Charcot-Marie-Tooth Disease Caused by Mutation in PLEKHG5

Charcot-Marie-Tooth disease caused by mutation in PLEKHG5 is a rare inherited nerve disease that mainly affects the long nerves to the feet and hands. It is classified as Charcot-Marie-Tooth disease recessive intermediate type C (CMTRIC) and happens when a child receives a faulty copy of the PLEKHG5 gene from both parents (autosomal recessive). The disease causes damage to both the nerve fiber (axon) and its insulating cover (myelin), so nerve signals travel more slowly and less strongly to the muscles and skin. This leads to progressive weakness and shrinking of muscles in the feet and legs first, and later in the hands, together with loss of feeling in the same areas.GARD Information Center+3Neurology Asia+3Institut de Myologie+3

Charcot-Marie-Tooth (CMT) disease is a group of inherited nerve disorders that slowly damage the long nerves in the arms and legs. When the disease is caused by a mutation in the PLEKHG5 gene, it usually leads to weakness and wasting of the muscles in the feet, legs, and sometimes hands, with problems in walking and balance. This type is rare, and there is no cure yet, but many supportive treatments can reduce symptoms and improve quality of life.PMC+1

PLEKHG5 is a gene on chromosome 1p36 that makes a protein important for nerve cell health and for support cells around the nerves called Schwann cells. This protein helps control cell shape, nerve connections (synapses), dendrite growth, and survival signals, especially through a pathway called NF-κB in the peripheral nervous system. When both copies of PLEKHG5 are changed (mutated), the protein cannot work normally, so peripheral nerves slowly become damaged and cannot carry messages properly. This long-term nerve damage is what produces the clinical picture of intermediate Charcot-Marie-Tooth disease.Neurology Asia+2Wiley Online Library+2

How Does PLEKHG5 Mutation Cause CMT?

The PLEKHG5 gene gives instructions for a protein that helps nerve cells keep their structure and communicate with other cells. When this gene has harmful mutations, the motor nerves that carry signals from the spinal cord to muscles can slowly stop working properly. This can cause an intermediate form of CMT (sometimes called CMT type C) or related motor neuron diseases. The result is muscle weakness, foot deformities, reduced reflexes, and sometimes sensory changes, usually starting in childhood or teenage years and progressing over time.Institut de Myologie+2SpringerLink+2

Doctors treat CMT from PLEKHG5 mutation in the same way as other forms of CMT: through rehabilitation therapy, orthoses (braces), pain control, and surgery for severe foot deformities. Research is ongoing into gene and regenerative therapies, but these are still experimental and not yet standard care.PMC+1

Other names and types

This condition has several other names in the medical literature:

• Charcot-Marie-Tooth disease recessive intermediate C

• Charcot-Marie-Tooth disease recessive intermediate type C

• Autosomal recessive intermediate Charcot-Marie-Tooth disease type C (AR-CMTRIC)

• Charcot-Marie-Tooth disease caused by mutation in PLEKHG5

• CMTRIC due to PLEKHG5 mutation

These names all refer to the same basic disease: an intermediate form of Charcot-Marie-Tooth where the main cause is harmful changes in both copies of the PLEKHG5 gene. Different databases (such as Malacards, NORD and disease ontologies) use slightly different wording, but they point to the same genetic condition.GARD Information Center+3National Organization for Rare Disorders+3MalaCards+3

Types 

Doctors sometimes talk about “types” based on how the PLEKHG5 mutation shows itself in patients:

1. PLEKHG5-related intermediate CMT (CMTRIC) – this is the main type the question is about. It shows mixed axonal and demyelinating features on nerve tests, with distal weakness, foot deformities, and sensory loss.Institut de Myologie+2MalaCards+2

2. PLEKHG5-related lower motor neuron disease / distal spinal muscular atrophy – some PLEKHG5 mutations cause a different but related disease where motor neurons are more affected and sensory loss is less obvious. These patients can also have generalized weakness and early breathing problems.PubMed+2Wiley Online Library+2

These are not completely separate diseases but points on a spectrum of disorders caused by different PLEKHG5 mutations, which is why the same gene can be linked to both intermediate CMT and lower motor neuron disease in different families.Neurology Asia+2PubMed+2

Causes

1. Homozygous PLEKHG5 mutation
   The main direct cause of this disease is a homozygous mutation in PLEKHG5, meaning both copies of the gene carry the same harmful change. When no normal copy of the gene is present, the nerve cells cannot make enough working PLEKHG5 protein, and peripheral nerves slowly become damaged. This pattern has been shown in several families where affected children have two mutated copies and healthy parents have only one.Neurology Asia+2Institut de Myologie+2

2. Compound heterozygous PLEKHG5 mutations
   In some families, the child has two different harmful mutations in PLEKHG5, one from each parent; this is called compound heterozygosity. Even though the exact mutation is different on each allele, together they still prevent normal protein function and cause intermediate CMT. Studies have reported compound heterozygous PLEKHG5 variants in patients with childhood-onset sensory-motor neuropathy.PubMed+2Springer Medizin+2

3. Loss of normal PLEKHG5 protein function
   Most PLEKHG5 mutations either shorten the protein (truncating variants) or change important amino acids (missense variants) so the protein cannot fold or signal correctly. Functional studies show that such changes reduce or abolish the protein’s normal activity in nerve cells, leading over time to degeneration of motor and sensory fibers.Institut de Myologie+2PubMed+2

4. Disruption of NF-κB–related survival signaling
   PLEKHG5 helps activate NF-κB, a signaling pathway that supports cell survival, especially in neurons and Schwann cells. When PLEKHG5 is defective, this survival pathway is weakened, making the peripheral nerves more vulnerable to injury and age-related damage. Over years, this contributes to chronic neuropathy and the progressive nature of the disease.Wiley Online Library+2Neurology Asia+2

5. Abnormal Schwann cell function
   Schwann cells wrap around peripheral axons to form myelin, which speeds up nerve conduction. PLEKHG5 is expressed in Schwann cells, and loss of its function leads to dysmyelination – a problem with making or maintaining normal myelin. This explains why nerve conduction studies show intermediate or mixed demyelinating and axonal changes in these patients.Neurology Asia+2Orpha+2

6. Abnormal neuron structure and synapse formation
   Animal and cell studies indicate that PLEKHG5 is involved in shaping neurons, forming dendrites, and building synapses. When PLEKHG5 is missing or faulty, these structures can form incorrectly or be unstable, which interferes with how nerve cells connect and communicate. Over time this structural problem contributes to poor motor control and weakness.Neurology Asia+2Wiley Online Library+2

