Charcot-Marie-Tooth disease axonal type 2C (CMT2C) is a rare inherited nerve disease. It mainly damages the long nerves that control movement and feeling in your arms and legs. Doctors call this an “axonal sensorimotor neuropathy,” which means the main problem is in the axon (the long wire part) of the nerve, and both movement (motor) and feeling (sensory) are affected. CMT2C is usually passed down in an autosomal dominant way, which means a person needs only one changed copy of the gene from one parent to get the disease.National Organization for Rare Disorders+1
Charcot-Marie-Tooth disease axonal type 2C (CMT2C) is a rare inherited nerve disease that mainly damages the long nerves of the arms and legs and also often affects the voice and breathing muscles. It is usually caused by harmful changes (mutations) in the TRPV4 gene, which makes an ion channel that controls calcium movement in cells. When TRPV4 does not work properly, nerve cells become stressed and slowly lose function, leading to weakness, numbness, and problems with balance and walking.PubMed+1
CMT2C is passed on in an autosomal dominant pattern, which means a person can develop the disease if they inherit one faulty copy of the gene from either parent. Symptoms can start in childhood or later life and often include weakness in the legs and hands, high-arched feet, hand deformities, and, in this type, vocal cord weakness, breathing problems from diaphragm weakness, and sometimes hearing loss.National Organization for Rare Disorders+1
In CMT2C, weakness is often seen in the legs, arms, and hands, and there can also be problems with the voice and breathing. This happens because the nerves to the vocal cords and the breathing muscle (the diaphragm) can also be involved. Over time, muscles may become thin and wasted, and walking can become difficult. CMT2C usually gets worse slowly over many years, but the speed can be different from person to person.PubMed+1
Other Names
Doctors and researchers may use several other names for Charcot-Marie-Tooth disease axonal type 2C. Knowing these names helps you recognize the same condition in different articles or reports:
Charcot-Marie-Tooth disease type 2C (CMT2C)PubMed
Axonal Charcot-Marie-Tooth disease type 2CNational Organization for Rare Disorders+1
TRPV4-related Charcot-Marie-Tooth disease (because changes in the TRPV4 gene cause it)PubMed+1
Hereditary motor and sensory neuropathy type 2C (HMSN2C)ScienceDirect
TRPV4-linked axonal neuropathy (when doctors talk about the broader group of TRPV4 nerve diseases, including CMT2C)Europe PMC+1
All of these terms refer to the same basic problem: a genetic change in TRPV4 that damages long nerves and often affects the vocal cords and breathing muscles.PubMed+1
Types
CMT2C itself is one genetic subtype inside the larger family of Charcot-Marie-Tooth diseases. CMT is divided into many types based on what the nerve looks like under tests and which gene is changed. CMT2C is one of the “type 2” forms, which are mainly axonal (the axon is the main damaged part, not the myelin covering).Wikipedia+1
Within TRPV4-related disease, doctors sometimes talk about different clinical patterns that may overlap with CMT2C:
Classic CMT2C pattern – weakness and wasting of lower legs and feet, later hands, plus problems in the vocal cords and diaphragm.PubMed+1
Scapuloperoneal pattern – weakness of shoulder-girdle muscles (around shoulder blades) and lower leg muscles; this pattern can overlap with CMT2C in some families.PMC+1
TRPV4 neuromuscular spectrum – some people mainly have peripheral neuropathy (CMT2C), some have spinal muscular atrophy type signs, and some have mixed features within one family, depending on how the same gene mutation affects nerve cells.Europe PMC+2Grantome+2
Even though these patterns look different, they are all linked to mutations in the same TRPV4 gene, so doctors see them as part of a single disease spectrum.Grantome+1
Causes
1. Mutation in the TRPV4 gene
The main direct cause of CMT2C is a harmful change (mutation) in the TRPV4 gene on chromosome 12. This gene tells the body how to make a special ion channel that controls the flow of calcium into cells. When TRPV4 is mutated, the channel does not work normally and becomes overactive. This abnormal activity slowly damages the nerve cells, especially the long axons.PubMed+2Grantome+2
2. Autosomal dominant inheritance
CMT2C is usually inherited in an autosomal dominant way. This means that if one parent has a TRPV4 mutation, each child has a 50% chance of inheriting it. The disease can appear in many members of the same family across several generations. This pattern is a key clue for doctors that the disease is genetic.PubMed+1
3. De novo (new) TRPV4 mutation
Sometimes a child develops CMT2C even though neither parent has symptoms. In these cases, the mutation arises for the first time in the egg or sperm, or very early after conception. This is called a de novo mutation. Once the child has the mutation, they can pass it on to their own children.neurology.org+1
4. TRPV4 channel overactivity and calcium overload
Mutant TRPV4 channels often stay more open than normal. This lets too much calcium enter the nerve cell. Extra calcium can stress and poison the cell, damaging key structures inside and triggering cell death pathways. Over time, this leads to axonal degeneration.PMC+2Nature+2
5. Axonal degeneration of motor nerves
Because the axon is long and needs constant support, it is very sensitive to stress. In CMT2C, the axon of motor nerves slowly degenerates, especially those going to the muscles of the feet, legs, hands, and diaphragm. This degeneration leads to weakness and muscle wasting.National Organization for Rare Disorders+1
6. Axonal degeneration of sensory nerves
CMT2C also affects sensory nerves, which carry feelings of touch, vibration, and position back to the brain. Damage to these axons causes numbness, tingling, and poor balance, because the brain cannot “feel” where the feet and hands are in space.National Organization for Rare Disorders+2Europe PMC+2
7. Impaired mitochondrial transport in axons
Research suggests that TRPV4 mutations can disturb how mitochondria (the energy factories) move along the axon. When mitochondria cannot reach distant parts of the nerve, those areas do not receive enough energy, which makes the axon more likely to degenerate.Nature+1
8. Cytotoxicity from abnormal TRPV4 signaling
Mutant TRPV4 channels increase calcium flow and change signaling inside the cell. This can trigger cell stress and eventually cell death (cytotoxicity). Studies in cell models show that these mutant channels are more toxic than normal ones, supporting this mechanism as a cause of nerve damage.PMC+2Pure+2
9. Length-dependent vulnerability of nerves
