Autosomal Dominant Axonal Charcot-Marie-Tooth Disease Type 2Z (CMT2Z)

Autosomal dominant axonal Charcot-Marie-Tooth disease type 2Z (CMT2Z) is a rare hereditary nerve disease caused by harmful changes in the MORC2 gene. It mainly damages the long peripheral nerves that carry signals to and from the legs and arms. People often have weakness and wasting of muscles in the feet and lower legs, balance problems, high-arched or very flat feet, and reduced feeling in the toes and fingers. In some families it starts in childhood, in others later in life. It is progressive, meaning symptoms usually slowly get worse over many years. There is no cure yet, but many treatments can reduce symptoms, protect function, and improve quality of life. Orpha+2nature.com+2

Autosomal dominant axonal Charcot-Marie-Tooth disease type 2Z (often shortened to CMT2Z) is a rare inherited nerve disease. It mainly damages the axons (the long parts) of peripheral nerves, which carry signals between the spinal cord and the muscles and skin. People with this condition slowly develop weakness and thinning of muscles in the feet, legs, hands, and sometimes other parts of the body. Many also have numbness or reduced feeling in the feet and hands. The disease is called autosomal dominant because only one changed copy of the gene is enough to cause it, and a parent with the disease has a 50% chance to pass it to each child.NCBI+1

Most cases of CMT2Z are caused by a change (mutation) in a gene called MORC2, which sits on chromosome 22. This gene helps control how DNA is packed and how genes are switched on and off in nerve cells. When MORC2 is faulty, long nerves in the legs and arms cannot keep their structure and function, so they slowly degenerate. Symptoms often start in childhood or teenage years, but sometimes earlier in infancy or later in adult life.NCBI+1

---

Another names

This condition has several other names in medical books and databases. These names all describe the same disease or very closely related forms:

• Charcot-Marie-Tooth disease axonal type 2Z – this highlights that the problem is mainly in the axon part of the nerve and that it belongs to the CMT2 group.malacards.org

• CMT2Z – short and commonly used name in clinics and research.NCBI

• Charcot-Marie-Tooth neuropathy type 2Z – “neuropathy” means nerve disease; this name is often used in genetic and neurology databases.NCBI+1

• Autosomal dominant Charcot-Marie-Tooth disease type 2Z – this adds the inheritance pattern “autosomal dominant”.NCBI

• Charcot-Marie-Tooth disease, axonal, autosomal dominant, type 2Z – a longer synonym used in MedGen and OMIM.NCBI+1

• MORC2-related axonal Charcot-Marie-Tooth disease – this name stresses the genetic cause in the MORC2 gene.Frontiers+1

All of these names describe the same core disorder: a slowly progressive, inherited axonal neuropathy due to MORC2 variants.

---

Types

Doctors usually think of CMT2Z as one genetic disease, but people can show different clinical patterns. These patterns are sometimes called “types” or “phenotypes”. They depend on the exact MORC2 mutation and on the individual person.NCBI+2nature.com+2

• 1. Classic childhood-onset CMT2Z
  In this pattern, symptoms start in childhood or the teenage years. The first signs are often weakness in the feet and lower legs, frequent tripping, difficulty running, and high-arched feet. Over time, weakness and wasting spread upwards and may involve the hands, but progression is usually slow over many years.NCBI+1

• 2. Infantile-onset hypotonic pattern
  Some babies with MORC2 changes show early hypotonia (low muscle tone) and generalized weakness. They may be late to hold up the head, sit, or walk. Later they can develop typical CMT features such as distal weakness, sensory loss, and foot deformities. This pattern overlaps with other early-onset motor neuron or neuropathy syndromes.NCBI+1

• 3. CMT2Z with pyramidal signs
  In some patients, there are extra signs that the pyramidal tracts (motor pathways in the brain and spinal cord) are involved. These people may have increased muscle tone (spasticity), brisk reflexes, or an extensor plantar (Babinski) response. This combination of peripheral neuropathy plus pyramidal signs is well described in MORC2-related disease.NCBI+2malacards.org+2

• 4. Overlap with neurodevelopmental syndromes (DIGFAN / SMA-like)
  Certain MORC2 variants can cause a broader syndrome with developmental delay, impaired growth, facial differences, and axonal neuropathy, sometimes called DIGFAN. Some patients show a picture between classic CMT2Z and these more complex syndromes, with features of both. This shows that MORC2 changes form a spectrum rather than completely separate diseases.nature.com+2Frontiers+2

These clinical “types” are useful for describing patients, but genetically they are all linked to changes in the same MORC2 gene.

---

Causes of autosomal dominant axonal CMT type 2Z

For this disease, the main cause is always a harmful change in the MORC2 gene. There are not 20 different unrelated causes, but there are different ways and conditions in which this genetic cause appears or is modified.

1. Pathogenic MORC2 point mutation (main cause)
The primary cause is a pathogenic variant (mutation) in the MORC2 gene. A single changed base in the DNA can alter the MORC2 protein so that it cannot work normally in nerve cells. This leads to damage of long peripheral nerves and causes the typical CMT2Z picture.NCBI+2malacards.org+2

2. Autosomal dominant inheritance from an affected parent
Many patients inherit the mutation from a parent who also has CMT2Z. Because the disease is autosomal dominant, each child of an affected parent has a 50% chance to inherit the mutant gene and therefore the disease.NCBI+1

3. De novo MORC2 mutation
In some cases, the MORC2 mutation is de novo, meaning it appears for the first time in the child and is not found in either parent. This happens when a copying error occurs in egg or sperm cells, or very early in embryo development. These de novo cases explain children with CMT2Z born to healthy parents.Frontiers+1

4. Missense variants affecting the ATPase module of MORC2
Research shows that many disease-causing changes in MORC2 cluster in domains that act like an ATPase “engine” inside the protein. When this engine is altered, the protein cannot control DNA structure and gene expression in nerve cells properly. This abnormal control contributes to axonal degeneration.nature.com+1

5. Gain-of-function mechanism
Some MORC2 mutations are thought to be gain-of-function changes. This means they make the protein too active or give it a new harmful activity, rather than simply switching it off. Overactive MORC2 can disturb chromatin and gene regulation, harming neuronal survival.Wiley Online Library+1

6. Toxic effect on axonal maintenance
Axons of long nerves need constant support to keep their structure and to transport materials. Faulty MORC2 disrupts this support system in peripheral neurons, causing progressive axonal degeneration, especially in the longest nerves to the feet and hands.malacards.org+1

7. Disruption of DNA repair and chromatin remodeling
MORC2 is involved in managing how DNA is packed (chromatin) and how cells respond to DNA damage. Mutations can interfere with these processes, leading to chronic stress in nerve cells and gradual nerve fiber loss.Wiley Online Library+1

8. Mitochondrial and oxidative stress in nerve cells
Experimental models suggest that altered MORC2 can increase oxidative stress and disturb energy handling inside neurons. This makes axons more fragile and easier to damage over time, especially under metabolic or environmental stress.malacards.org+1