7. Axonal degeneration of peripheral nerves
   In nerve biopsies from patients, doctors often see axonal neuropathy, meaning the long part of the nerve (axon) is damaged or lost. When axons degenerate, signals cannot reach the muscles or skin properly, leading to weakness, wasting, and sensory loss. Axonal loss is a key microscopic cause of the symptoms in PLEKHG5-related CMT.PubMed+2Neurology Asia+2

8. Mixed demyelinating and axonal features
   Sural nerve biopsies and nerve conduction studies often show a mixture of demyelinating changes (slowed conduction) and axonal loss (reduced amplitudes). This “intermediate” pattern is why the disease is called intermediate CMT rather than purely demyelinating or purely axonal. The mixed pathology is a cause of both reduced speed and reduced strength of nerve signals.NCBI+2MalaCards+2

9. Autosomal recessive inheritance from carrier parents
   The inheritance pattern itself is a cause at the genetic level. Each parent carries one mutated copy of PLEKHG5 but usually has no symptoms because the other copy is normal. When a child inherits the mutated copy from both parents, there is no normal gene left, and the disease appears. This explains why the condition is more common in families with consanguinity.Neurology Asia+2Institut de Myologie+2

10. Consanguinity and small gene pools
    Several case reports describe affected children from consanguineous (related) parents or from small, isolated communities. In such families, the same rare PLEKHG5 mutation can be passed down through both parents, raising the chance that a child receives two mutated copies. This social and population factor increases the likelihood of the genetic cause expressing itself.Institut de Myologie+2Springer+2

11. Missense mutations in critical domains
    Some patients have missense mutations that change single amino acids in important domains of the PLEKHG5 protein. These changes can disturb how the protein interacts with other molecules or cell membranes, leading to a “gain of bad function” or “loss of good function.” Even though the protein is still made, its altered behavior can cause the neuropathy.Springer+2Neurology Asia+2

12. Truncating or nonsense mutations
    Other patients have nonsense or frameshift mutations that produce a shortened, non-functional protein or trigger nonsense-mediated decay of the mRNA. In these cases, there is very little or no PLEKHG5 protein in nerve tissue, and the severe loss of function directly causes early and more pronounced neuropathy.Institut de Myologie+2Neurology Asia+2

13. Splice-site mutations affecting RNA processing
    Splice-site mutations, reported in some PLEKHG5-CMT families, disturb how the gene’s RNA is cut and joined. This leads to abnormal or missing parts of the protein. Because the protein domains are arranged in a specific way for proper signaling, even small splice errors can result in a dysfunctional protein that contributes to disease.Neurology Asia+2PubMed+2

14. Length-dependent nerve vulnerability
    Long peripheral nerves to the feet and hands are especially vulnerable to genetic damage. In PLEKHG5-related CMT, this length-dependent vulnerability means distal nerves fail first, which is why symptoms start in the feet. The great length of these axons increases the energy demand and makes them more sensitive to defects in intracellular transport and signaling.NCBI+2physio-pedia.com+2

15. Distal muscle denervation and atrophy
    As peripheral nerves degenerate, the muscles they supply lose their nerve input (denervation). Over time, denervated muscles shrink (atrophy) and weaken, and this muscular atrophy itself becomes a direct cause of disability, difficulty walking, and foot deformities. MRI studies in CMT show this distal muscle atrophy and fatty replacement clearly.PubMed+2PMC+2

16. Foot deformities secondary to muscle imbalance
    Weakness of some muscles and relative strength of opposing muscles leads to pes cavus (high arched foot), hammer toes, and other deformities. Once these deformities appear, they further worsen walking and balance, creating a loop where structural change becomes a cause of more falls and pain. Pes cavus is strongly associated with CMT neuropathies.NCBI+2PMC+2

17. Spinal and posture problems from long-term weakness
    Long-standing muscle weakness, especially in the trunk and proximal muscles, can contribute to scoliosis or abnormal posture in some patients. These spine and posture problems can cause extra pressure on nerves and joints, indirectly adding to pain and fatigue. Thus, chronic weakness and deformity feed back into the overall disease burden.NCBI+2Wiley Online Library+2

18. General CMT molecular pathways (transport, mitochondria)
    CMT in general involves disruption of important cell processes like intracellular transport, mitochondrial function, and protein quality control. Even though each gene is different, many CMT genes, including PLEKHG5, converge on these shared pathways. When these processes fail, the health of long peripheral axons declines, which is another mechanistic cause of neuropathy.Wikipedia+2physio-pedia.com+2

19. Modifier genes and background genetics
    Not all people with the same PLEKHG5 mutation have identical symptoms, suggesting that other genes modify the effect of the main mutation. These modifier genes can make the neuropathy milder or more severe, so they act as hidden causes of variation in nerve damage, even though PLEKHG5 is the primary gene.Wiley Online Library+2PFM Journal+2

20. Time and chronic progression
    Finally, time itself is a practical cause of worsening disease. Because this is a slowly progressive hereditary neuropathy, damage builds up year after year. Axons degenerate, muscles atrophy, and deformities become fixed, turning a genetic mutation present from birth into a visible clinical disease over childhood and adulthood.NCBI+2physio-pedia.com+2

Symptoms

1. Progressive weakness in the feet and lower legs
   The earliest and most common symptom is slowly increasing weakness in the feet and ankles. Children may trip often, have trouble running, or develop a “slapping” or high-steppage gait because they cannot lift the front of the foot well (foot drop). This happens because the distal leg muscles lose their nerve supply first.GARD Information Center+3NCBI+3Orthobullets+3

2. Muscle wasting (atrophy) of the calves and feet
   Over time, the muscles in the lower legs and feet become visibly thinner, giving an “inverted champagne bottle” appearance to the calves. This wasting reflects the long-term denervation from damaged peripheral nerves and is a hallmark of CMT, including PLEKHG5-related forms.GARD Information Center+3NCBI+3Orthobullets+3

3. Foot deformities such as pes cavus and hammer toes
   Many patients develop high-arched feet and curled toes, known as pes cavus and hammer toes. These deformities are caused by chronic muscle imbalance around the foot and ankle and can make shoe fitting difficult and walking painful. Orthopedic studies show pes cavus is strongly linked with CMT-type neuropathies.NCBI+2PMC+2

4. Distal sensory loss (numbness) in the feet
   Loss of feeling (sensory impairment) in the feet is another key symptom. Patients often describe numbness, reduced ability to feel temperature or pain, or a “stocking” distribution where the lower legs feel dull. This occurs because sensory fibers in the peripheral nerves are damaged along with motor fibers.GARD Information Center+3NCBI+3MalaCards+3