Long nerves are harder to maintain than short nerves. They require constant transport of proteins and energy. In CMT2C, this length-dependent stress means nerves to the feet, legs, and hands are affected first and most severely, because they are longest.National Organization for Rare Disorders+1
10. Involvement of phrenic nerve (to diaphragm)
The phrenic nerve controls the diaphragm, the main breathing muscle. TRPV4-related axonal damage can involve this nerve, leading to weakness of the diaphragm and trouble breathing, especially when lying flat or during sleep.PubMed+2Europe PMC+2
11. Involvement of laryngeal nerves (to vocal cords)
CMT2C often affects the nerves that move the vocal cords. Damage to these nerves weakens or paralyzes the vocal cords. This causes hoarse voice, weak voice, or breathing noise (stridor) when air passes through partly closed cords.PubMed+2Charcot-Marie-Tooth Disease+2
12. Genetic background and modifier genes
Even with the same TRPV4 mutation, some people have mild disease and others have more severe problems. Researchers think that other genes in a person’s background can modify how strongly the mutation acts. These “modifier” genes are a cause of the wide variation in symptoms within families.Europe PMC+1
13. Environmental stress on nerves
Nerves already weakened by CMT2C may be more sensitive to environmental stresses. For example, repeated small injuries, long-term pressure on nerves, or severe infections may worsen nerve damage. These factors do not cause CMT2C alone, but they can add to the damage caused by the TRPV4 mutation.Wikipedia
14. Metabolic or nutritional strain
Poor overall health, such as uncontrolled diabetes, severe vitamin deficiency, or poor nutrition, may further harm already fragile nerves. In a person with CMT2C, such metabolic stress can make weakness and numbness worse, even though it is not the original cause of the disease.Wikipedia
15. Abnormal response to mechanical stress
TRPV4 channels are normally activated by mechanical and osmotic changes. Mutant channels may respond abnormally to mechanical stress (such as everyday joint movement or small injuries), which can add extra stress to the nerve cells and make axonal damage progress.Wikipedia+1
16. Osmotic and temperature sensitivity
TRPV4 also reacts to changes in osmotic pressure and warm temperatures. Abnormal channel behavior may mean that normal body fluid changes or mild heat can trigger extra calcium flow into neurons, adding to cell stress and injury over time.Wikipedia
17. Inflammation-related sensitization of TRPV4
Inflammation in the body can make TRPV4 channels more sensitive. In a person with mutant TRPV4, episodes of inflammation (for example, infections) might further boost channel activity and worsen nerve injury.Wikipedia+1
18. Age-related nerve vulnerability
As people age, nerves naturally become less resilient. In someone with CMT2C, this age-related decline combines with the genetic problem, making symptoms slowly worse with age, such as greater weakness and balance problems in adulthood.Wikipedia
19. Respiratory complications
Weak diaphragm and chest muscles can lead to low oxygen at night and repeated chest infections. These breathing problems do not cause CMT2C, but they can worsen fatigue and overall health, adding to the impact of nerve damage.OUP Academic+1
20. Skeletal and joint changes from chronic weakness
Long-term weakness can change the shape of the feet, spine, and joints. These skeletal changes (like high arches and hammertoes) put extra strain on nerves and muscles. This mechanical stress can make walking harder and may speed up functional decline, although it is a result rather than the original cause of nerve disease.Wikipedia+1
Symptoms
1. Weakness in feet and lower legs
One of the first symptoms is often weakness in the muscles that lift the front of the foot. People may notice they trip more, drag their toes, or feel that their ankles are weak and unstable. This happens because the long nerves to these muscles are damaged.Wikipedia+1
2. Foot drop and high-stepping gait
Because the front of the foot is weak, the toes can point downward when walking. To avoid tripping, people lift their knees higher with each step. This is called a high-stepping gait or “steppage gait,” and it is very typical of many forms of CMT, including CMT2C.Wikipedia
3. Muscle wasting in legs and feet
Over time, the muscles in the lower legs and feet become thin and wasted. The legs may look like an “inverted champagne bottle” – thin below the knees and more normal above. This is due to long-term loss of motor nerve supply to those muscles.Wikipedia+1
4. Weakness in hands and arms
Later in the disease, weakness often spreads to the hands and sometimes the arms. People may have trouble with fine tasks such as buttoning clothes, writing, or holding small objects. Grip may feel weak, and objects may be dropped more easily.National Organization for Rare Disorders+2Charcot-Marie-Tooth Disease+2
5. Numbness and reduced feeling
Many people with CMT2C feel numbness or reduced sensation in their feet and hands. They may not feel light touch, vibration, or the sense of where their joints are. This can make it hard to walk on uneven ground or to feel small objects with the fingers.National Organization for Rare Disorders+2Lippincott Journals+2
6. Tingling and burning sensations
Some patients experience tingling, pins-and-needles, or burning pain in the feet and hands. These uncomfortable sensations happen because damaged sensory nerves fire in an abnormal way, sending false signals to the brain.Wikipedia
7. Balance problems and frequent falls
Because both strength and sensation in the legs are reduced, balance becomes poor. People may sway when standing with their feet together or with eyes closed, and they may fall more easily, especially in the dark or on uneven ground.Wikipedia+1
8. Foot deformities (high arches and hammertoes)
Over time, the muscle imbalance in the foot causes the arch to become very high (pes cavus) and the toes to curl (hammertoes). These changes can cause pain, pressure points, and difficulty finding comfortable shoes.Wikipedia+1
9. Reduced or absent reflexes
Reflexes, such as the ankle jerk that doctors test with a hammer, are often weak or absent in CMT2C. This is because the reflex loop needs healthy sensory and motor nerves, and both are damaged in this disease.Wikipedia+1
10. Hoarse or weak voice
In CMT2C, the nerves that control the vocal cords can be affected. This may cause hoarseness, a breathy or weak voice, or difficulty speaking loudly. Some people notice voice problems very early, even before severe leg weakness.PubMed+2Charcot-Marie-Tooth Disease+2
11. Noisy breathing or shortness of breath
If the vocal cords do not open fully, breathing can be noisy (stridor). When the diaphragm is weak, breathing becomes hard when lying flat, during exercise, or during sleep. People may feel short of breath or wake up at night gasping.OUP Academic+2PubMed+2