9. Genetic background and modifier genes
People with the same MORC2 mutation can have different severity. This suggests that other genes (“modifier genes”) in a person’s genome can make the neuropathy milder or more severe, although these modifiers are not fully known yet.NCBI+1

10. Epigenetic influences
Because MORC2 regulates chromatin, changes in epigenetic marks (such as DNA methylation and histone modifications) might interact with MORC2 mutations. This may change which genes are turned on or off in neurons and thus shape how strongly the disease shows.Wiley Online Library

11. Early developmental effects on the nervous system
Some patients show developmental delay, short stature, or facial differences. This suggests that MORC2 mutations can disturb brain and body development as well as peripheral nerves, especially when the mutation acts very early in life.NCBI+2nature.com+2

12. Disease onset during periods of growth
Symptoms often appear during childhood or early adulthood, when nerves are under stress from rapid growth and increased activity. Growth periods may reveal the underlying weakness caused by the MORC2 mutation.Lippincott Journals+1

13. Mechanical stress on long nerves
Long nerves to the feet and hands are more vulnerable to any inherited axonal problem. Daily mechanical stress, such as walking and standing, can worsen axonal damage in nerves already weakened by MORC2 mutations.CMT Research Foundation

14. Co-existing health conditions
Other illnesses, such as diabetes, vitamin deficiencies, or thyroid disease, do not cause CMT2Z but can add extra nerve damage in someone who already has MORC2-related neuropathy, making symptoms worse or appear earlier.CMT Research Foundation

15. Lifestyle factors (for example, neurotoxic alcohol use)
Heavy alcohol use or poor nutrition can damage nerves in general. In a person with CMT2Z, such factors can add to the genetic damage, causing quicker progression or more severe symptoms, although they are not primary causes.CMT Research Foundation

16. Exposure to neurotoxic medications
Certain chemotherapy drugs and other neurotoxic medicines can harm peripheral nerves. If a person with a MORC2 mutation receives these drugs, they may experience greater neuropathy than a person without such a mutation.CMT Research Foundation

17. Repeated minor injuries or poor footwear
Long-standing pressure, bad footwear, or repeated ankle sprains do not cause CMT2Z, but they can worsen deformities and symptoms in feet and ankles already weakened by the disease.CMT Research Foundation

18. Aging of the nervous system
As people age, nerves naturally lose some function. In CMT2Z, this normal age-related decline adds to the inherited axonal problem, so symptoms often gradually progress over decades.CMT Research Foundation

19. Reduced nerve repair capacity
Damaged peripheral nerves can sometimes repair themselves. However, MORC2-related changes may limit this repair capacity, so small injuries accumulate instead of healing fully.malacards.org+1

20. Family-specific or variant-specific effects
Different MORC2 variants can cause slightly different disease patterns and severity. Some families may have more pyramidal signs, others more developmental problems. These variant-specific effects are an important cause of the wide clinical spectrum seen in CMT2Z.NCBI+2nature.com+2

---

Symptoms and signs of autosomal dominant axonal CMT type 2Z

Symptoms of CMT2Z are usually slowly progressive and often start in the legs. Many reflect damage to motor nerves (weakness and wasting) and sensory nerves (numbness and loss of feeling).

1. Distal lower-limb muscle weakness
The most common early sign is weakness in the muscles of the feet and ankles. People may have trouble running, climbing stairs, or standing on their toes. This is due to loss of motor axons supplying the distal leg muscles.NCBI+1

2. Distal muscle wasting (amyotrophy)
Over time, the small muscles in the lower legs and feet become visibly thinner. The lower legs can look like an “inverted champagne bottle”. This muscle wasting reflects long-standing axonal loss in motor nerves.NCBI

3. Difficulty walking and gait disturbance
People often develop an abnormal gait. They may trip easily, drag their feet, or need to lift the knees high to clear the toes (“steppage gait”). Balance problems may also appear as the disease progresses.NCBI+1

4. Foot deformities (such as pes cavus or hammer toes)
High-arched feet (pes cavus), clawed or hammer toes, and other foot deformities are frequent. They develop because weak muscles cannot balance the stronger ones, and bones slowly change shape under altered forces.NCBI+1

5. Distal sensory loss (numbness and reduced feeling)
Many patients notice numbness, tingling, or reduced feeling in the feet and later in the hands. They may not feel pain, temperature, or vibration well. This happens because sensory axons are damaged.NCBI+1

6. Loss or reduction of tendon reflexes (hyporeflexia/areflexia)
Doctors often find that ankle reflexes and sometimes knee reflexes are reduced or absent. This is because the reflex arc depends on healthy motor and sensory fibers, which are damaged in CMT2Z.NCBI

7. Muscle cramps and spasms
Some patients experience painful muscle cramps, especially in the calves and feet. These result from unstable or irritated motor units in partially damaged nerves.NCBI+1

8. Hand weakness and loss of fine motor skills
As the disease spreads to upper limbs, people may have trouble with buttons, writing, or holding small objects. Intrinsic hand muscles may become weak and wasted, making tasks that need fine motor control difficult.NCBI+1

9. Balance problems and gait ataxia
Damage to sensory fibers that carry joint position and vibration sense can cause sensory ataxia. Patients may feel unsteady, especially in the dark or with eyes closed, because they cannot sense where their feet are.NCBI+1

10. Fatigue and reduced stamina
Chronic weakness and nerve damage often cause significant tiredness. People may feel exhausted after walking short distances or doing simple tasks, because their muscles must work harder and compensation from other muscles is needed.

11. Pyramidal signs (spasticity, Babinski sign) in some patients
In certain individuals, examination shows increased muscle tone, brisk reflexes, or an upgoing plantar response (Babinski sign). These pyramidal signs suggest that MORC2-related disease can affect central motor pathways as well as peripheral nerves.NCBI+2malacards.org+2

12. Scoliosis and posture changes
Weak trunk and paraspinal muscles, together with imbalance in muscle pull, can lead to scoliosis (curved spine) or other posture changes. These may progress during growth and may need orthopedic monitoring.NCBI

13. Hypotonia or hypertonia (low or high muscle tone)
In early-onset cases, babies may have hypotonia (floppy muscles). In other patients with pyramidal involvement, there may be hypertonia (stiff muscles). Both reflect different kinds of nerve pathway involvement in MORC2-related disease.NCBI+1

14. Learning difficulties or developmental delay in some cases
A small number of patients with MORC2 mutations show global developmental delay, learning problems, or other neurodevelopmental features, especially in the broader DIGFAN spectrum. This suggests effects on the brain as well as on peripheral nerves.NCBI+2nature.com+2

15. Hearing loss or voice changes (rare features)
In some reported patients, there is hearing impairment or an abnormally high-pitched voice. These features are not typical for every case but can appear in the extended MORC2 phenotype.NCBI+1

---

Diagnostic tests for autosomal dominant axonal CMT type 2Z

Diagnosis of CMT2Z is based on history, examination, nerve tests, and genetic testing. The goal is to show that there is an axonal neuropathy and then find the exact MORC2 mutation.