5. Tingling, burning, or neuropathic pain
   Some people experience tingling, pins-and-needles, burning, or aching pain in the feet and sometimes the hands. This type of pain is called neuropathic pain and comes from abnormal nerve signaling in damaged sensory fibers. It can disturb sleep and affect mood and daily activities.Cleveland Clinic+2physio-pedia.com+2

6. Absent or reduced tendon reflexes
   On examination, doctors often find that ankle and knee reflexes are weak or absent. This happens because the reflex arc depends on intact sensory and motor nerve fibers, which are damaged in CMTRIC. Loss of deep tendon reflexes is a classic sign of hereditary motor and sensory neuropathies.GARD Information Center+3NCBI+3NCBI+3

7. Balance problems and unsteady gait
   Because feeling in the feet is reduced and the muscles are weak, many patients have poor balance, especially in the dark or on uneven ground. They may sway when standing with feet together or need to watch their feet while walking. This unsteady gait increases the risk of falls.Orthobullets+2Charcot-Marie-Tooth Association+2

8. Hand weakness and fine motor difficulties
   As the disease progresses, the hands can also be affected. People may notice trouble doing buttons, writing, using tools, or holding small objects. The small muscles of the hands depend on long nerves that, like those in the legs, are vulnerable to PLEKHG5-related damage.Cleveland Clinic+3NCBI+3Charcot-Marie-Tooth Association+3

9. Fatigue with walking and daily activities
   Because muscles are weak and nerves are inefficient, simple activities such as walking, climbing stairs, or standing for long periods become tiring. Patients may need frequent rest breaks and feel that their legs “give out” quickly compared with other people. This fatigue is a common but often under-recognized symptom.NCBI+2Charcot-Marie-Tooth Association+2

10. Cramps and muscle tightness
    Some individuals report painful muscle cramps, especially in the calves and feet. Cramping may occur after exertion or at night and is thought to result from unstable nerve firing in partially damaged motor units. It can disturb sleep and further reduce quality of life.Charcot-Marie-Tooth Association+2physio-pedia.com+2

11. Toe-walking or abnormal foot posture in children
    Children with CMTRIC may toe-walk or stand with unusual foot positions because of weakness and tight tendons. Parents may notice that their child is clumsy, falls more than peers, or has difficulty keeping up in sports, which can be an early sign of hereditary neuropathy.NCBI+2Charcot-Marie-Tooth Association+2

12. Spinal or postural deformities (e.g., scoliosis)
    In some patients, long-standing muscle imbalance around the trunk and spine can lead to mild scoliosis or other posture changes. These spinal issues may add back pain or discomfort to the burden of peripheral neuropathy, though they are not present in all cases.NCBI+2Wiley Online Library+2

13. Slowly progressive course over years
    The symptoms usually worsen very slowly over many years. A child who is mildly affected may walk independently for many years but gradually need orthotic devices or assistive tools in adulthood. This slow progression is typical of hereditary CMT disorders and distinguishes them from rapidly progressive acquired neuropathies.NCBI+2physio-pedia.com+2

14. Preserved life expectancy with functional limitations
    Most people with CMT, including PLEKHG5-related forms, have a near-normal life span, but they live with physical limitations and increased disability. Daily activities may be restricted by weakness, deformity, pain, and fatigue rather than by life-threatening complications.Cleveland Clinic+2physio-pedia.com+2

15. Emotional and social impact
    Chronic disability, visible foot deformities, and difficulty participating in sports or school activities can cause emotional stress, anxiety, or low mood. These psychological effects do not come directly from the gene but are real consequences of living with a long-term neurological disease and should also be recognized and supported.Cleveland Clinic+2NCBI+2

Diagnostic tests

Physical examination

1. Neurological examination of strength and sensation
   The first and most important test is a detailed neurological exam. The doctor checks muscle strength in the feet, legs, hands, and arms; tests sensation to light touch, pinprick, vibration, and joint position; and looks for signs of muscle wasting. This step helps confirm a length-dependent peripheral neuropathy pattern typical of CMT.NCBI+2physio-pedia.com+2

2. Assessment of tendon reflexes
   The clinician tests knee and ankle reflexes using a reflex hammer. In PLEKHG5-related CMT, deep tendon reflexes are often reduced or absent, especially at the ankles, which supports a diagnosis of peripheral neuropathy rather than a central nervous system problem.GARD Information Center+3NCBI+3NCBI+3

3. Gait and balance evaluation
   The doctor observes how the patient walks, turns, and stands, including heel, toe, and tandem walking. A high-steppage gait, foot drop, and balance difficulty, especially with eyes closed, point toward sensory-motor neuropathy. This clinical testing helps decide whether further nerve studies are needed.Orthobullets+2Charcot-Marie-Tooth Association+2

4. Orthopedic examination of feet and spine
   Foot shape, ankle alignment, and spine curvature are inspected to identify pes cavus, hammer toes, Achilles tendon tightness, or scoliosis. Recognizing these deformities early is important for planning physiotherapy, braces, or possible surgery.PMC+2Ovid+2

Manual tests

5. Manual muscle testing (MRC grading)
   The clinician uses manual resistance to grade muscle strength in key muscle groups (for example ankle dorsiflexors, plantarflexors, hand muscles) using the Medical Research Council (MRC) scale. This structured manual testing shows which muscles are weakest and helps track disease progression over time.NCBI+2Wiley Online Library+2

6. Functional tests such as timed walking or rising from a chair
   Simple timed tasks – like walking a set distance, climbing stairs, or standing up from a chair without using hands – give a practical measure of how neuropathy affects daily movements. These manual functional tests are often used in clinics and research studies to monitor CMT severity and treatment response.PMC+2ScienceDirect+2

7. Grip strength and hand function tests
   Hand-held dynamometers or simple grip tasks can measure hand strength. Buttoning a shirt, writing, or using small objects can be observed to evaluate fine motor function. These manual tests are important because upper-limb involvement may appear later in the disease course.Charcot-Marie-Tooth Association+2physio-pedia.com+2

Laboratory and pathological tests

8. Genetic testing for PLEKHG5 mutations
   Molecular genetic testing is the definitive test for this condition. Sequencing the PLEKHG5 gene in blood or saliva can identify homozygous or compound heterozygous pathogenic variants that confirm CMTRIC due to PLEKHG5. Many clinical genetic panels now include PLEKHG5 among CMT-associated genes.MalaCards+3Invitae+3Neurology Asia+3