12. Fatigue and reduced stamina
Because muscles are weak and breathing may be less efficient, people with CMT2C can feel tired more easily. Tasks that used to be simple, like walking long distances or climbing stairs, can cause fatigue and may need more rest breaks.cmtausa.org+1
13. Hearing problems (in some patients)
Some people with TRPV4-related neuropathies, including CMT2C, can develop hearing loss. This may be due to nerve problems in the auditory pathway. The degree of hearing loss can vary, and not everyone is affected.cmtausa.org+1
14. Skeletal problems (scoliosis or joint issues)
Weakness and imbalance of muscles supporting the spine and joints can lead to scoliosis (curved spine) or joint problems. These skeletal issues may add to pain and posture difficulties in daily life.Wikipedia+1
15. Emotional and social impact
Living with a chronic, progressive nerve disease can cause emotional stress, anxiety, or low mood. Difficulties with walking, speaking, or breathing can affect school, work, and social life. Support from family, friends, and health professionals is very important.cmtausa.org+1
Diagnostic Tests
Physical exam tests
1. General neurological examination
The neurologist looks at muscle strength, tone, and bulk in the arms and legs, checks reflexes, and tests sensation (touch, vibration, temperature, and joint position). In CMT2C, the doctor often finds distal weakness, muscle wasting, loss of vibration and position sense, and reduced or absent ankle reflexes.National Organization for Rare Disorders+2Lippincott Journals+2
2. Gait and posture assessment
The doctor watches how the person stands and walks, looking for a high-stepping gait, foot drop, ankle instability, or wide-based stance. They may also check for scoliosis or other postural changes. These findings point toward a chronic neuropathy such as CMT2C.Wikipedia+1
3. Muscle strength grading
Muscle groups in the feet, legs, hands, and arms are tested one by one and graded for strength. In CMT2C, distal muscles (farther from the body) are usually weaker than proximal muscles (closer to the body). This pattern helps distinguish peripheral neuropathy from muscle diseases.Lippincott Journals+1
4. Sensory testing
The doctor tests light touch, pinprick, vibration (using a tuning fork), and joint position sense in the toes and fingers. People with CMT2C often show reduced vibration and position sense in the feet and sometimes in the hands, which confirms sensory nerve involvement.National Organization for Rare Disorders+2Lippincott Journals+2
5. Reflex testing
Deep tendon reflexes (such as knee and ankle jerks) are checked with a reflex hammer. In CMT2C, these reflexes are usually reduced or absent, especially at the ankles, supporting the diagnosis of a peripheral neuropathy rather than a brain or spinal cord disease.Wikipedia+1
Manual (bedside functional) tests
6. Heel-walking and toe-walking
The person is asked to walk on their heels and then on their toes. Weakness in ankle dorsiflexors (lifting the foot) makes heel-walking difficult, while weakness in calf muscles makes toe-walking hard. Difficulty here suggests distal muscle weakness seen in CMT2C.Wikipedia+1
7. Romberg test
The person stands with feet together, first with eyes open, then closed. If they become much more unsteady with eyes closed, it suggests loss of position sense in the legs. This pattern is common in sensory neuropathies like CMT2C.Wikipedia+1
8. Manual muscle testing of hand grip and pinch
The examiner tests grip strength and pinch between thumb and fingers by hand. Weakness in these actions in a person with leg symptoms supports involvement of distal upper limb muscles, which is common as CMT2C progresses.Lippincott Journals+1
9. Contracture and joint range testing
The doctor gently moves the ankles, knees, and fingers to look for tight tendons or joint contractures. In long-standing CMT2C, Achilles tendon tightness and foot deformities are common. These physical findings help show how advanced the disease is.Wikipedia+1
10. Bedside respiratory tests (simple)
Simple tests like counting out loud on one breath or checking how far the abdomen moves with breathing can suggest diaphragmatic weakness. If breathing seems shallow or limited, more formal respiratory tests are ordered.OUP Academic+1
Lab and pathological tests
11. Basic blood tests to rule out other neuropathies
Doctors often order blood tests such as glucose, vitamin B12, thyroid function, kidney and liver tests, and sometimes immune blood tests. These are usually normal in CMT2C, but they help rule out other treatable causes of neuropathy before confirming a genetic cause.Wikipedia
12. Genetic testing for TRPV4 mutations
This is the key confirmatory test. DNA is taken from blood or saliva and analyzed for mutations in the TRPV4 gene. Finding a known disease-causing mutation in a person with typical symptoms confirms the diagnosis of CMT2C. Panel tests that include many CMT genes are often used.PubMed+2Wikipedia+2
13. Broader CMT gene panel or exome testing
If standard TRPV4 testing is negative but CMT2C is still suspected, a larger gene panel or whole-exome sequencing may be done. This helps discover rare or new mutations and also checks for other CMT subtypes. This approach is now widely used in inherited neuropathies.pfmjournal.org+1
14. Nerve biopsy (rarely needed)
In some unclear cases, a small piece of a sensory nerve (often from the lower leg) may be removed and examined under a microscope. In CMT2C, the pathologist usually sees signs of axonal loss rather than demyelination. Today, biopsy is used less often because genetic testing is more precise.National Organization for Rare Disorders+1
15. Muscle biopsy (only in difficult cases)
If the diagnosis is uncertain and doctors need to tell neuropathy from a primary muscle disease, they may take a small muscle sample. In CMT2C, the muscle biopsy shows changes of denervation (loss of nerve supply), not a primary muscle disorder. This supports a nerve problem.Lippincott Journals+1
Electrodiagnostic tests
16. Nerve conduction studies (NCS)
NCS measure how fast and how strongly electrical signals travel along nerves. In CMT2C, conduction speed is often near normal or only mildly slowed, but the size of the response (amplitude) is reduced, which fits with axonal neuropathy. This pattern helps separate CMT2C from demyelinating types like CMT1.Europe PMC+2pfmjournal.org+2
17. Electromyography (EMG)
Needle EMG looks at the electrical activity in muscles. In CMT2C, EMG shows signs of chronic denervation and re-innervation (long-standing nerve damage with some nerve regrowth). EMG can also detect involvement of the diaphragm and other respiratory muscles.Europe PMC+2Lippincott Journals+2