Physical examination tests (bedside assessment)

1. Comprehensive neurological examination
The neurologist checks muscle strength, tone, reflexes, and coordination in all limbs. In CMT2Z, this exam usually shows distal weakness, muscle wasting, reduced or absent tendon reflexes, and sometimes pyramidal signs. It helps confirm that there is a mixed motor and sensory neuropathy.NCBI+1

2. Gait and posture assessment
The doctor observes how the person walks, stands, and turns. Features such as steppage gait, foot drop, or unsteady, wide-based walking suggest distal weakness and impaired sensory feedback. This simple observation is very helpful for spotting CMT-like patterns.NCBI+1

3. Foot and ankle examination
Clinicians carefully look at the shape of the feet and ankles for signs like pes cavus, hammer toes, and ankle instability. They also check skin, calluses, and pressure areas. These findings support long-standing neuropathy and guide orthotic or surgical planning.NCBI+1

4. Spine and skeletal examination
The spine is checked for scoliosis or abnormal curves, and the hips and knees are examined for contractures. Detecting these problems early allows referral to orthopedic specialists for bracing or other treatments to maintain function.NCBI+1

Manual tests (bedside functional maneuvers)

5. Manual muscle testing (MRC scale)
The examiner tests individual muscle groups (for example ankle dorsiflexion, plantarflexion, finger abduction) using their hands and grades strength on the Medical Research Council (MRC) scale from 0 to 5. This shows which muscles are weak and tracks progress over time.NCBI+1

6. Sensory testing for touch, pain, and temperature
Using simple tools like cotton wool, a pin, or a cool metal object, the doctor checks light touch, pinprick, and temperature sensation. Reduced or absent responses in a “stocking-glove” pattern support the diagnosis of length-dependent sensory neuropathy.NCBI

7. Vibration and joint position sense testing
A tuning fork is placed on bony points at the toes and ankles to test vibration sense, and toes are gently moved up and down to test joint position sense. In CMT2Z, these senses are often impaired distally. This explains balance problems and unsteady gait.NCBI+1

8. Balance and coordination tests (e.g., Romberg, tandem gait)
In the Romberg test, the patient stands with feet together and eyes closed; in tandem gait, they walk heel-to-toe. Increased sway or loss of balance suggests impaired proprioception and supports sensory involvement in the neuropathy.NCBI+1

Laboratory and pathological tests

9. Targeted MORC2 genetic testing
The most important laboratory test is DNA testing for mutations in MORC2. This is usually done from a blood sample. Finding a known pathogenic variant confirms the diagnosis of CMT2Z and allows testing of relatives.NCBI+2malacards.org+2

10. Comprehensive CMT or neuropathy gene panel
Because many genes can cause hereditary neuropathies, clinicians often order a multi-gene panel that includes MORC2 and other CMT genes. This approach is efficient and can detect unexpected genetic causes or additional variants.malacards.org+1

11. Exclusion blood tests (metabolic and acquired causes)
Blood tests such as fasting glucose, vitamin B12, thyroid function, kidney and liver function are done to rule out acquired neuropathy causes (like diabetes or vitamin deficiency). In pure CMT2Z, these tests are usually normal, but they help ensure no additional treatable cause is present.CMT Research Foundation

12. Nerve biopsy (rarely needed now)
In special cases, a small piece of nerve (often the sural nerve near the ankle) may be taken for biopsy. Under the microscope, CMT2Z shows axonal loss rather than demyelination. Today, genetic tests often replace biopsy, so it is reserved for unclear or research cases.malacards.org+1

Electrodiagnostic tests

13. Motor nerve conduction studies (NCS)
Electrodes are placed on the skin to stimulate motor nerves and record the response from muscles. In CMT2Z, conduction velocities are usually normal or only mildly reduced, but the response amplitudes are decreased, which is typical of axonal neuropathy. This helps distinguish CMT2 from demyelinating CMT1.NCBI+2malacards.org+2

14. Sensory nerve conduction studies
Similar tests are done on sensory nerves, such as the sural nerve in the leg. In CMT2Z, amplitudes of sensory nerve action potentials are often reduced, consistent with loss of sensory axons. Together with clinical findings, this supports a diagnosis of length-dependent sensory neuropathy.NCBI+1

15. Electromyography (needle EMG)
A fine needle electrode is inserted into selected muscles to record electrical activity at rest and during contraction. In CMT2Z, EMG often shows signs of chronic denervation and re-innervation, such as large motor units and reduced recruitment. This confirms that muscles are affected secondary to nerve damage.malacards.org+1

16. Somatosensory evoked potentials (SSEPs) in selected cases
In patients with pyramidal signs or suspected central involvement, doctors may use SSEPs, which measure the brain’s response to nerve stimulation. Abnormal SSEPs can show whether central pathways are involved in addition to the peripheral neuropathy.NCBI+1

Imaging tests

17. MRI of brain and spinal cord (if central signs or developmental features)
Magnetic resonance imaging (MRI) of the brain and spinal cord can help rule out other diseases and look for central nervous system involvement. In some MORC2-related cases, MRI may show subtle changes, especially when there is developmental delay or pyramidal signs.nature.com+1

18. Muscle MRI
MRI of leg and thigh muscles can show patterns of fatty replacement and atrophy typical of hereditary neuropathies. Different muscles are affected to different degrees, and these patterns can help characterize disease severity and progression.CMT Research Foundation

19. X-rays of feet, ankles, and spine
Plain radiographs (X-rays) of the feet and ankles reveal bone changes due to long-standing deformities, such as high arches and toe contractures. Spinal X-rays can show scoliosis or other alignment problems. Orthopedic surgeons use these images for planning braces or surgery.NCBI+1

20. Nerve ultrasound (high-resolution peripheral nerve imaging)
In some centers, ultrasound is used to look at peripheral nerves. In axonal CMT, nerves may show mild or no enlargement compared with demyelinating forms. Although still mainly a research tool, nerve ultrasound can give extra structural information in inherited neuropathies.CMT Research Foundation

---

Non-pharmacological treatments

1. Individualized physiotherapy program
   A structured physiotherapy program is one of the most important non-drug treatments for CMT2Z. The therapist designs exercises to keep joints moving, protect muscles from further weakness, and improve walking, balance, and stamina. Gentle strengthening, stretching, and balance work are planned according to the person’s current strength and fatigue level. The purpose is to maintain independence in walking and daily activities for as long as possible. The main mechanism is simple: repeated, safe movement helps preserve remaining muscle fibers, keeps joints flexible, and teaches the nervous system to use remaining pathways more efficiently. MDPI+2Physiopedia+2

