to reduce strain on weak muscles and joints and lower the risk of diabetes. PMC+1
Do not smoke or vape, because smoking damages blood vessels and may worsen nerve health and wound healing. PMC+1
Stay up to date with vaccines, especially for flu and pneumonia, if you have breathing muscle weakness. cdn.fortunejournals.com+1
Manage other health problems, like diabetes, high blood pressure, and high cholesterol, because they can further harm nerves and blood supply. PMC+1
Plan pregnancies with genetic counselling if CMT2C is in your family. National Organization for Rare Disorders+1
Stay connected to CMT specialist clinics and registries so you can learn about new trials and standards of care. PMC+1
When to see doctors
You should see a doctor or specialist team urgently or promptly if:
You notice new or rapidly worsening weakness, especially if breathing, swallowing, or speaking suddenly change.
There are signs of breathing problems, such as waking up gasping, morning headaches, extreme daytime sleepiness, or shortness of breath at rest. cdn.fortunejournals.com+1
You develop choking, frequent coughing while eating, or sudden voice changes, which can suggest worsening vocal cord paresis. PubMed+2Wikipedia+2
You have repeated falls, fractures, or severe foot pain, because these may need braces or surgery. PMC+2medschool.cuanschutz.edu+2
You see skin breaks, ulcers, or infections on your feet or legs, especially if feeling is reduced.
Pain becomes uncontrolled despite medicines and therapy, or you notice new side effects like severe sleepiness or mood changes. PMC+1
You or your family have questions about genetic testing, family planning, or new research trials. National Organization for Rare Disorders+2Springer Link+2
What to eat and what to avoid
This is general advice; a dietitian can personalise it.
What to eat more of
Colourful fruits and vegetables for vitamins, minerals, and antioxidants that support immune and nerve health.
Lean protein (fish, eggs, beans, lean meat, tofu) to maintain muscles and repair tissues.
Whole grains (brown rice, oats, whole-wheat bread) for steady energy and fibre.
Healthy fats (olive oil, nuts, seeds, avocado) to support brain and nerve membranes.
Calcium- and vitamin-D-rich foods (dairy, fortified plant milks, small fish with bones) to keep bones strong when mobility is limited. PMC+1
What to limit or avoid
Sugary drinks and snacks, which add calories but no nutrients and increase diabetes risk.
Very processed fast foods high in salt and unhealthy fats, which worsen heart and vessel health.
Excess alcohol, which itself can damage nerves and worsen balance and falls. PMC+1
Very high-dose supplements without testing, especially vitamin B6, which can harm nerves at high levels. PMC+1
Crash diets or extreme restrictions, which can lead to muscle loss and low energy, making weakness and fatigue worse.
A balanced, enjoyable diet that you can stick to long term is usually better than any strict “miracle” diet.
Frequently asked questions (FAQs)
1. Is CMT2C always inherited from a parent?
CMT2C is usually autosomal dominant, so a person often has an affected parent. However, sometimes the TRPV4 mutation appears for the first time in a child (a new, or “de novo,” mutation). Genetic testing and counselling can clarify the pattern in each family. National Organization for Rare Disorders+2neurology.org+2
2. Can CMT2C be cured today?
At present, there is no cure and no approved drug that stops CMT2C. Treatment focuses on symptom control, preserving function, and preventing complications. Research into gene and muscle-targeted therapies is active, so future options may change, but nobody can promise a cure yet. CMT Research Foundation+3PMC+3PMC+3
3. Do all people with CMT2C develop breathing problems?
No. Some people mainly have leg and arm weakness, while others also develop vocal cord and diaphragm weakness. Doctors monitor breathing with lung-function tests and sleep studies when needed. Early detection allows earlier support such as non-invasive ventilation. JAMA Network+1
4. Will I need a wheelchair?
Many people with CMT2C walk for many years, especially with braces and physiotherapy. Some will use a wheelchair or scooter for long distances or as the disease progresses. Using aids is not a failure; it is a way to stay active and safe. PMC+2cmt.org.au+2
5. Can exercise make the disease worse?
Gentle, well-planned exercise is usually helpful and does not make the genetic problem worse. Extremely hard, unplanned exercise can cause overuse injuries and fatigue. Working with a physiotherapist to design a safe programme is the best way to stay active. PMC+2Lippincott Journals+2
6. Is there a special CMT2C diet?
There is no specific CMT2C diet proved to change the course of the disease. However, a healthy, balanced diet that maintains normal weight, supports muscles, and prevents diabetes is strongly recommended. This helps your overall health and resilience. PMC+2PMC+2
7. Are clinical trials worth considering?
Clinical trials are the way new treatments are tested. Joining a trial can give access to experimental drugs and close monitoring, but there are also risks and no guarantees. CMT-experienced neurologists and genetic counsellors can help you understand specific trial options. PMC+2CMT Research Foundation+2
8. Can CMT2C affect learning or intelligence?
CMT2C mainly affects peripheral nerves, not the brain. Most people have normal thinking and learning abilities. Any school or work problems are usually due to fatigue, physical limits, or hearing/voice problems, not reduced intelligence. Support and accommodations can make a big difference. National Organization for Rare Disorders+2Muscular Dystrophy Association+2
9. What is the difference between CMT2C and other CMT types?
CMT2C is an axonal form linked to TRPV4 mutations and is especially associated with vocal cord and diaphragm weakness. Other CMT types may involve demyelination, different genes, or different patterns of weakness and sensory loss. Genetic testing is needed to tell the exact subtype. Springer Link+3National Organization for Rare Disorders+3Muscular Dystrophy Association+3
10. How often should I see my doctors?
Most people benefit from regular reviews with a neurologist and rehabilitation team, often once or twice a year, plus extra visits if problems arise. Breathing issues, rapid changes, or new pain should prompt earlier review. Your schedule will be tailored to your age and disease severity. PMC+2PMC+2
11. Can children with CMT2C play sports?
Many children can take part in adapted sports and physical education. Activities like swimming and cycling are usually safer than high-impact contact sports. The key is supervision, proper braces or shoes, and regular checks to avoid injuries. A paediatric neurologist and physiotherapist can guide safe choices. PMC+2Physiopedia+2
12. Will my symptoms always get worse?
CMT2C is generally slowly progressive, but the speed varies widely. Some people have mild problems for decades; others are more affected. Good supportive care, early therapy, and active complication prevention can help maintain quality of life even though the underlying gene change remains. PMC+2National Organization for Rare Disorders+2
13. Are there warning signs of serious breathing trouble?
Yes. Signs include waking up gasping, severe morning headaches, very restless sleep, feeling extremely sleepy in the day, blue lips, or sudden shortness of breath at rest. These symptoms need immediate medical attention and often urgent respiratory assessment. cdn.fortunejournals.com+1
14. Can I choose not to have genetic testing?
Yes. Genetic testing is a personal choice. Some people want a clear answer and to know their risk to children; others feel it would increase anxiety. A genetic counsellor can explain pros and cons and support whichever choice feels right for you and your family. National Organization for Rare Disorders+1
15. Where can I find reliable information and support?
National and international CMT organisations, neuromuscular clinics, and patient registries offer trustworthy information, support groups, and research news. Hospital neurology departments often know local resources. Be careful with random internet sources or “miracle cure” claims, and always check major treatment decisions with your healthcare team. cmt.org.au+2CMT Research Foundation+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 22, 2025.