18. Repetitive nerve stimulation or specialized studies (if needed)
In special cases, extra electrodiagnostic tests may be done to rule out disorders of the neuromuscular junction or motor neuron disease. Normal results on these tests with abnormal NCS/EMG consistent with axonal neuropathy further support a diagnosis of CMT2C.pfmjournal.org+1
Imaging tests
19. Imaging of the diaphragm and chest (X-ray, ultrasound, or fluoroscopy)
Imaging can show an elevated diaphragm if it is weak on one or both sides. Chest X-ray, fluoroscopy (“sniff test”), or ultrasound can all be used. These tests help confirm that breathing problems are due to diaphragmatic weakness from nerve involvement, as seen in CMT2C.OUP Academic+2pfmjournal.org+2
20. Laryngoscopy for vocal cords
An ear, nose, and throat specialist may perform laryngoscopy by passing a thin scope through the nose or mouth to view the vocal cords. In CMT2C, this can show vocal cord paresis (weakness) or paralysis. This test confirms that hoarseness and breathing noise are due to nerve-related vocal cord problems.OUP Academic+2Charcot-Marie-Tooth Disease+2
Non-Pharmacological Treatments (Therapies and Others)
There is strong evidence that non-drug therapies are the foundation of care for Charcot-Marie-Tooth disease axonal type 2C. They help maintain function, reduce complications, and improve daily life even though they cannot change the underlying gene problem.PMC+2Scientia Salut+2
Individualized physical therapy
Physical therapy uses stretching, strengthening, and balance exercises to keep muscles working as well as possible and to prevent joint stiffness. A therapist familiar with CMT designs a safe program that focuses on ankle stability, hip and core strength, and gait training. Regular sessions and a home program can slow loss of mobility, reduce falls, and support better posture and energy use.Charcot-Marie-Tooth Association+2Physiopedia+2Occupational therapy for daily activities
Occupational therapists help people adapt everyday tasks such as dressing, cooking, writing, and computer use. They can suggest special tools like built-up pens, button hooks, and kitchen aids to compensate for weak hands. Training in joint protection and energy conservation helps people perform tasks with less pain and fatigue, making work, school, and self-care more manageable.Charcot-Marie-Tooth Association+1Ankle-foot orthoses (AFOs) and other braces
Lightweight braces, especially AFOs, can support weak ankle muscles, prevent foot drop, and improve walking safety. Orthotic devices can also correct or support high-arched feet and unstable ankles, helping to reduce falls and joint strain. An orthotist adjusts the fit as muscles change over time. Wearing the right brace often makes walking smoother and less tiring.ScienceDirect+1Custom footwear and insoles
Special shoes and insoles help distribute pressure more evenly on the feet and accommodate deformities like high arches, claw toes, or hammer toes. Good footwear can reduce calluses, ulcers, and pain, and improve stability when standing and walking. A podiatrist or orthotist can prescribe shoes with wide toe boxes, firm heels, and soft insoles to protect fragile skin and joints.ScienceDirect+1Respiratory therapy and breathing support
Because CMT2C can weaken the diaphragm and chest muscles, regular checks of breathing function are important. Respiratory therapists may recommend breathing exercises, airway clearance techniques, or non-invasive ventilation at night if needed. Early support can improve sleep quality, reduce morning headaches and fatigue, and lower the risk of chest infections.Charcot-Marie-Tooth Association+1Speech and voice therapy
Vocal cord weakness is a key feature of CMT2C. Speech-language therapists can teach breathing and vocal techniques that help make the voice clearer and reduce strain. They also help people manage swallowing problems if they occur. Simple strategies such as pausing while speaking, pacing conversations, and using amplifying devices can improve communication and confidence.Charcot-Marie-Tooth Disease+1Balance and gait training
Targeted exercises to improve balance, coordination, and walking pattern can reduce falls and fear of falling. Therapists may use treadmill walking, stepping tasks, and balance boards to challenge the nervous system in a controlled way. Training often includes practicing safe turning, stair climbing, and walking on uneven ground to prepare for real-life situations.MDPI+1Aquatic (water-based) therapy
Exercising in warm water reduces stress on weak joints and allows safer practice of movements that are difficult on land. Water supports the body, making it easier to walk, stretch, and strengthen muscles. Aquatic therapy can help people with CMT2C increase endurance and flexibility while reducing pain and fear of falling.MDPI+1Strength and endurance training
Low-to-moderate intensity resistance training and aerobic exercise, such as cycling or walking, can help maintain muscle mass and cardiovascular fitness without overworking fragile nerves. Exercise plans should be supervised at first to avoid over-fatigue. Regular activity may improve mood, energy, and overall health.PMC+2MDPI+2Stretching and contracture prevention
Daily stretching of ankles, calves, hamstrings, and finger joints helps prevent tightness and contractures that can worsen deformities and limit mobility. Therapists may teach gentle stretches, night splints, and positioning techniques. These simple routines can greatly affect long-term joint comfort and function.Charcot-Marie-Tooth Association+1Foot care and podiatry
Regular foot checks, nail care, and treatment of calluses and corns help prevent ulcers and infections, especially since many people with CMT have reduced sensation. Podiatrists may trim nails safely, advise on socks and shoes, and treat early skin problems before they become serious. Good foot care is a key part of long-term self-management.Scientia Salut+1Pain psychology and cognitive-behavioural therapy (CBT)
Chronic nerve pain and disability can cause anxiety, low mood, and sleep problems. Psychologists or pain specialists can teach coping skills, relaxation, pacing, and CBT techniques to change how the brain responds to pain. These tools do not remove pain but often make it feel more manageable and reduce its impact on daily life.PMC+1Energy conservation and fatigue management
People with CMT2C often fatigue easily because weak muscles work harder to perform tasks. Occupational therapists teach ways to plan the day, alternate heavy and light activities, sit instead of stand when possible, and use wheeled carts or other aids. Managing fatigue protects muscles and can extend the time someone can work or study.Dove Medical Press+1Assistive devices for mobility