2. Strength training for weak muscles
   Targeted strengthening focuses on muscles that are still able to work but are weaker than normal, especially around the ankles, knees, and hips. Low-resistance, high-repetition exercises (such as theraband work or light weights) are usually safer than heavy lifting. The purpose is to slow loss of strength, improve push-off during walking, and make stairs and transfers easier. The mechanism is normal muscle adaptation: repeated effort causes surviving muscle fibers to become thicker and more efficient, so they can partly compensate for fibers already lost from nerve damage. MDPI+1

3. Stretching and contracture prevention
   Because weak muscles are easily overpowered by tighter muscles and gravity, joints may slowly become fixed in bent positions. Daily stretching of ankles, calves, hamstrings, and toes helps prevent contractures. The purpose is to keep a neutral or plantigrade foot position so shoes fit better and walking is safer. The mechanism is mechanical: slow, repeated stretching of tendons, muscles, and joint capsules keeps them longer and more flexible, reducing the tendency for the foot to curl into a cavovarus or equinus deformity. Physiopedia+1

4. Balance and gait training
   Many people with CMT2Z have poor balance because of weak ankles and reduced sensation in the feet. Balance training uses simple tasks such as standing with feet close together, stepping over objects, and walking on different surfaces in a controlled setting. The purpose is to reduce falls and build confidence in walking. The mechanism is neuroplasticity: repeated practice teaches the brain to use visual and inner-ear (vestibular) signals more effectively and to coordinate remaining muscle power to keep the body stable. MDPI+1

5. Aerobic endurance training
   Gentle aerobic exercise such as stationary cycling, pool walking, or brisk walking within safe limits can improve heart and lung fitness. The purpose is to reduce fatigue, support a healthy weight, and improve overall energy, which often helps people stay more active in daily life. The mechanism is increased efficiency of the cardiovascular system and mitochondria (the cell’s power plants), so muscles get more oxygen and can work longer before tiring, even when they are partially denervated. PMC+1

6. Ankle-foot orthoses (AFOs)
   Lightweight braces for the ankles and feet are commonly used in CMT type 2. They help control foot drop, stabilize weak ankles, and improve toe clearance during walking. The purpose is safer, more energy-efficient walking with fewer trips and falls. The mechanism is mechanical and supportive: the brace holds the ankle in a neutral position, stores some energy during step-off, and guides the foot so that the heel strikes the ground first instead of the toes. PMC+1

7. Custom footwear and insoles
   Special shoes with a wide toe box, firm heel counter, and cushioned soles, plus custom insoles, can redistribute pressure under the feet. This is important when there are high arches, hammertoes, or calluses. The purpose is to reduce pain, prevent skin breakdown, and improve stability. The mechanism is pressure redistribution: soft materials and shaped inserts spread weight more evenly, reducing stress on bony prominences and improving contact between the foot and the ground. nmd-journal.com+1

8. Hand and wrist splints
   Some people with CMT2Z develop weakness and wasting in the hands, making grip and fine tasks difficult. Night splints or functional hand braces can support the wrist in a useful position and reduce fatigue while writing, typing, or cooking. The purpose is to maintain independence with self-care and work tasks. The mechanism is external stabilization: the splint substitutes for weak muscles so that remaining stronger muscles can focus on precise finger movements. NCBI+1

9. Occupational therapy and energy conservation
   Occupational therapists help people adapt daily routines, tools, and home layouts to match their abilities. They teach “energy conservation” strategies such as pacing activities, sitting for tasks instead of standing, and planning rest breaks. The purpose is to reduce fatigue and maintain productivity at home, school, or work. The mechanism is practical: by modifying tasks and using assistive devices, the person spends less energy on basic chores, leaving more capacity for important activities and participation. Charcot-Marie-Tooth Association+1

10. Assistive devices for mobility
    Canes, trekking poles, walkers, or wheelchairs may be recommended when balance or leg strength is very limited. These devices are not a “failure”; they are tools that allow people to move farther and more safely. The purpose is to prevent falls and maintain access to community activities. The mechanism is additional points of support and weight distribution, which reduce the load on weak muscles and improve stability during standing and walking. SAGE Journals+1

11. Pain psychology and cognitive-behavioural therapy (CBT)
    Chronic neuropathic pain and disability can affect mood, sleep, and coping. Psychological therapies such as CBT help people understand the pain, change unhelpful thoughts, and build coping strategies. The purpose is to reduce the emotional burden of pain and improve quality of life, even when pain cannot be fully removed. The mechanism is central: changing thoughts and behaviours can reduce stress-driven pain amplification in the brain and make symptoms feel more manageable. PMC

12. Fatigue management and sleep hygiene
    Many people with CMT report significant fatigue. Structured fatigue programs focus on regular sleep schedules, smart rest breaks, and avoiding “boom-and-bust” activity patterns. The purpose is to stabilize energy across the day and avoid crashes that worsen pain and weakness. The mechanism is better regulation of circadian rhythms and more even use of physical and mental effort, which reduces stress on already vulnerable nerves and muscles. Charcot-Marie-Tooth Association+1

13. Home safety and fall-prevention modifications
    Simple changes at home – such as removing loose rugs, adding grab bars, improving lighting, and using non-slip mats – can greatly reduce falls. The purpose is to protect against fractures, head injury, and loss of confidence after repeated falls. The mechanism is environmental: when the walking surface is safer, a person with weak feet and poor sensation faces fewer unexpected challenges that might cause a fall. Charcot-Marie-Tooth Association+1

14. Genetic counselling for family planning
    Because CMT2Z is autosomal dominant, a parent with the MORC2 variant has a 50% chance of passing it to each child. Genetic counselling gives families clear information about inheritance, testing options, and reproductive choices. The purpose is informed planning and emotional support. The mechanism is educational and supportive: understanding risk reduces fear and helps families make decisions that fit their values and life goals. Orpha+1

15. Patient education and self-management coaching
    Detailed education about CMT2Z, expected progression, and realistic goals helps people feel more in control. Learning how to pace activities, protect joints, and recognize warning signs turns them into active partners in care. The purpose is long-term self-management rather than crisis-based care. The mechanism is empowerment: informed patients are more likely to follow safe exercise, use braces correctly, and seek help early when new problems appear. PMC+1

16. Vocational rehabilitation and workplace adjustments
    For students and working adults, nerve weakness can interfere with job tasks. Vocational rehab specialists help adapt the workplace, recommend ergonomic tools, and, if needed, guide career changes. The purpose is to maintain employment and financial independence. The mechanism is environmental and social: matching the physical demands of work to the person’s abilities reduces overuse injuries and stress while keeping them engaged and productive. SAGE Journals

17. Hydrotherapy and pool-based exercise
    Exercising in warm water can be very helpful when land-based exercise is painful or tiring. Water supports body weight and allows smoother, slower movements. The purpose is to strengthen muscles and improve flexibility with less joint stress. The mechanism is buoyancy and resistance: water lightens the load on joints while still providing enough resistance to stimulate muscles safely. MDPI+1

