Charcot-Marie-Tooth Disease (CMT)

Charcot-Marie-Tooth disease (CMT) is a group of inherited nerve diseases that slowly damage the “peripheral nerves.” These are the nerves that carry messages from the brain and spinal cord to the muscles and back from the skin to the brain. Over many years this damage makes the muscles of the feet, legs, hands, and arms weak and thin, and it can reduce feeling in these areas. CMT is one of the most common inherited nerve disorders, affecting roughly 1 in 2,500 people worldwide. MedlinePlus+2Cleveland Clinic+2

Charcot-Marie-Tooth disease (CMT) is a group of inherited nerve diseases that mainly damage the peripheral nerves in the legs, feet, hands, and arms. These nerves carry signals between the brain, spinal cord, and muscles. When they are damaged, muscles slowly become weak and thin, and feeling in the feet and hands becomes reduced or abnormal. CMT usually gets worse very slowly over many years. There is no complete cure yet, so treatment focuses on protecting nerves and muscles, reducing pain, preventing deformity, and helping people stay active and independent.Muscular Dystrophy Association+1

In CMT, the problem comes from a change (mutation) in a gene that is important for the nerve fiber or its myelin coating. Because the gene change is present from birth, the disease is lifelong. However, it usually worsens slowly, and many people live a normal life span. The severity can vary even inside the same family: some people are mildly affected, while others may have more serious disability. MedlinePlus+2Wikipedia+2

Other names

Charcot-Marie-Tooth disease has several other names used in medical books and older papers. One common name is hereditary motor and sensory neuropathy (HMSN). “Hereditary” means it runs in families, “motor” means it affects movement, and “sensory” means it affects feeling. “Neuropathy” means disease of nerves. This name is often used as an umbrella term for the whole group of CMT conditions. MedlinePlus+1

Another older name is peroneal muscular atrophy. This comes from the peroneal muscles in the lower leg, which help lift the foot. These muscles often become thin and weak early in the disease, so doctors in the past named the condition after that muscle wasting. Today, “Charcot-Marie-Tooth disease” and “HMSN” are more commonly used. Romanian J. Morphology & Embryology+1

Types of Charcot-Marie-Tooth disease

Doctors divide CMT into types based on how the nerve is damaged (the myelin insulation vs. the axon core), how it is inherited, and which gene is involved. This helps predict the course of the disease and guide genetic testing. NCBI+2Charcot-Marie-Tooth Association+2

CMT1 is a demyelinating form. The myelin sheath (the insulating cover of the nerve) is mainly damaged. Nerve conduction studies show very slow signal speed. CMT1 is usually inherited in an autosomal dominant way, meaning one changed gene from one parent is enough to cause disease. The most common subtype is CMT1A, often due to duplication of the PMP22 gene. NCBI+2JCN+2

CMT2 is an axonal form. Here, the axon (the central wire of the nerve) is mainly damaged. Nerve conduction speed is near normal, but the size of the signal (amplitude) is reduced. CMT2 is usually autosomal dominant. Important genes include MFN2, NEFL, and others involved in axon health. NCBI+2Wikipedia+2

CMT3 (Dejerine–Sottas disease) is a rare, severe, early-onset demyelinating type. Symptoms appear in infancy or early childhood and can cause marked weakness, delayed walking, and more disability than typical CMT1 or CMT2. MSD Manuals+1

CMT4 is usually autosomal recessive (both copies of the gene are changed). It often starts in childhood and can be more severe. Many different genes are involved, such as GDAP1 and NDRG1, which affect myelin or Schwann cell function. www.elsevier.com+1

CMTX occurs when the faulty gene is on the X chromosome (often GJB1). Males tend to be more affected because they have only one X chromosome. Females can be mildly affected or sometimes more severely affected. Nerve conduction can show features of both demyelinating and axonal damage. Wikipedia+2Orpha+2

There are also intermediate forms (dominant intermediate CMT), where nerve tests show findings between classic demyelinating and axonal patterns. As genetics advances, more subtypes are being discovered and named. NCBI+1

Causes

All causes of CMT are genetic. Below are 20 important genetic or biological causes, written in simple language.