Canes, trekking poles, walkers, and wheelchairs can be introduced as needed to maintain independence and safety. Using a device is not a failure; it is a tool that allows longer distances, faster speeds, and safer community participation. Choosing the right device depends on strength, balance, and daily environments.PMC+1Home safety and fall-prevention modifications
Simple changes at home, such as removing loose rugs, improving lighting, installing grab bars, and using non-slip mats, can greatly reduce falls. Occupational therapists can perform home visits to identify hazards and suggest low-cost solutions that make moving around safer and easier.Scientia Salut+1Vocational and school rehabilitation
Vocational counsellors and occupational therapists can support work or school planning by suggesting ergonomic adjustments, flexible schedules, or role modifications. Early planning helps people stay employed or continue education while respecting energy limits and physical abilities. Employers and schools often can provide reasonable accommodations when informed.PMC+1Genetic counseling for individuals and families
Genetic counselors explain how CMT2C is inherited, what the chances are of passing it on, and what reproductive options exist. They also provide emotional support when families are deciding about testing children or planning pregnancies. This information can help families make informed, personal choices.National Organization for Rare Disorders+1Psychological counseling and peer support groups
Living with a long-term progressive condition can be emotionally hard. Counselling and peer groups offer a safe space to share fears, frustrations, and coping strategies. Feeling understood and connected often reduces loneliness and boosts motivation for self-care and rehabilitation.PMC+1Respiratory and sleep monitoring
Regular sleep studies and lung function tests are important when the diaphragm or vocal cords are weak. Monitoring helps detect early breathing problems, sleep apnea, or low oxygen levels. Early treatment, such as CPAP or BiPAP, can improve daytime alertness and protect heart and brain health.Charcot-Marie-Tooth Association+1Education and self-management training
Education about CMT2C, including safe activity levels, warning signs of complications, and realistic expectations, helps people take an active role in their care. Written resources, reputable websites, and teaching sessions empower patients and families to work well with the healthcare team and avoid harmful misinformation.Actio Biosciences+1
Drug Treatments – Medicines Used for Symptom Control
There is no medicine approved specifically to cure Charcot-Marie-Tooth disease axonal type 2C. Drug treatments focus on controlling neuropathic pain, muscle stiffness, mood changes, and other symptoms. All medicines and doses must be chosen by a neurologist or pain specialist; this is especially important if you are under 18.PMC+2ScienceDirect+2
Gabapentin (Neurontin and generics)
Gabapentin is an anticonvulsant medicine approved for conditions like postherpetic neuralgia and seizures, and it is widely used off-label for neuropathic pain in CMT. It reduces overactive pain signaling by binding to certain calcium channel subunits in nerve cells. Common side effects include dizziness, sleepiness, and swelling. The dose is started low and increased slowly under medical supervision.FDA Access Data+2FDA Access Data+2Extended-release gabapentin (Gralise, Horizant)
Extended-release forms of gabapentin provide more even blood levels with once-daily or evening dosing, which may help night pain or restless legs. They are approved for postherpetic neuralgia and restless legs syndrome in adults. Side effects are similar to standard gabapentin and include sleepiness and dizziness. Doctors choose the formulation and schedule based on symptom pattern and kidney function.FDA Access Data+2FDA Access Data+2Pregabalin (Lyrica, Lyrica CR)
Pregabalin is an anticonvulsant and neuropathic pain medication approved for diabetic nerve pain, postherpetic neuralgia, spinal cord injury pain, and fibromyalgia. It binds to similar calcium channel targets as gabapentin but with different pharmacokinetics. It can reduce burning, shooting, and tingling pain. Dizziness, weight gain, and swelling are common side effects, and the dose is carefully titrated.FDA Access Data+2FDA Access Data+2Duloxetine (Cymbalta)
Duloxetine is a serotonin-noradrenaline reuptake inhibitor (SNRI) approved for diabetic peripheral neuropathic pain, major depression, anxiety, and chronic musculoskeletal pain. It increases serotonin and noradrenaline in pain pathways, which helps dampen pain signals and improve mood. Side effects may include nausea, dry mouth, sweating, and sleep changes. It is taken once or twice daily and should not be stopped suddenly.FDA Access Data+2FDA Access Data+2Amitriptyline
Amitriptyline is a tricyclic antidepressant that has long been used in low doses for chronic neuropathic pain and sleep problems. It blocks reuptake of serotonin and noradrenaline and also acts on other receptors that reduce pain sensitivity. It can cause dry mouth, constipation, weight gain, and drowsiness, so it is usually taken at night. Careful monitoring is needed because high doses increase heart rhythm risks.FDA Access Data+1Nortriptyline
Nortriptyline is another tricyclic antidepressant often used when amitriptyline is not tolerated. It has similar pain-relieving mechanisms but may cause slightly fewer sedating and anticholinergic side effects in some people. Doctors start with a low bedtime dose and adjust slowly while checking for mood changes, heart rhythm issues, and interactions with other medicines.FDA Access DataVenlafaxine
Venlafaxine is an SNRI antidepressant that can help neuropathic pain and anxiety or depression that sometimes accompany chronic nerve disease. It increases serotonin and noradrenaline in the brain and spinal cord. Side effects may include nausea, increased blood pressure, and sleep disturbance. Doses are gradually adjusted, and it should not be stopped abruptly to avoid withdrawal symptoms.PMC+1Topical lidocaine patch or gel
Lidocaine patches or gels numb the skin over painful areas by blocking sodium channels in nerve endings. They are useful for localized burning or shooting pain, especially on the feet or shins. Side effects are usually mild and limited to skin irritation. They can be combined with oral medicines and provide targeted pain relief without strong systemic effects.Scientia Salut+1Topical capsaicin cream or high-dose patch
Capsaicin, derived from chili peppers, depletes certain pain-signaling chemicals from nerve endings. Low-dose creams can be applied at home, while high-dose patches are placed in clinics. The main side effect is burning or stinging at the application site, which usually decreases with repeated use. It may help focal neuropathic pain in some people with CMT.ScienceDirect+1Non-steroidal anti-inflammatory drugs (NSAIDs)