18. Orthopaedic monitoring of foot deformities
    Regular review by an orthopaedic or foot and ankle specialist allows early detection of cavovarus foot, hammertoes, or severe flat feet. Early bracing or minor procedures can sometimes prevent more serious deformity later. The purpose is to keep the foot as plantigrade and functional as possible. The mechanism is early mechanical correction of muscle imbalance and joint alignment before permanent bony changes occur. PubMed+1

19. Support groups and peer networks
    Connecting with other people living with CMT can reduce isolation, share practical tips, and offer emotional support. Online communities and patient organizations often provide educational materials and advocacy. The purpose is psychological well-being and empowerment. The mechanism is social: feeling understood and supported reduces anxiety and depression and can motivate people to stay active in their own care plans. Charcot-Marie-Tooth Association

20. Regular multidisciplinary follow-up
    Because CMT2Z affects many aspects of life, care is best given by a team: neurologist, physiotherapist, occupational therapist, orthopaedic surgeon, genetic counsellor, and sometimes pain or rehabilitation specialists. The purpose is coordinated, consistent care instead of fragmented visits. The mechanism is better communication and planning between professionals so treatments support each other and respond to changes over time. PMC+1

---

Drug treatments

Important safety note: No drug has been approved specifically to cure or stop autosomal dominant axonal CMT2Z. The medicines below are used to treat symptoms such as neuropathic pain, muscle spasms, mood problems, or sleep issues. Doses are typical adult ranges from FDA labels or clinical references and are not personal medical advice. Never start, stop, or change a dose without a neurologist or prescribing doctor. PMC+1

1. Gabapentin (Neurontin and related brands)
   Gabapentin is an anticonvulsant widely used for neuropathic pain. FDA labels show effective doses for nerve pain between about 900 and 3,600 mg per day, usually divided into three doses. FDA Access Data+2FDA Access Data+2 Its purpose in CMT2Z is to reduce burning, tingling, and shooting pains in the feet and hands. Gabapentin works by binding to the α2δ subunit of voltage-gated calcium channels in nerve cells, which reduces abnormal release of excitatory neurotransmitters. Common side effects include dizziness, sleepiness, swelling in the legs, and weight gain. Any dose must be adjusted for kidney function and started low, then increased slowly. FDA Access Data+1

2. Pregabalin (Lyrica, Lyrica CR)
   Pregabalin is a more potent “cousin” of gabapentin. FDA labeling indicates doses of 150–600 mg per day in divided doses for neuropathic pain conditions such as diabetic neuropathy and postherpetic neuralgia. FDA Access Data+2FDA Access Data+2 In CMT2Z it may be used off-label to relieve nerve pain and improve sleep. It acts on the same α2δ calcium channel target, decreasing excessive nerve firing. Side effects often include dizziness, somnolence, blurred vision, edema, and weight gain. Because it can cause dependence and withdrawal symptoms, it should be tapered under medical supervision. FDA Access Data

3. Duloxetine (Cymbalta)
   Duloxetine is a serotonin–norepinephrine reuptake inhibitor (SNRI) approved for neuropathic pain in diabetic neuropathy and fibromyalgia at 60 mg once daily. FDA Access Data+2FDA Access Data+2 In CMT2Z, it may be prescribed to treat chronic pain and co-existing depression or anxiety. The drug increases serotonin and norepinephrine in pain-modulating pathways in the spinal cord and brain, helping to “turn down” pain signals. Side effects can include nausea, dry mouth, sweating, increased blood pressure, and rare liver effects. It should not be stopped suddenly and must not be combined with certain other antidepressants without careful medical planning. NCBI+1

4. Amitriptyline (tricyclic antidepressant)
   Amitriptyline is an older antidepressant frequently used in low doses (10–75 mg at night) for neuropathic pain. It blocks reuptake of serotonin and norepinephrine and has antihistamine effects, which can improve sleep. The purpose in CMT2Z is night-time pain relief and better rest. Mechanistically it enhances descending pain inhibition but also blocks sodium channels in nerves. Side effects include dry mouth, constipation, blurred vision, weight gain, and sometimes heart rhythm changes, so ECG monitoring may be needed in older or cardiac patients. This medicine is usually avoided or used very carefully in young people and those at risk of overdose. PMC

5. Nortriptyline
   Nortriptyline is a related tricyclic that often has slightly fewer sedating and anticholinergic effects than amitriptyline. Doses for neuropathic pain typically range from 25–100 mg daily, often given at night. Its purpose and mechanism are similar: boosting serotonin and norepinephrine in pain control pathways and stabilizing nerve membranes. Side effects include dry mouth, constipation, dizziness, and possible heart rhythm changes; it should be titrated slowly with medical supervision. It may be chosen when amitriptyline works but causes too much daytime sedation. PMC+1

6. Topical lidocaine 5% patch (Lidoderm and generics)
   Lidocaine 5% patches are approved for postherpetic neuralgia but often used off-label for focal neuropathic pain in the feet or ankles. FDA labeling describes up to three patches applied once daily to intact skin for up to 12 hours. FDA Access Data+2FDA Access Data+2 The purpose is localized pain relief without strong systemic side effects. Lidocaine blocks voltage-gated sodium channels in damaged nerve endings, reducing their ability to fire pain signals. Side effects are usually mild skin irritation or numbness, though rare systemic toxicity can occur if used incorrectly. NHS England+1

7. Capsaicin 8% patch (Qutenza)
   Capsaicin 8% patches are approved for peripheral neuropathic pain such as postherpetic neuralgia and diabetic peripheral neuropathy. FDA Access Data+2European Medicines Agency (EMA)+2 In CMT2Z, a pain specialist might consider them off-label for severe localized foot pain. A single 30–60 minute application in clinic can provide weeks of relief. Capsaicin activates TRPV1 receptors, briefly causing intense burning and then long-lasting reduction in epidermal nerve fiber density and pain signaling. Side effects include burning and redness at the application site, which are managed with local cooling and supportive care. PubMed+1

8. NSAIDs (e.g., naproxen, ibuprofen)
   Nonsteroidal anti-inflammatory drugs are not very effective for pure neuropathic pain, but they can help with secondary muscle or joint pain from altered gait and foot deformities. Typical adult doses include naproxen 250–500 mg twice daily with food, or ibuprofen 200–400 mg every 6–8 hours, within safe limits. Their purpose is to reduce inflammation around sore joints and soft tissues. They work by inhibiting cyclo-oxygenase enzymes and thus prostaglandin synthesis. Side effects include stomach irritation, kidney strain, and increased bleeding risk, especially with long-term use or in older adults. PMC

9. Acetaminophen (paracetamol)
   Acetaminophen is often used as a first-line mild pain reliever, either alone or combined with other agents. Typical adult limits are up to 3,000–4,000 mg per day from all sources, depending on local guidelines and liver health. The purpose is background pain control with fewer gastrointestinal effects than NSAIDs. The mechanism is not fully understood but involves central COX inhibition and modulation of serotonin pathways. Overdose can cause serious liver damage, so total daily intake (including combination products) must be carefully tracked. PMC

10. Baclofen
    Baclofen is a GABA-B receptor agonist used for spasticity. FDA and reference sources describe typical adult oral doses starting at 5 mg three times daily, gradually increased as needed. Mayo Clinic+3FDA Access Data+3DailyMed+3 In CMT2Z, some people develop stiffness or cramps that this medicine can relieve. It decreases excitatory neurotransmitter release in the spinal cord, reducing muscle tone. Side effects include drowsiness, dizziness, weakness, and, if stopped suddenly after high doses, withdrawal symptoms.