9. Broader CMT or neuropathy gene panels
   If the exact cause is not known, broader gene panels or exome sequencing may be done. These tests analyze many neuropathy genes at once, which helps distinguish PLEKHG5-related CMTRIC from other forms of CMT caused by genes like PMP22, MFN2, or GDAP1.Wikipedia+3Institut de Myologie+3PubMed+3

10. Routine blood tests to rule out acquired causes
    Basic laboratory tests (such as blood sugar, vitamin B12, thyroid function, kidney and liver tests) are often done to exclude common acquired causes of neuropathy. While these tests do not diagnose PLEKHG5-CMT directly, normal results support a hereditary cause.Mayo Clinic+2nhs.uk+2

11. Creatine kinase (CK) level
    Some patients with neuromuscular disease have mildly elevated CK, a muscle enzyme, due to chronic muscle damage. CK is not specific for CMT but can help distinguish primary muscle disease from nerve disease and may be slightly raised in some hereditary neuropathies.NCBI+2Wiley Online Library+2

12. Nerve or skin biopsy with pathology
    In selected cases, a sural nerve biopsy or skin biopsy is performed. Pathology may show reduced myelinated fibers, axonal loss, and mixed demyelinating and axonal changes consistent with intermediate CMT. Skin biopsies can show reduced intra-epidermal nerve fiber density in distal legs. These findings support the diagnosis when genetic results are unclear.MalaCards+3PubMed+3Neurology Asia+3

Electrodiagnostic tests

13. Nerve conduction studies (NCS)
    NCS measure how fast and how strongly electrical signals travel along nerves. In PLEKHG5-related CMTRIC, NCS typically show moderately slowed conduction velocities and reduced amplitudes, reflecting a mixed demyelinating and axonal neuropathy. This intermediate pattern helps separate CMTRIC from purely demyelinating or purely axonal CMT.MalaCards+3NCBI+3Hopkins Medicine+3

14. Electromyography (EMG)
    EMG uses a small needle electrode to record muscle electrical activity. In hereditary neuropathy, EMG often shows chronic denervation, such as large-amplitude, long-duration motor unit potentials. EMG complements NCS and confirms that muscle weakness is due to nerve damage, not a primary muscle disease.umms.org+3NCBI+3Cleveland Clinic+3

15. F-wave and late response testing
    Special parts of the nerve conduction study, such as F-waves, look at conduction in the entire length of the motor nerve. Abnormal F-waves can further support the presence of generalized peripheral neuropathy and help characterize how diffuse the nerve involvement is in CMT.NCBI+2Neuropathy Commons+2

16. Quantitative sensory testing (QST)
    QST uses controlled stimuli (such as vibration or temperature changes) to measure sensory thresholds. While not specific for PLEKHG5-CMT, QST can document the degree of sensory loss, especially in clinical studies monitoring disease severity and progression.NCBI+2physio-pedia.com+2

Imaging tests

17. MRI of lower-limb muscles
    Muscle MRI of the legs can show patterns of muscle atrophy and fatty replacement. In CMT, including intermediate forms, MRI often reveals more severe fat replacement in distal calf muscles than in proximal thigh muscles, matching clinical weakness. This pattern has been described in CMT cohorts and helps distinguish hereditary neuropathies from other conditions.PLOS+3PubMed+3PMC+3

18. Whole-body or regional MRI for disease pattern
    In some research settings, whole-body or extended MRI is used to map muscle involvement along the limbs. Different CMT genotypes can show distinct patterns of fatty change, so this imaging may help narrow down the list of possible genes and provides an objective biomarker of disease progression.OUP Academic+2Springer+2

19. Spinal imaging if scoliosis or other concerns are present
    If the patient has significant scoliosis or unusual neurologic signs, MRI of the spine may be done to rule out other causes of foot deformity or weakness (such as spinal cord lesions). A normal spine image supports the diagnosis of a primary peripheral neuropathy like CMT rather than a central problem.PMC+2Ovid+2

20. Ultrasound of peripheral nerves and muscles (in some centers)
    High-resolution ultrasound can visualize enlarged or abnormal peripheral nerves and can also show muscle wasting. Although ultrasound is not yet standard for diagnosing PLEKHG5-CMT, it is increasingly used as a non-invasive tool to study hereditary neuropathies and may add extra information in expert centers.Neuromuscular+2neurology.org+2

Non-Pharmacological Treatments

1. Regular physiotherapy and stretching
Physiotherapy is one of the most important treatments for Charcot-Marie-Tooth disease caused by PLEKHG5 mutation. A physiotherapist guides gentle stretching and range-of-motion exercises to keep joints flexible and reduce the risk of contractures, where muscles and tendons become permanently tight. Regular stretching of ankles, calves, and hamstrings can slow down stiffness and make walking safer and easier in daily life.nhs.uk+1

2. Strength training for weak muscles
Light strength training focuses on the muscles that still work, especially those around the hips, knees, and core, to support weaker feet and ankles. Using body-weight, resistance bands, or light weights, exercises are chosen to avoid over-fatigue. The purpose is to maintain strength as long as possible, slow progression of disability, and improve balance and walking stability.physio-pedia.com+1

3. Balance and proprioception exercises
Because damaged nerves send weaker signals from the feet, people with CMT often lose their “position sense.” Simple balance exercises such as standing on one leg with support, walking on different surfaces, or using balance boards can train the brain to adapt. The goal is to reduce falls, improve confidence in walking, and support safer movement at home, school, or work.physio-pedia.com+1

4. Occupational therapy (OT)
Occupational therapists help patients manage daily tasks such as dressing, writing, cooking, and using devices like phones and computers. They recommend adaptive tools like built-up pens, special cutlery, or button hooks. The purpose is to keep independence and reduce frustration by adapting activities to the person’s abilities, not forcing the person to fit the task.Muscular Dystrophy Association+1

5. Ankle-foot orthoses (AFOs)
AFOs are braces that support the ankle and foot, especially in people with foot drop or high-arched feet. They hold the foot in a better position, reduce tripping, and make walking smoother and less tiring. By keeping the foot aligned, AFOs can also prevent long-term deformity and lessen joint strain.Charcot-Marie-Tooth Association+2Charcot-Marie-Tooth Disease+2

6. Custom footwear and insoles
Special shoes and insoles help spread pressure evenly under the foot, protect areas at risk of calluses and ulcers, and support high arches or hammertoes. A podiatrist or orthotist can design footwear that works together with braces. The purpose is to reduce pain, improve stability, and prevent skin breakdown that could become serious infections.London Orthotics+1