Drugs like ibuprofen or naproxen do not directly treat nerve pain but can relieve musculoskeletal pain, joint strain, and headaches that arise from altered walking patterns and posture. They work by reducing prostaglandin production and inflammation. Long-term use can irritate the stomach and affect kidneys or blood pressure, so they should be used at the lowest effective dose and under medical guidance.Dove Medical Press+1Paracetamol (acetaminophen)
Paracetamol can help mild to moderate musculoskeletal or general pain in CMT2C, especially when NSAIDs are not suitable. It works centrally to reduce pain and fever but does not have strong anti-inflammatory effects. The main safety concern is liver damage at high doses, so total daily intake must stay within recommended limits.Scientia Salut+1Baclofen
Baclofen is a muscle relaxant that acts on GABA-B receptors in the spinal cord to reduce spasticity and muscle cramps. In some people with CMT2C who develop spasticity or painful stiffness, baclofen can ease movement and improve sleep. Side effects include drowsiness, weakness, and dizziness. It must be tapered slowly if stopped to avoid withdrawal symptoms.FDA Access Data+2FDA Access Data+2Tizanidine
Tizanidine is another muscle relaxant that works through alpha-2 adrenergic receptor activity to reduce muscle tone. It can help painful muscle tightness but often causes sleepiness and low blood pressure. Doctors usually start with small night doses and watch for liver function changes and drug interactions.Dove Medical Press+1Botulinum toxin injections
Botulinum toxin can be injected into overactive muscles to reduce spasticity or painful deformities in the feet and ankles. It blocks acetylcholine release at the neuromuscular junction, leading to temporary relaxation of the targeted muscles. The effect lasts several months, and side effects depend on injection site, such as localized weakness.Dove Medical Press+1Short-term tramadol
Tramadol is a weak opioid with additional serotonin and noradrenaline reuptake effects, sometimes used for short periods when pain flares are severe and other drugs are not enough. It must be used carefully because it can cause nausea, dizziness, constipation, and dependence. It is generally avoided for long-term daily use, especially in young people.Dove Medical Press+1Selective serotonin reuptake inhibitors (SSRIs)
SSRIs such as sertraline or fluoxetine do not directly treat nerve pain but can help depression and anxiety linked with chronic illness. Better mood often improves pain coping and participation in therapy. Side effects may include gastrointestinal upset, sleep changes, or sexual dysfunction. Dose and choice depend on past history and other medicines.PMC+1Sleep medicines when needed
For people with severe insomnia despite non-drug approaches, doctors may prescribe short-acting sleep aids for limited periods. These can help break a cycle of pain and poor sleep but must be used cautiously because of risks of dependence and daytime drowsiness. Non-drug sleep strategies are always tried first.Scientia Salut+1Treatment of associated breathing or heart problems
If CMT2C affects breathing or leads to complications such as sleep apnea or heart strain, doctors may prescribe inhalers, diuretics, or other cardiopulmonary medicines. These drugs do not treat the neuropathy itself but can greatly improve comfort and survival. Detailed choices depend on test results from respiratory and cardiac specialists.Charcot-Marie-Tooth Association+1Treatment of osteoporosis or bone health issues
Long-term weakness and reduced mobility can lead to bone loss. Doctors may prescribe vitamin D, calcium, or bone-protective medicines such as bisphosphonates when needed. Maintaining bone strength reduces fracture risk after falls, which is especially important in people with unstable gait.PMC+1Experimental TRPV4 inhibitor ABS-0871 (research setting only)
ABS-0871 is an experimental small-molecule inhibitor of TRPV4 currently being studied in a phase 1 trial for CMT2C and TRPV4-related bone disease. It aims to calm the overactive TRPV4 channel and reduce nerve damage at its root. This drug is not yet approved; it is given only in tightly controlled clinical trials.Actio Biosciences+2Actio Biosciences+2
Dietary Molecular Supplements
Dietary supplements cannot cure CMT2C, and evidence is often limited or indirect. They should be seen as supportive tools alongside medical and rehabilitation care and always discussed with a doctor to avoid interactions.
Alpha-lipoic acid – An antioxidant studied in diabetic neuropathy that may reduce oxidative stress in nerves and improve burning pain in some people. It works by scavenging free radicals and improving mitochondrial function. Typical use is as an oral capsule once or twice daily, but dosing and safety must be supervised, particularly in people with thyroid or blood sugar issues.PMC+1
Acetyl-L-carnitine – This molecule helps mitochondria use fatty acids for energy and may support nerve repair in some neuropathies. It is usually taken in capsule form, with doses spread through the day. Possible benefits include slightly improved nerve conduction and reduced pain. Mild nausea or restlessness can occur, so medical monitoring is important.PMC+1
Omega-3 fatty acids (fish oil) – Omega-3s have anti-inflammatory and neuroprotective effects and support heart and brain health. They may help with general inflammation and mood in chronic nerve disease. Supplements are usually taken with food and can cause fishy aftertaste or mild stomach upset. High doses may affect bleeding, so doctors should review all medicines first.PMC+1
Vitamin D – Vitamin D is vital for bone strength and muscle function. Many people with long-term disabilities have low levels because they are less active outdoors. Correcting deficiency with tablets or drops can reduce fracture risk and may improve muscle weakness slightly. Blood tests help guide safe dosing and avoid toxicity.PMC+1
Vitamin B12 (methylcobalamin) – B12 is essential for myelin and nerve health. If blood tests show low B12, replacement by tablets or injections can prevent further nerve damage and may improve sensation. It is generally safe, but high doses are not useful if levels are already normal, so testing is important before long-term use.PMC+1
Folate (vitamin B9) – Folate supports DNA synthesis and nerve repair. Low levels can worsen anemia and fatigue. Supplementation is useful when deficiency is confirmed or when certain medicines lower folate. It is usually taken once daily with food. People planning pregnancy should discuss appropriate doses with their doctor.Dove Medical Press+1