11. Tizanidine
    Tizanidine is another antispasticity drug that acts as an α2-adrenergic agonist. Typical adult doses start at 2–4 mg up to three times daily. The purpose is to treat painful muscle spasms and increased tone. It works by reducing excitatory input to motor neurons in the spinal cord. Side effects include low blood pressure, dry mouth, drowsiness, and possible liver enzyme elevation, so monitoring is needed. It may be chosen if baclofen is not tolerated. medicaljournalssweden.se+1

12. Clonazepam
    Clonazepam is a benzodiazepine sometimes used for severe nocturnal cramps, myokymia, or anxiety associated with CMT. Doses are usually very low at bedtime (e.g., 0.25–1 mg) to reduce risk of dependence. It enhances GABA-A receptor function, increasing inhibitory signaling in the nervous system. The purpose is to calm abnormal nerve firing and improve sleep. Side effects include sedation, memory problems, and high dependence potential; long-term use is generally discouraged, especially in young people. PMC

13. Tramadol
    Tramadol is a weak opioid plus serotonin/norepinephrine reuptake inhibitor sometimes used for moderate neuropathic pain when other medicines fail. Typical doses are 50–100 mg every 4–6 hours, with strict daily limits. It acts on µ-opioid receptors and increases monoamines in pain pathways. The purpose is short-term relief of severe pain flares, not long-term daily use. Side effects include nausea, dizziness, constipation, and risk of dependence and serotonin syndrome, especially when combined with other serotonergic drugs. PMC+1

14. Selective serotonin reuptake inhibitors (SSRIs) for mood
    Depression and anxiety are common in chronic neurological disease. SSRIs such as sertraline or escitalopram are used at standard antidepressant doses to treat mood problems, not pain directly. They work by increasing serotonin in brain synapses. The purpose in CMT2Z is to improve mood, coping, and sleep, which indirectly reduces the perceived burden of pain and disability. Side effects vary but may include nausea, headache, and sexual dysfunction. NCBI+1

15. Sleep medicines (short-term, cautious use)
    Short-term use of medicines like melatonin or certain non-benzodiazepine hypnotics may be considered for severe insomnia. The purpose is to break cycles of poor sleep that worsen fatigue and pain. Mechanisms vary: melatonin regulates circadian rhythms; other agents enhance GABA activity. Because many sleep medicines can cause dependence or falls, they must be used carefully, with a focus on behavioural sleep strategies first. NCBI

16. Coenzyme Q10 (as a “drug-like” supplement)
    In a recent CMT2Z case report, oral mecobalamin and coenzyme Q10 were used early in the disease with some clinical improvement. Frontiers CoQ10 acts in mitochondria to support energy production. Some clinicians treat it almost like a drug, at doses such as 100–300 mg per day, although there is no large-scale trial proof in CMT2Z. The purpose is to support nerve and muscle metabolism. Side effects are usually mild, including stomach upset.

17. Mecobalamin (methylcobalamin, active vitamin B12)
    The same CMT2Z report used mecobalamin, an active form of vitamin B12, which is important for myelin and axon health. Frontiers Typical doses in neuropathy studies range from 500–1,500 mcg orally or by injection. The purpose is to correct low B12 and possibly support nerve repair. The mechanism is involvement in methylation reactions and myelin maintenance. Side effects are rare but can include acne-like rash or, in very high doses, hypokalemia as new red blood cells are produced.

18. Vitamin D (if deficient)
    Low vitamin D is common and can worsen muscle weakness and bone fragility. Standard replacement doses (e.g., 800–2,000 IU daily or tailored regimens) are often used. The purpose in CMT2Z is to support bone health and muscle function, reducing fracture risk from falls. The mechanism is regulation of calcium absorption and muscle cell function. Excess doses can cause high calcium levels and kidney problems, so testing and medical advice are essential. PMC

19. Alpha-lipoic acid (ALA)
    ALA is an antioxidant used in some countries as a drug for diabetic neuropathy. Typical studied doses are around 600 mg daily. It works as a cofactor in mitochondrial enzyme complexes and reduces oxidative stress. The purpose in CMT2Z is experimental, aiming to protect nerves from secondary damage. Side effects may include nausea and rarely low blood sugar in people with diabetes. Evidence in genetic neuropathies is limited, so it should be considered an adjunct, not a primary treatment. PMC

20. Pain-modifying combination regimens
    In practice, doctors often combine low doses of several medicines (for example, gabapentin plus duloxetine, or pregabalin plus a topical lidocaine patch) to balance benefits and side effects. PMC+2ilmeridian.com+2 The purpose is multi-target pain control without relying on high doses of any single drug. Mechanistically, different agents act on different parts of the pain pathway – peripheral nerves, spinal cord, and brain – to reduce overall pain signalling. Careful monitoring is needed to avoid drug interactions, excessive sedation, or serotonin syndrome.

---

Dietary molecular supplements

Evidence for supplements in CMT2Z is limited; most data come from other neuropathies. Always discuss supplements with a doctor to avoid interactions with prescription medicines. PMC+1

1. Coenzyme Q10 – 100–300 mg/day with food. Supports mitochondrial energy production and may help tired muscles work more efficiently. It acts as an electron carrier in the respiratory chain and an antioxidant, reducing oxidative stress in nerve cells. Frontiers

2. Methylcobalamin (vitamin B12) – often 500–1,000 mcg/day orally in deficiency or neuropathy. Supports myelin repair, DNA synthesis, and methylation reactions needed for healthy neurons. Frontiers

3. B-complex vitamins – doses vary by product; aim for balanced B1, B6, B12 without megadoses. B vitamins are essential for nerve conduction, neurotransmitter production, and energy metabolism.

4. Alpha-lipoic acid – about 600 mg/day in neuropathy studies. Acts as a powerful antioxidant, regenerating vitamins C and E and improving mitochondrial function, which may reduce oxidative damage in peripheral nerves. PMC

5. Acetyl-L-carnitine – commonly 500–1,000 mg twice daily in research. Helps shuttle fatty acids into mitochondria, improving energy production and possibly nerve regeneration. Some studies in chemotherapy-induced neuropathy show benefit, but evidence in CMT is limited.

6. Omega-3 fatty acids (EPA/DHA) – 1–3 g/day of combined EPA+DHA under medical advice. These fatty acids are incorporated into nerve cell membranes, may reduce inflammation, and support cardiovascular health, which is important for overall function.