7. Hand splints and adaptive hand devices
If hand muscles become weak, light splints or wrist supports may help steady the hand for writing, typing, or holding utensils. OT may also suggest jar openers or grip aids. This reduces hand fatigue and allows finer tasks to remain possible for longer, protecting independence at school and home.Muscular Dystrophy Association+1

8. Aerobic exercise (walking, swimming, cycling)
Low-impact aerobic exercise improves heart and lung health and helps control weight without over-stressing weak muscles. Activities such as swimming, stationary cycling, or brisk walking with supports can be adjusted to each person. Aerobic fitness supports better endurance for daily activities and may improve mood and sleep.ResearchGate+1

9. Gait training and assistive devices
Physiotherapists teach efficient walking patterns, sometimes using canes, trekking poles, or walkers. Learning how to place the feet, how wide to step, and how to turn safely reduces fatigue and risk of falls. Assistive devices can be adjusted over time as the disease slowly progresses.physio-pedia.com+1

10. Podiatry and regular foot care
Regular visits to a podiatrist help manage thick nails, corns, calluses, and pressure points on the feet. This care is important because reduced sensation means small injuries may go unnoticed. Good foot care prevents infections, ulcers, and deformities that can seriously affect mobility.Muscular Dystrophy Association+1

11. Home modifications and fall-prevention
Simple changes at home—removing loose rugs, improving lighting, installing grab bars and handrails, and using non-slip mats—can lower the chance of tripping. The purpose is to create a safer environment that matches the person’s balance and strength, lowering the risk of fractures and hospital visits.Springer+1

12. Weight management and healthy lifestyle
Extra body weight makes walking harder and increases stress on weak ankles and feet. A balanced diet plus regular light activity helps maintain a healthy weight. This reduces joint strain, improves energy, and can lower the risk of other diseases like diabetes, which could further worsen nerve problems.PMC+1

13. Energy conservation and fatigue management
People with CMT often experience fatigue because their muscles work harder to perform simple tasks. Learning to pace activities, rest between tasks, sit instead of stand when possible, and use tools like rolling backpacks helps conserve energy. This makes daily life more manageable and reduces frustration.LWW Journals+1

14. School and work accommodations
Teachers and employers can provide adjustments such as extra time to walk between rooms, permission to use elevators, ergonomic chairs, and flexible schedules. These accommodations reduce physical stress and support academic or job success while respecting the person’s health limits.Muscular Dystrophy Association+1

15. Psychological counseling and mental health support
Living with a chronic genetic disease can cause sadness, anxiety, or low self-esteem. Counseling, cognitive-behavioral therapy, or support from a psychologist helps people process emotions, build coping skills, and stay motivated with long-term therapy plans. Good mental health improves overall quality of life.Springer+1

16. Peer support and patient groups
Joining CMT support groups, either in person or online, helps people feel less alone. They can share practical tips, learn about new research, and get emotional encouragement from others with similar challenges. Patient organizations often provide education materials and guides for therapists who do not know CMT well.Charcot-Marie-Tooth Association+1

17. Genetic counseling for families
Because CMT from PLEKHG5 mutation is inherited, genetic counselors can explain how the condition runs in families, the chances of passing it to children, and possible testing options. This helps families make informed reproductive and life choices and reduces fear of the unknown.Springer+1

18. Respiratory and speech therapy when needed
In rare severe cases where nerves to breathing or swallowing muscles are affected, respiratory or speech therapists may be involved. They can teach breathing exercises, safe swallowing techniques, and strategies to prevent aspiration. The aim is to protect lung health and keep eating and speaking as safe and clear as possible.PMC+1

19. Pain self-management techniques
Non-drug pain strategies such as heat packs, relaxation exercises, gentle massage, and mindfulness can support medical treatment. These methods help calm the nervous system and reduce the emotional burden of chronic pain, which often increases the perception of physical pain.Springer+1

20. Long-term rehabilitation programs
Research shows that intensive, structured rehabilitation programs combining physiotherapy, balance training, and endurance exercise can improve function in CMT, even though they do not cure the disease. Long-term follow-up is needed because CMT is progressive, and therapy plans must adapt over time.Springer+1

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Drug Treatments

Important: No medicine can cure Charcot-Marie-Tooth disease caused by PLEKHG5 mutation. Drugs are used mainly to treat neuropathic pain, muscle cramps, mood problems, and sleep issues. Doses below are typical examples from adult studies; your own dose must always be decided by your doctor.PMC+1

1. Gabapentin (Neurontin and related products)
Gabapentin is an anti-seizure medicine widely used for neuropathic pain. FDA-approved labels describe doses up to 1,800–3,600 mg per day in divided doses for neuropathic pain like post-herpetic neuralgia; similar ranges are often used off-label for CMT-related pain. It reduces abnormal firing in damaged nerves, lowering burning and shooting pain. Common side effects are sleepiness, dizziness, and weight gain.FDA Access Data+2FDA Access Data+2

2. Pregabalin (Lyrica, Lyrica CR)
Pregabalin is closely related to gabapentin and is FDA-approved for several neuropathic pain conditions. Typical starting doses are about 150 mg per day divided into two or three doses, with increases up to 300–600 mg per day if needed and tolerated. It binds to calcium channels in nerve cells and reduces the release of pain-signaling chemicals. Side effects include dizziness, sleepiness, leg swelling, and weight gain.FDA Access Data+2FDA Access Data+2

3. Duloxetine (Cymbalta, Drizalma Sprinkle)
Duloxetine is a serotonin–norepinephrine reuptake inhibitor (SNRI) approved for diabetic peripheral neuropathic pain. Adults usually take 60 mg once daily; higher doses do not clearly add benefit but increase side effects. It boosts certain brain chemicals that dampen pain signals from the body. Nausea, dry mouth, sleepiness, and sweating are common side effects.FDA Access Data+4FDA Access Data+4FDA Access Data+4

4. Tricyclic antidepressants (e.g., amitriptyline)
Low-dose tricyclic antidepressants like amitriptyline are often used at night (for example, 10–25 mg at bedtime, adjusted by the doctor) to relieve neuropathic pain and improve sleep. They change how the brain and spinal cord process pain messages. Dry mouth, constipation, dizziness, and heart rhythm changes can occur, so careful medical supervision is important, especially in older adults.PMC+1

5. Other SNRIs (e.g., venlafaxine)
Venlafaxine is another SNRI sometimes used for chronic nerve pain and depression. It increases serotonin and norepinephrine, helping the nervous system filter pain. Doses vary widely and must be adjusted slowly to avoid blood pressure changes or withdrawal effects. Side effects can include nausea, increased heart rate, and insomnia.PMC+1