Coenzyme Q10 – CoQ10 supports mitochondrial energy production and acts as an antioxidant. Some small studies in neuromuscular disorders suggest it may improve fatigue or exercise tolerance. It is taken as an oral supplement with fat-containing meals. Possible side effects include stomach upset; interactions with blood thinners must be checked.PMC+1
Magnesium – Magnesium is important for muscle relaxation, nerve conduction, and sleep. Supplements may help cramps or restless legs in some people. They are usually taken at night and can cause loose stools if the dose is high. Blood tests may be needed if kidney function is reduced.PMC+1
N-acetylcysteine (NAC) – NAC is an antioxidant and glutathione precursor that may help protect cells from oxidative stress. It is used in other conditions but has limited direct evidence in CMT. It is usually taken orally, and side effects may include nausea and stomach discomfort. Use should be guided by a clinician who knows your full medical history.PMC+1
Probiotics – Gut health can influence inflammation, immunity, and mood. Probiotic supplements may help some people with digestive issues or antibiotic-related diarrhea. They do not treat the neuropathy itself but support general health, which indirectly helps with energy and resilience. Strain and dose choices should be discussed with a clinician or dietitian.PMC+1
Regenerative / Stem-Cell / Immunity Booster Drugs
At present, there are no approved stem-cell drugs or immunity booster medicines that specifically treat Charcot-Marie-Tooth disease axonal type 2C. Research is ongoing, and most approaches are still in early laboratory or trial stages. It is very important to avoid unregulated “stem cell clinics” that offer expensive treatments without strong evidence or safety data.PMC+2ResearchGate+2
TRPV4 inhibitors (e.g., ABS-0871 in trials) – ABS-0871 is an experimental drug that blocks the overactive TRPV4 channel believed to drive nerve damage in CMT2C. Laboratory data suggest that blocking TRPV4 may reduce toxic calcium influx and improve cell survival. A phase 1 clinical trial is testing safety and how the body handles the drug; it is not yet approved for general use.Actio Biosciences+2Actio Biosciences+2
Gene therapy approaches – Scientists are exploring gene silencing, gene editing, and gene replacement to correct or reduce harmful TRPV4 activity. Viral vectors or other delivery systems are tested first in cell and animal models. These techniques aim to target the root cause but still carry risks such as immune reactions and unwanted genetic changes, so they remain experimental.PMC+2ResearchGate+2
Neurotrophic factor–based therapies – Research is looking at molecules that stimulate nerve growth and repair, such as nerve growth factor analogs or other neurotrophic factors. The goal is to support damaged axons and Schwann cells, but results in clinical trials for CMT have been mixed, and no such therapy is approved yet.PMC+1
Mesenchymal stem-cell (MSC) therapies (experimental) – MSCs from bone marrow or fat tissue are studied in other neuropathies for their potential to release growth factors and modulate inflammation. For CMT2C, evidence is still mostly pre-clinical or from small early-phase studies. Any MSC treatment should only be received inside regulated clinical trials, not at commercial clinics.PMC+1
Immune-modulating drugs in overlapping conditions – CMT2C itself is not an autoimmune disease, but if a person has overlapping autoimmune neuropathy, physicians may use immunoglobulins, steroids, or other immunosuppressants. These medicines adjust immune activity and can help those specific disorders but do not correct the TRPV4 gene mutation.Dove Medical Press+1
Supportive “immune booster” strategies – Rather than special drugs, the best way to keep the immune system strong in CMT2C is through routine vaccinations, good sleep, nutrition, and exercise within safe limits. These lifestyle measures support the body’s natural defences against infection, which is important if breathing muscles are weak.Scientia Salut+1
Surgeries – Common Procedures and Why They Are Done
Foot and ankle tendon transfer surgery
In tendon transfer surgery, surgeons move working tendons to replace those that no longer function properly, often to correct foot drop or improve ankle stability. This can make the foot more level during walking, reduce tripping, and improve shoe fit. It is usually done after braces and therapy have been tried and when deformity is flexible enough to correct.ScienceDirect+1Foot deformity correction (osteotomy)
When the foot is very high-arched or twisted, surgeons may cut and realign bones (osteotomy) to create a more stable, plantigrade foot. This operation aims to distribute pressure more evenly, reduce pain, and make bracing and shoes more comfortable. Recovery involves casting and therapy to restore safe walking.ScienceDirect+1Joint fusion (arthrodesis)
In severe deformities with arthritis, surgeons may fuse joints in the foot or ankle to lock them in a better position. This sacrifices some movement but increases stability and reduces pain. Arthrodesis is usually considered after other operations fail or when joints are very damaged.ScienceDirect+1Spinal surgery for scoliosis or deformity
Some people with long-standing muscle weakness develop scoliosis or spinal deformity that affects posture or breathing. In such cases, spinal fusion or deformity correction may be considered. The goal is to improve balance, relieve pain, and protect lung function. These are major procedures and require evaluation by a spine surgeon experienced in neuromuscular conditions.Dove Medical Press+1Vocal cord or airway surgery
Because vocal cord paresis is common in CMT2C, ENT surgeons may perform procedures such as vocal cord medialization or other airway surgeries to improve voice strength or breathing. These operations aim to reduce hoarseness, prevent aspiration, and support safer breathing, especially at night. Decisions are based on detailed voice and airway assessments.Charcot-Marie-Tooth Disease+1
Practical Preventions and Protective Strategies
Even though CMT2C cannot be fully prevented, many complications can be reduced:
Avoid known neurotoxic medicines (for example, some chemotherapy or high-dose vitamin B6) whenever safer alternatives exist; always tell doctors you have CMT.Scientia Salut+1
Keep a healthy body weight to reduce stress on weak feet, ankles, and knees.
Follow regular physical and occupational therapy programs to maintain strength, flexibility, and balance.MDPI+1
Use braces, footwear, and walking aids early rather than waiting for serious falls.ScienceDirect+1
Check feet daily for blisters, cuts, or redness, especially if sensation is reduced.Scientia Salut+1
Keep vaccinations up to date, including flu and pneumonia vaccines, to reduce chest infection risks when breathing muscles are weak.Scientia Salut+1
Do home safety checks to remove tripping hazards and improve lighting.