7. Vitamin D3 – individualized dose based on blood levels, often 800–2,000 IU/day for maintenance. Supports bone mineralization and muscle performance, reducing fracture risk from falls and helping global strength. PMC

8. Magnesium – 200–400 mg/day, adjusted for kidney function. Magnesium participates in nerve conduction and muscle relaxation and may reduce cramps, although evidence is mixed.

9. Curcumin (turmeric extract) – standardized extracts, often 500–1,000 mg/day, may reduce inflammation and oxidative stress through NF-κB and antioxidant pathway modulation. It should be used cautiously with blood thinners.

10. N-acetylcysteine (NAC) – 600–1,200 mg/day in some neuroprotective studies. It is a precursor of glutathione, a key antioxidant, and may protect nerves from oxidative damage. Evidence in CMT is preliminary and mainly experimental.

---

Immunity-supporting and regenerative / stem-cell–related drugs

At present there are no approved stem-cell or gene therapies specifically for CMT2Z, and no medicine has been proven to regenerate damaged peripheral nerves in this condition. The approaches below are experimental or supportive and must only be used under specialist supervision or in clinical trials. PMC+1

1. Mecobalamin and CoQ10 combination
   As reported in a CMT2Z case, mecobalamin plus CoQ10 was used early and may have helped maintain function. Frontiers Usual oral mecobalamin doses are 500–1,500 mcg/day and CoQ10 100–300 mg/day. The functional goal is to support axon metabolism and myelin repair through improved methylation and mitochondrial energy production. The mechanism is nutritional rather than true regeneration, but it may modestly support surviving nerve fibers.

2. High-dose B vitamins in deficiency
   For patients with documented B1, B6, or B12 deficiency, supervised high-dose replacement can prevent further nerve damage and in some cases improve symptoms. Doses and routes (oral vs injection) depend on lab results. The functional aim is to restore essential co-factors for nerve repair. The mechanism is correction of deficiency-related neuropathy superimposed on genetic disease, not reversal of the genetic defect itself. PMC+1

3. Experimental neurotrophic factor therapies
   Research in inherited neuropathies has explored neurotrophic factors such as NGF or NT-3 delivered by gene therapy or other methods. These treatments aim to promote nerve survival and regrowth but remain in early-stage trials or animal models, with no approved dosing for CMT2Z. The functional goal is true regeneration, but the mechanism and safety are still being studied, so these should only be accessed in regulated clinical trials. PMC

4. Gene therapy and gene-editing approaches
   Because CMT2Z is caused by MORC2 mutations, gene-silencing or gene-editing tools (such as antisense oligonucleotides or CRISPR) are being studied in other forms of CMT and may one day be adapted. PMC+1 There is currently no established dose or approved product for this subtype. The functional mechanism would be to correct or silence the disease gene, preventing further damage, but this is still in the research pipeline.

5. General immune-supportive measures (vaccines, infection control)
   Good vaccination status (e.g., influenza, pneumonia, COVID-19 as recommended by local guidelines) and prompt treatment of infections support overall health and indirectly protect nerves by avoiding severe systemic illness. Dosages follow standard vaccine schedules. The mechanism is immune priming, not “boosting” in a non-specific way, and helps prevent complications that could accelerate functional decline in people with chronic neurological disease.

6. Experimental stem-cell–based therapies
   Various stem-cell approaches are being studied for peripheral neuropathies, including mesenchymal stem cells that might secrete growth factors. These are experimental only, given in tightly controlled trials with individualized dosing and complex protocols. The functional idea is that transplanted cells could support or replace damaged Schwann cells or secrete protective factors. At present, there is no proven, safe, standard stem-cell drug regimen for CMT2Z, and unregulated clinics should be avoided. PMC

---

Surgeries

1. Soft-tissue balancing and tendon transfers
   In many people with CMT, cavovarus deformity (high arch with inward-turned heel) develops because of muscle imbalance. Surgeons may transfer stronger tendons to replace weak ones, for example moving tibialis posterior or extensor hallucis longus to improve dorsiflexion. PubMed+2PubMed+2 The purpose is to rebalance muscle forces so the foot becomes flatter, more stable, and easier to walk on. Mechanistically, tendon transfer changes the direction of pull so that walking loads are spread more evenly and deformity progression slows.

2. Osteotomies (bone cuts and realignment)
   When deformities become fixed, bones may be cut and repositioned, such as first metatarsal dorsiflexion osteotomy or calcaneal valgus osteotomy. www.elsevier.com+2PubMed+2 The aim is to correct forefoot and hindfoot alignment so that the foot can sit flat on the ground. By changing bone angles, the surgeon allows tendons and ligaments to work in more normal positions, improving gait and reducing pressure points that cause pain and calluses.

3. Plantar fascia release
   The plantar fascia under the foot can become very tight in cavus deformity. A partial release or fasciotomy may be performed, often combined with osteotomies and tendon transfers. PubMed+1 The purpose is to relieve tension that maintains the high arch and clawing of the toes. Mechanistically, cutting part of this thick band allows the arch to relax, making it easier to reposition the bones of the foot and redistribute pressures.

4. Corrective toe surgery (e.g., hammertoe correction)
   Clawed or hammertoes can rub in shoes, causing pain and ulcers. Surgical straightening, tendon lengthening, or small joint fusion may be offered. Charcot-Marie-Tooth Disease+2enmc.org+2 The purpose is pain relief, easier shoe fitting, and improved toe grip and balance. Mechanistically, altering tendon length and small bone positions removes the forces that bend the toes abnormally and allows them to share weight more evenly.

5. Arthrodesis (joint fusion, reserved for severe cases)
   When deformity is extreme and joints are very unstable or arthritic, fusion of certain joints may be recommended, usually as a last resort. Charcot-Marie-Tooth Disease+2jfootankle.com+2 The purpose is to create a stable, pain-free foot, even though some motion is lost. The mechanism is mechanical: by permanently joining bones, the joint can no longer deform or rub abnormally, which reduces pain and improves the platform for walking.