6. Tramadol
Tramadol is a weak opioid that also affects serotonin and norepinephrine. It may be used short-term for severe neuropathic pain that does not respond to first-line drugs, often in doses like 50–100 mg every 4–6 hours, within a maximum daily limit chosen by the doctor. There is a risk of dependence, nausea, dizziness, and seizures, so it must be used carefully.PMC+1

7. Strong opioids (e.g., oxycodone) – last resort
In very severe pain that greatly limits life and does not improve with other medicines, strong opioids may be considered for short periods under strict specialist supervision. They act on opioid receptors in the brain to reduce pain perception. However, risks include dependence, overdose, constipation, hormonal changes, and breathing problems, so guidelines recommend them only when benefits clearly outweigh risks.PMC+1

8. Topical lidocaine 5% patches
Lidocaine patches can be placed on painful skin areas, where they block sodium channels in nerve endings and reduce local pain. They are usually worn for several hours per day. Because little drug enters the bloodstream, systemic side effects are low, but skin irritation can occur. These patches are useful when pain is localized, for example on part of the foot.PMC+1

9. High-strength capsaicin creams or patches
Capsaicin from chili peppers can desensitize pain fibers when applied repeatedly to the skin. High-dose patches are applied in clinic for a set time, while lower-strength creams are used at home. The mechanism is to over-activate and then temporarily “switch off” pain receptors. It can cause burning and redness at first, so it must be used exactly as directed.ResearchGate+1

10. NSAIDs (e.g., ibuprofen, naproxen)
Non-steroidal anti-inflammatory drugs (NSAIDs) do not treat nerve damage itself, but they help with joint and muscle pain caused by abnormal walking patterns and deformities. They work by blocking enzymes that make inflammatory prostaglandins. Common side effects are stomach upset and, with long-term use, risk of ulcers or kidney problems, so they should be used at the lowest effective dose for the shortest time.Springer+1

11. Acetaminophen (paracetamol)
Acetaminophen is often used for mild to moderate musculoskeletal pain in CMT. It acts mainly in the central nervous system to reduce pain and fever, with less effect on inflammation. It is generally safer for the stomach, but high doses can cause serious liver damage, so total daily intake must never exceed recommended limits.Springer+1

12. Muscle relaxants (e.g., baclofen)
When muscle stiffness or spasms occur, medicines like baclofen can be used. Baclofen acts on GABA receptors in the spinal cord to reduce spastic muscle activity. Doses are increased slowly to avoid dizziness or weakness. These drugs must be tapered rather than stopped suddenly to prevent withdrawal symptoms.ResearchGate+1

13. Tizanidine
Tizanidine is another muscle relaxant that reduces tightness by acting on alpha-2 receptors in the central nervous system. It can cause drowsiness, dry mouth, and low blood pressure, so doctors start with low night-time doses and adjust carefully. It may help people whose abnormal posture causes secondary muscle pain.ResearchGate+1

14. Botulinum toxin injections (selected cases)
Botulinum toxin can be injected into specific overactive muscles to reduce abnormal pulling in severe deformities or painful muscle overactivity. It blocks the release of acetylcholine at the neuromuscular junction, leading to temporary relaxation. Effects last a few months, and injections may be repeated, usually as part of a broader rehabilitation plan.Ovid+1

15. Antidepressants for mood (e.g., SSRIs like sertraline)
Living with CMT can cause depression or anxiety, which in turn can worsen the experience of pain. Selective serotonin reuptake inhibitors (SSRIs) are used at standard antidepressant doses to stabilize mood. They do not directly treat nerve damage, but improving mental health often makes pain and disability easier to cope with.Springer+1

16. Sleep aids (e.g., melatonin, short-term sedatives)
Neuropathic pain and cramps can disturb sleep. Melatonin and, in selected cases, short-term sedative medicines may be prescribed. Better sleep improves daytime energy and coping ability. Because sedatives can cause dependence and falls, they are usually used for short periods and always under medical supervision.Springer+1

17. Anti-cramp agents (e.g., quinine alternatives)
Some patients experience painful night-time cramps. Doctors may try magnesium or other agents that reduce muscle excitability, along with stretching. Traditional quinine is less favored due to safety concerns. Any anti-cramp medicine should be balanced against side effects like stomach upset or heart rhythm changes.Springer+1

18. Vitamin D supplementation (if deficient)
Vitamin D is not a direct drug for CMT, but deficiency is common and can worsen muscle weakness and pain. When blood tests show low levels, doctors prescribe vitamin D at doses tailored to age and severity. Correcting deficiency supports bone strength and may indirectly improve mobility in people with CMT.Health+1

19. Vitamin B12 (if deficient)
Vitamin B12 deficiency can cause neuropathy of its own. In people with CMT and B12 deficiency, injections or high-dose tablets can improve or prevent worsening of nerve function. Doses and schedules depend on how severe the deficiency is. This therapy does not fix the genetic CMT, but it removes an extra cause of nerve damage.Premier Neurology & Wellness+1

20. Clinical-trial medicines
Some people with CMT may be offered experimental drugs in clinical trials aiming to protect nerves or correct specific genetic problems. These medicines have carefully controlled doses and strict safety rules. They should only be taken as part of official studies, not bought online or used without supervision.PMC+1

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Dietary Molecular Supplements

Evidence for supplements in Charcot-Marie-Tooth disease is limited. They may support general nerve health but do not replace medical care. Always discuss any supplement with your doctor.Healthline+1

1. Alpha-lipoic acid (ALA)
Alpha-lipoic acid is an antioxidant that helps reduce oxidative stress in cells. Studies in peripheral neuropathy suggest that doses around 600 mg per day may improve nerve pain and function, although results are mixed and not specific to CMT. ALA may protect nerve cells from damage caused by free radicals and improve blood flow. Possible side effects include stomach upset and low blood sugar in some people.Healthline+2The Foundation for Peripheral Neuropathy+2

2. B-complex vitamins (B1, B6, B12, folate)
B vitamins play key roles in nerve energy production and in maintaining the protective myelin sheath. In neuropathy, B1, B6, and B12 are often used in combination at moderate doses. When a true deficiency exists, higher therapeutic doses are given. Correcting deficiencies may reduce pain and numbness and prevent further damage. Very high B6 doses can be harmful, so dosing must follow medical advice.Premier Neurology & Wellness+1