Manage other health conditions, such as diabetes or thyroid disease, which can worsen nerve damage.PMC+1
Seek psychological support early for anxiety or depression, rather than waiting until crisis.PMC+1
Use genetic counseling before pregnancy to understand recurrence risks and options.National Organization for Rare Disorders+1
When to See a Doctor Urgently or for Review
People with Charcot-Marie-Tooth disease axonal type 2C should have regular follow-up with a neurologist and rehabilitation team. You should seek urgent medical advice if you notice rapidly worsening weakness, new severe breathing problems, chest pain, sudden voice changes that affect breathing, or trouble swallowing and choking. These may signal new complications such as respiratory failure, serious infections, or other conditions that need prompt treatment.Charcot-Marie-Tooth Association+2Scientia Salut+2
You should also book a review if braces no longer fit, you develop new foot ulcers, pain suddenly changes or becomes unbearable, mood or sleep problems start to dominate your days, or you are planning surgery, pregnancy, or a major life change. Regular assessments allow early adjustments of therapy, equipment, and medicines to keep you as independent and safe as possible.Dove Medical Press+1
What to Eat and What to Avoid
Focus on a balanced diet rich in whole grains, fruits, vegetables, lean protein, and healthy fats to support overall energy and muscle health.PMC+1
Include sources of omega-3 fats (such as fish, walnuts, and flaxseed) several times per week to support heart and brain health.PMC+1
Ensure adequate calcium and vitamin D from foods like dairy, fortified plant milks, and leafy greens to protect bones if mobility is limited.PMC+1
Eat enough protein from beans, lentils, eggs, dairy, fish, or lean meat to support muscle maintenance and repair.
Drink enough water to stay hydrated, which helps prevent constipation and supports overall well-being.
Avoid heavy alcohol use, which can worsen nerve damage and interact with many medicines.PMC+1
Limit sugary drinks and highly processed snacks, which add calories without nutrients and may worsen weight gain and fatigue.
Avoid very high doses of vitamin B6 supplements unless specifically prescribed, as excess B6 can itself cause neuropathy.Scientia Salut+1
Be cautious with fad “nerve cure” diets or untested supplements promoted online; discuss any major diet change with your doctor or dietitian.
If chewing or swallowing is difficult due to vocal cord or throat weakness, see a speech therapist and dietitian to adjust food textures and prevent choking and weight loss.Charcot-Marie-Tooth Disease+1
Frequently Asked Questions (FAQs)
Is Charcot-Marie-Tooth disease axonal type 2C curable?
No. At present there is no cure for CMT2C and no medicine that can fully stop or reverse the nerve damage. Treatment aims to manage symptoms, maintain mobility, and prevent complications. Research on TRPV4 inhibitors and gene therapies is ongoing but still experimental.PMC+2ResearchGate+2How is CMT2C different from other types of CMT?
CMT2C is an axonal form linked to TRPV4 mutations and is especially known for affecting vocal cords, diaphragm, and sometimes hearing, in addition to limb weakness and sensory loss. Other CMT types may mainly affect myelin or have different patterns of weakness and associated features.PubMed+2Charcot-Marie-Tooth Disease+2At what age do symptoms usually start?
Symptoms can start in infancy, childhood, or early adult life. Some people first notice frequent tripping and high-arched feet as children, while others present later with hand weakness, hoarseness, or breathing issues. The severity and speed of progression vary widely, even within the same family.National Organization for Rare Disorders+2Charcot-Marie-Tooth Disease+2Can exercise make my CMT2C worse?
Well-planned, moderate exercise under physiotherapy guidance usually helps, not harms. Over-exertion and heavy strength training that causes prolonged muscle pain should be avoided. Exercise should be tailored to your current strength and fatigue levels and adjusted over time.PMC+2MDPI+2Will I need a wheelchair?
Some people with CMT2C use wheelchairs or scooters part-time or full-time, especially for longer distances. Using a wheelchair can protect energy and prevent falls, allowing more participation in school, work, and social life. The decision depends on individual strength, balance, and goals.PMC+2Dove Medical Press+2Can CMT2C affect breathing and sleep?
Yes. Diaphragm and vocal cord weakness can cause shortness of breath, especially when lying flat, and disturbed sleep with morning headaches or daytime sleepiness. Respiratory tests and sleep studies help detect problems early, and non-invasive ventilation can greatly improve symptoms and safety.Charcot-Marie-Tooth Association+1Is pregnancy safe if I have CMT2C?
Many people with CMT have successful pregnancies, but extra planning is needed. Weakness, breathing function, and spinal deformity must be assessed, and anesthesia plans carefully made. Genetic counseling can help explain inheritance patterns and options. A high-risk obstetric team and neurologist should be involved.National Organization for Rare Disorders+2Scientia Salut+2Can children with CMT2C play sports?
Many children can participate in adapted sports and physical activity, which are important for fitness and social life. Low-impact activities such as swimming or cycling are usually safer. Coaches and teachers should understand the condition and allow rest breaks and equipment such as braces.MDPI+2The Physio Lab+2Will my symptoms always get worse?
CMT2C is typically slowly progressive, but the rate of change varies. Some people remain quite stable for long periods, especially with good therapy, while others decline more quickly. Regular follow-up allows early adjustments in treatment to maintain function for as long as possible.PMC+2Scientia Salut+2Should my family members be tested?
Genetic testing of relatives is a personal choice. It can clarify who is at risk and assist with family planning, but it may also bring emotional stress. Genetic counselors help families weigh pros and cons and decide when and how to test.National Organization for Rare Disorders+1Are there special anesthetic risks in CMT2C?
Yes. Anesthetists need to know about CMT2C, breathing function, and any spine or vocal cord problems before surgery. Some muscle relaxants and positioning choices must be considered carefully. A pre-operative anesthetic assessment is important for safety.Scientia Salut+1Can diet change my disease?
No specific diet can cure or directly slow CMT2C, but a healthy diet supports weight control, bone strength, and general health, which all affect mobility and energy. Avoiding alcohol misuse and vitamin B6 excess can protect nerves from extra harm.PMC+2Dove Medical Press+2Is CMT2C common?
CMT as a whole is one of the most common inherited nerve diseases, but CMT2C specifically is rare. Many clinicians may never see a case, which is why referral to centres with neuromuscular expertise and access to genetic testing is helpful.PMC+2PubMed+2Where can I find reliable information and support?
Trusted sources include national neuromuscular disease associations and CMT foundations, which provide educational materials, updates on research, and peer support networks. They can also help you find specialists, therapists, and clinical trial opportunities for CMT2C.Actio Biosciences+2Charcot-Marie-Tooth Association+2What is the most important thing I can do today?
The most important step is to build a long-term partnership with a knowledgeable care team, stay active within safe limits, protect your feet and balance, and look after your mental health. Small, consistent actions in therapy, lifestyle, and follow-up visits add up over time and can significantly improve quality of life with Charcot-Marie-Tooth disease axonal type 2C.PMC+2Dove Medical Press+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.