---

Prevention and lifestyle strategies

1. Have regular neurologist and physiotherapy reviews to detect changes early. PMC+1

2. Use braces, shoes, and insoles as prescribed to prevent falls and deformity. Charcot-Marie-Tooth Association+1

3. Maintain a healthy body weight to reduce stress on weak feet and joints. PMC

4. Keep physically active with safe, low-impact exercises such as cycling or swimming. MDPI+1

5. Avoid smoking, which can reduce blood flow to nerves and muscles. PMC

6. Manage diabetes, thyroid problems, or vitamin deficiencies aggressively if present, as they can worsen neuropathy. PMC+1

7. Protect feet with daily inspection, moisturising, and prompt care of blisters or sores. Wikipedia+1

8. Use home safety measures (grab bars, non-slip mats, good lighting) to prevent falls. Charcot-Marie-Tooth Association

9. Stay up to date with vaccinations to prevent severe infections that might reduce overall strength. PMC

10. Seek psychological and social support to manage stress, depression, or anxiety related to chronic illness. NCBI

---

When to see a doctor

You should see a doctor – ideally a neurologist familiar with CMT – if you notice new weakness, more frequent tripping, sudden changes in walking pattern, or new deformity of your feet or hands. Sudden severe pain, rapid loss of sensation, or changes in bladder or bowel control also need urgent assessment to rule out other conditions such as spinal cord problems. Europe PMC+1 Persistent unrelieved pain, weight loss, fevers, or severe fatigue should be checked to see whether a second illness has appeared. It is also important to see a doctor before starting any new drug or supplement, and before surgery, pregnancy, or major life changes, so your care plan can be updated safely. PMC

---

What to eat and what to avoid

1. Eat: a balanced diet rich in fruits, vegetables, whole grains, lean protein, and healthy fats to support general health and muscle function. Avoid: crash diets or very low-calorie plans that cause rapid weight loss and muscle wasting. PMC

2. Eat: foods high in B vitamins (whole grains, eggs, dairy, legumes) if tolerated. Avoid: relying only on processed foods that are low in micronutrients. PMC+1

3. Eat: sources of omega-3 (fatty fish, flaxseed, walnuts) several times per week. Avoid: very high intake of trans fats and deep-fried fast foods that increase inflammation and cardiovascular risk.

4. Eat: calcium- and vitamin-D–rich foods (dairy, fortified products, leafy greens) if suitable. Avoid: high-sugar soft drinks that weaken bone and add empty calories. PMC

5. Eat: adequate protein from fish, poultry, legumes, or tofu to preserve muscle mass. Avoid: long periods with very low protein intake, which can accelerate muscle loss.

6. Drink: plenty of water to support circulation and prevent constipation from some medicines. Avoid: excessive alcohol, which can directly damage nerves and worsen balance. PMC

7. Eat: high-fiber foods (vegetables, fruits with skin, beans) to support bowel health and weight control. Avoid: very high-salt, highly processed snacks that can raise blood pressure and cause swelling.

8. Use: spices such as turmeric and ginger in cooking for potential mild anti-inflammatory benefits. Avoid: self-prescribing large doses of herbal extracts without medical advice, as interactions with drugs are possible.

9. Prioritize: regular meal times to stabilize energy and avoid big sugar swings that worsen fatigue. Avoid: frequent sugary snacks and energy drinks that give a quick boost but then a “crash.”

10. Consider: individualized nutrition counselling if you have diabetes, kidney disease, or other conditions that affect diet. Avoid: following extreme internet diets that are not personalized or evidence-based. PMC+1

---

Frequently asked questions

1. Is autosomal dominant axonal CMT2Z curable?
   At present CMT2Z cannot be cured. The genetic change in MORC2 stays for life. However, many people can live active lives for decades with good rehabilitation, bracing, and symptom-based treatment. Research into gene therapy and disease-modifying drugs is active but still experimental. nature.com+1

2. Will everyone with CMT2Z end up in a wheelchair?
   No. The course of CMT2Z varies widely. Some people develop significant disability and may use a wheelchair, especially for long distances, while others remain able to walk with braces and supports. Early physiotherapy, good footwear, and prevention of falls can delay or reduce the need for wheelchairs. Orpha+1

3. Can exercise make the disease worse?
   Appropriate, guided exercise usually helps rather than harms. Over-strenuous or high-impact activities that cause repeated injury can be harmful, but gentle strength, stretching, and aerobic exercise prescribed by a physiotherapist are generally safe and beneficial. MDPI+2SAGE Journals+2

4. Is CMT2Z only a nerve disease, or can it affect other organs?
   CMT2Z mainly affects peripheral nerves and the muscles they supply. Some people may have additional features such as scoliosis or, rarely, involvement of other systems, but the core problem is neuropathy. Any new non-neurological symptoms should still be checked by a doctor, as they may be unrelated conditions. Orpha+2NCBI+2

5. Can children be tested for the family MORC2 mutation?
   Genetic testing is possible if the family mutation is known, but the decision is complex and usually guided by a genetic counsellor. Testing minors is often considered when there are symptoms, or when results will clearly change management. Orpha+1

6. Are there special precautions for surgery or anesthesia?
   People with CMT should tell surgeons and anesthesiologists about their diagnosis. Certain neuromuscular-blocking drugs and positions during surgery may need extra caution to avoid nerve compression or respiratory compromise. A pre-operative assessment helps plan safe anesthesia and recovery. PMC

7. Does pregnancy worsen CMT2Z?
   Some women with CMT notice temporary worsening of symptoms during pregnancy due to weight gain and hormonal changes, while others do not. Careful monitoring, safe exercise, and planning for delivery with the obstetric and neurology teams are important. PMC+1

8. Can CMT2Z be confused with other diseases?
   Yes. Other inherited neuropathies, spinal cord disorders, or muscular dystrophies can look similar. Nerve conduction studies, EMG, and genetic testing help confirm the diagnosis and distinguish CMT2Z from these conditions. Europe PMC+1

9. Is it safe to use over-the-counter pain medicines?
   Common medicines like acetaminophen or ibuprofen may be safe for many people, but they still carry risks, especially for the liver, kidneys, or stomach. It is best to discuss all medicines – even over-the-counter ones – with your doctor, particularly if you also take prescription drugs for CMT symptoms. PMC

10. Do braces weaken muscles?
    Properly prescribed braces should not significantly weaken muscles. They are used when muscle power is already reduced, to prevent falls and deformities. In fact, braces can make it possible to exercise more safely, which helps preserve remaining strength. Charcot-Marie-Tooth Association+1

11. Should people with CMT2Z avoid all sports?
    They do not need to avoid sports completely. Low-impact activities such as swimming, cycling, or carefully chosen gym programs are often encouraged. High-impact or contact sports may increase risk of falls and injury and should be discussed with the healthcare team. MDPI+1

12. Is there any role for alternative therapies?
    Some people try acupuncture, massage, or yoga to manage pain and stiffness. Evidence is limited, but these may be helpful as long as they are used in addition to, not instead of, evidence-based care, and are provided by qualified practitioners who understand CMT. Always tell your doctor about any alternative treatments. PMC+1

13. Can CMT2Z shorten life expectancy?
    Most people with CMT, including CMT2Z, have a near-normal life span, although they may live with significant physical disability. Life expectancy can be affected by complications such as falls, severe deformities, or unrelated illnesses, which is why good preventive care is important. SAGE Journals+1

14. How often should follow-up visits be scheduled?
    The frequency depends on disease severity and age. Many people benefit from yearly neurologist visits and more frequent physiotherapy or orthotic reviews. Rapid changes in symptoms should trigger earlier appointments. PMC+1

15. Where can families find reliable information and support?
    Patient organizations and specialist clinics for CMT, as well as reputable medical websites and peer-reviewed articles, are good sources. Examples include national CMT associations and Orphanet entries on CMT2Z. Charcot-Marie-Tooth Association+2Orpha+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 23, 2025.