3. Omega-3 fatty acids (fish oil)
Omega-3 fats from fish oil have anti-inflammatory properties and may support nerve membranes and blood flow. Typical supplemental doses range from 1–3 g of EPA/DHA per day, depending on cardiovascular risk and doctor guidance. They might modestly reduce pain and improve overall health, though specific data in CMT are limited. Side effects include fishy aftertaste and risk of bleeding at very high doses.Cadense+1

4. Acetyl-L-carnitine (ALC)
Acetyl-L-carnitine is involved in mitochondrial energy production and has been studied in diabetic neuropathy. Some research suggests doses of 1,500–3,000 mg per day may improve nerve function and reduce pain, but evidence is not strong for CMT specifically. Side effects can include nausea and stomach discomfort.Health+1

5. N-acetylcysteine (NAC)
NAC is an antioxidant and a source of glutathione, a key protective molecule in cells. In neuropathy research, NAC may help reduce inflammation and oxidative damage when used with other treatments. Doses in studies vary widely (for example 600–1,800 mg/day), and it can cause nausea or skin rash in some people.Health+1

6. Vitamin D
As mentioned in the drug section, vitamin D supports bone and muscle health. In people with neuropathy, low vitamin D is linked with higher pain and worse function. Supplement doses depend on blood levels, often in the range of 800–2,000 IU per day for maintenance, but higher doses may be used for correction.Health+1

7. Magnesium
Magnesium is important for muscle relaxation and nerve signaling. In some people, magnesium supplements reduce cramps and improve sleep quality. Doses typically range around 200–400 mg elemental magnesium per day, but too much can cause diarrhea or low blood pressure.Cadense+1

8. Curcumin (turmeric extract)
Curcumin is an anti-inflammatory compound found in turmeric. Studies in neuropathy suggest it may reduce inflammatory pathways and oxidative stress. Supplements often contain 500–1,000 mg per day of concentrated extracts with absorption enhancers. It is usually well tolerated but can cause digestive upset in some people.Healthline+1

9. Coenzyme Q10 (CoQ10)
CoQ10 supports mitochondrial energy production. Some small studies in nerve and muscle diseases suggest potential benefits in reducing fatigue and muscle pain, though data are limited. Typical supplemental doses range from 100–300 mg/day. It is generally safe but can interact with blood-thinning medicines.Cadense+1

10. Probiotics
Probiotics support gut health and may indirectly influence inflammation and immune balance, which can affect how the body handles chronic illness and pain. There is no direct evidence they change CMT progression, but they may improve digestive comfort and overall well-being. Strains and doses vary and should be chosen with medical advice.Health+1

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Immunity Booster and Regenerative / Stem Cell Drugs

There are no FDA-approved immune booster, regenerative, or stem cell drugs specifically for Charcot-Marie-Tooth disease caused by PLEKHG5 mutation. All such approaches are still in the research or clinical-trial stage.PMC+1

1. Gene therapy research – Scientists are studying gene-silencing or gene-replacement methods for some CMT types, but these are not yet approved treatments and dosing is only done in trials under strict rules.PMC+1

2. Neuroprotective small molecules – Various experimental drugs aim to protect nerves from degeneration or to improve myelin repair. None is yet standard care for PLEKHG5-related CMT.PMC+1

3. Stem cell transplantation – Stem cell therapies are being explored for nerve repair in many diseases, but for CMT they remain experimental. They should only be accessed through regulated clinical trials, not private unregulated clinics.PMC+1

4. Growth factor therapies – Nerve growth factors and similar molecules are being tested to see if they can support damaged nerves. At present, these are not approved for routine use in CMT.PMC+1

5. Immune-modulating drugs – Some neuropathies are autoimmune and respond to immunoglobulin or steroids, but CMT from PLEKHG5 is genetic, not autoimmune, so these medicines are not standard and are only used if another autoimmune disease is also present.PMC+1

6. Clinical-trial enrollment – The most realistic “regenerative” approach at present is to join supervised clinical trials that test new drugs or gene-based therapies. These trials have strict safety monitoring and do not guarantee benefit, but they advance knowledge for future treatments.PMC+1

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Surgeries ( Procedures and Why They Are Done)

1. Tendon transfer surgery
In cavovarus (high-arched, twisted) feet, certain tendons are re-routed to balance muscle forces and reduce foot drop. For example, tibialis posterior or toe extensor tendons may be moved to improve ankle lifting. This helps create a more stable, plantigrade (flat) foot and reduces tripping and pain.PubMed+2www.elsevier.com+2

2. Osteotomy (bone-cutting realignment)
Osteotomy means cutting and repositioning bones of the foot, such as the calcaneus (heel) or midfoot, to correct deformities like high arches. Plates or screws hold the new shape while the bone heals. The goal is to improve weight distribution, reduce pain, and allow better function with or without braces.PubMed+2ENMC+2

3. Soft-tissue release (plantar fascia and tendon lengthening)
Tight ligaments and tendons in the sole or back of the leg can be surgically lengthened or released. This increases flexibility, lets the heel touch the ground more easily, and reduces painful tension. It is often combined with tendon transfer or osteotomy in the same operation.ENMC+1

4. Toe correction (claw toe surgery)
In clawed toes, surgeons may straighten the toes by releasing tendons, removing a small piece of bone, or fusing small joints. This reduces pressure points in shoes, lowers the risk of ulcers, and makes footwear more comfortable.Charcot-Marie-Tooth Disease+1

5. Joint fusion (arthrodesis – now less common)
In very severe or rigid deformities that cannot be corrected by softer procedures, some joints may be fused in a more functional position. This reduces pain and prevents further deformity, although it also reduces movement in those joints. Modern techniques try to avoid fusion whenever possible.Charcot-Marie-Tooth Disease+1

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Prevention and Lifestyle Measures

Because CMT due to PLEKHG5 is genetic, it cannot be fully prevented, but many problems and complications can be reduced:PMC+1

1. Genetic counseling before having children to understand inheritance risks.Springer+1

2. Avoiding known nerve-toxic medicines (for example, some chemotherapy drugs like vincristine) whenever safer alternatives exist.PMC+1

3. Using proper braces and supportive footwear to prevent falls and deformities.Charcot-Marie-Tooth Association+1

4. Keeping a healthy body weight to reduce stress on weak legs and feet.Springer+1

5. Doing regular supervised physiotherapy to maintain strength and flexibility.Journal of Health and Allied Sciences NU+1

6. Checking feet daily for blisters, cuts, or pressure areas, especially if sensation is low.Charcot-Marie-Tooth Association+1

7. Preventing falls with safe home design and assistive devices as needed.Springer+1

8. Avoiding smoking and heavy alcohol use, which can further damage nerves and blood vessels.Cadense+1

9. Treating other medical problems like diabetes or vitamin deficiencies early to protect nerves.Premier Neurology & Wellness+1

10. Staying connected with CMT clinics or centers of excellence for updated care recommendations.Charcot-Marie-Tooth Association+1

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When Should Someone See a Doctor?

You should see a doctor (ideally a neurologist with experience in CMT) if you notice:

• New or worsening foot drop, frequent tripping, or difficulty climbing stairs.

• Increasing hand weakness, trouble writing, buttoning clothes, or holding objects.

• Painful foot deformities, calluses, sores, or ulcers that do not heal.

• Sudden fast changes in weakness or sensation (this is unusual in CMT and may signal another urgent problem).

• Breathing, swallowing, or severe back pain symptoms.

• Mood changes like strong sadness, anxiety, or loss of interest in daily life.

Early assessment allows better planning for braces, physiotherapy, pain control, and support at school or work.PMC+1

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What to Eat and What to Avoid

1. Eat a balanced diet rich in vegetables, fruits, whole grains, and lean proteins to support general health and muscle function.Cadense+1

2. Eat foods with healthy fats like fish (omega-3), nuts, and seeds to support nerve membranes and reduce inflammation.Healthline+1

3. Eat sufficient calcium and vitamin D (dairy or fortified foods, plus safe sun exposure) to support bones stressed by abnormal gait.The Foundation for Peripheral Neuropathy+1

4. Eat B-vitamin-rich foods such as whole grains, eggs, meat, and leafy greens to support nerve function.Premier Neurology & Wellness+1

5. Eat high-fiber foods and drink enough water to help prevent constipation, which can be worsened by pain medicines or limited mobility.Cadense+1

6. Avoid heavy alcohol intake, which can cause or worsen neuropathy and interfere with medicines.Cadense+1

7. Avoid crash diets or very low-calorie plans that lead to muscle loss and fatigue.Springer+1

8. Avoid very high doses of unproven supplements without medical supervision, as they may cause toxicity or drug interactions.Health+1

9. Avoid high-salt, high-sugar ultra-processed foods that promote obesity, diabetes, and cardiovascular disease, all of which worsen mobility.Cadense+1

10. Avoid energy drinks or high caffeine intake that may disturb sleep, which is already fragile in chronic pain conditions.Springer+1

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Frequently Asked Questions

1. Is Charcot-Marie-Tooth disease from PLEKHG5 mutation curable?
No. At present there is no cure and no approved drug that stops or reverses the nerve damage in CMT caused by PLEKHG5 mutation. Treatment focuses on reducing symptoms, preventing complications, and keeping independence with rehabilitation, braces, pain treatment, and sometimes surgery.PMC+1

2. Does everyone with this mutation become severely disabled?
No. Severity can vary widely, even within the same family. Some people have mild weakness and remain active all their life, while others may need braces or walking aids. Early therapy, careful foot care, and good general health can help keep function as good as possible.Springer+1

3. At what age do symptoms usually start?
Symptoms of PLEKHG5-related CMT often begin in childhood or teenage years, with clumsiness, frequent tripping, or difficulty running. In some people, signs appear earlier or later, depending on the exact mutation and other genetic and environmental factors.Institut de Myologie+1

4. Can exercise make the disease worse?
Gentle, supervised exercise is generally helpful and does not damage nerves. Over-exertion that causes long-lasting muscle pain or extreme fatigue is not recommended, but balanced physiotherapy, strength training, and aerobic exercise can improve function and mood.ResearchGate+1

5. Are there special shoes for CMT?
Yes. Many people benefit from supportive shoes with a firm heel, wide toe box, and custom insoles. When combined with AFOs or other braces, they can greatly improve walking and reduce pain. A podiatrist or orthotist should guide the choice.London Orthotics+1

6. Can pain always be controlled with medicines?
Many patients get good relief using neuropathic pain medicines like gabapentin, pregabalin, or duloxetine, sometimes together with antidepressants or topical treatments. However, some people may still have some pain. Combining medicines with physiotherapy, psychological support, and lifestyle changes often gives the best overall result.Springer+3FDA Access Data+3FDA Access Data+3

7. Are stem cell treatments available in clinics?
Stem cell treatments for CMT remain experimental and are not approved as standard therapy. Commercial clinics that offer expensive “cures” without strong evidence should be viewed with great caution. The safest way to access such approaches is through regulated clinical trials.PMC+1

8. Can diet alone fix CMT?
No diet can correct the underlying gene mutation. However, a healthy diet can support nerves and muscles, help control weight, and reduce the risk of other conditions that might worsen mobility or pain. Diet works together with, not instead of, medical and rehabilitation care.Cadense+1

9. Is CMT from PLEKHG5 contagious?
No. It is inherited through genes and cannot be caught from another person. Family members may share the mutation, so genetic counseling can help them understand their own risks.Springer+1

10. Can I have children if I have this type of CMT?
Yes, but there is a chance of passing on the mutation. A genetic counselor can explain inheritance patterns (often autosomal recessive) and discuss options such as partner testing or prenatal / preimplantation genetic diagnosis.Springer+1

11. Does surgery stop the disease from progressing?
No. Surgery corrects structural deformities like high arches or claw toes but does not change the underlying nerve problem. It can greatly improve walking and reduce pain, especially when combined with braces and physiotherapy.PubMed+2Charcot-Marie-Tooth Association+2

12. How often should I see my neurologist?
This depends on how fast your symptoms change. Many people benefit from regular reviews every 6–12 months to adjust braces, therapy plans, and medicines. More frequent visits may be needed after surgery or if symptoms change quickly.PMC+1

13. Can school or work life be normal with CMT?
Many people with CMT complete school, work, and lead active lives, especially when they receive early therapy, appropriate equipment, and reasonable accommodations. Honest communication with teachers or employers helps them understand and support your needs.Muscular Dystrophy Association+1

14. Do braces need to be worn forever?
Bracing needs can change over time. Some people use AFOs only during certain activities; others need them most of the day. As the disease progresses or after surgery, brace types or settings may be changed. Regular orthotist review keeps them comfortable and effective.Charcot-Marie-Tooth Association+1

15. Where can I find reliable information and support?
Trusted sources include national CMT organizations, neuromuscular clinics, and reputable hospital websites. These groups provide guidelines for therapists, information on research, and support networks for people living with Charcot-Marie-Tooth disease caused by PLEKHG5 mutation.Charcot-Marie-Tooth Association+1

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 24, 2025.