1. PMP22 gene duplication (CMT1A)
   The most common cause of CMT is having an extra copy (duplication) of a gene called PMP22. This gene makes a protein in myelin. Too much PMP22 leads to unstable myelin, so nerve signals slow down. This causes weakness and loss of feeling, especially in the feet and legs. JCN+1

2. PMP22 deletion or point mutation
   Some people have a missing piece or small change inside the PMP22 gene instead of an extra copy. These changes can also disturb myelin. They may cause CMT or related conditions like hereditary neuropathy with liability to pressure palsies, depending on the exact change. JCN+1

3. MPZ (myelin protein zero) gene mutations
   The MPZ gene makes a key protein that helps myelin layers stick together. When this gene is faulty, myelin becomes abnormal, leading to demyelinating or sometimes axonal neuropathy. Symptoms can start in childhood or adulthood and vary in severity. Wikipedia+2www.elsevier.com+2

4. GJB1 (connexin 32) gene mutations – CMTX1
   The GJB1 gene provides instructions for a channel protein (connexin 32) in Schwann cells. This channel helps cells communicate. When it is mutated, the communication fails, myelin becomes damaged, and nerves in both the peripheral and sometimes central nervous system are affected, causing X-linked CMT. Wikipedia+2Orpha+2

5. MFN2 gene mutations (CMT2A)
   MFN2 helps control mitochondria, the “power stations” of cells, and the shape of nerve axons. Changes in MFN2 cause axonal damage, especially in long nerves to the feet and legs. This leads to early-onset weakness and balance problems in many people with CMT2A. Wikipedia+2www.elsevier.com+2

6. GDAP1 gene mutations
   GDAP1 is involved in mitochondrial function and cell survival. Mutations can cause both demyelinating (CMT4) and axonal forms of CMT. In recessive cases, symptoms often begin in childhood and may be more severe, with significant foot deformities and walking difficulty. www.elsevier.com+1

7. NEFL (neurofilament light chain) gene mutations
   NEFL helps build the internal skeleton of nerve fibers. When this structure is abnormal, axons are fragile and signals weaken. NEFL mutations cause certain CMT2 subtypes, often with distal weakness, sensory loss, and reduced nerve signal amplitudes. Wikipedia+2PMC+2

8. PRX (periaxin) gene mutations
   Periaxin helps Schwann cells maintain stable myelin. Mutations lead to severe demyelinating neuropathy, often classified as CMT4F. Children may have delayed walking, marked weakness, and sensory loss because myelin never forms normally. Wikipedia+2www.elsevier.com+2

9. SH3TC2 gene mutations
   SH3TC2 mutations usually cause a recessive demyelinating CMT (often in specific ethnic groups). The protein is involved in Schwann cell function. Damage leads to very slow nerve conduction and early foot deformities, sometimes with spinal root or cranial nerve involvement. PMC+2www.elsevier.com+2

10. NDRG1 gene mutations
    NDRG1 is important for Schwann cell and myelin health. Recessive mutations, especially in some populations, cause CMT4D. People often develop hearing loss along with the typical neuropathy signs, showing how one mutated gene can affect multiple systems. www.elsevier.com+1

11. HSPB1 and HSPB8 gene mutations
    These genes code for small “heat-shock” proteins that protect cells from stress. Mutations can lead to CMT2 or related motor neuropathies by making axons more vulnerable to damage and causing gradual distal weakness and muscle wasting. PMC+1

12. GARS1 (glycyl-tRNA synthetase) gene mutations
    GARS1 mutations cause an axonal neuropathy often classified as CMT2D or a distal hereditary motor neuropathy. The protein is needed for normal protein building in cells. When it is abnormal, long motor axons slowly fail, giving weakness, especially in the hands and feet. Wikipedia+2PMC+2

13. FIG4 gene mutations
    FIG4 helps regulate membranes in cells, including nerves. Mutations can cause CMT type 4J and other neuropathies. This leads to problems with axonal survival and myelin structure, with progressive distal weakness and sensory loss. PMC+1

14. FGD4 (FRABIN) gene mutations
    FGD4 is involved in signaling pathways in Schwann cells. Recessive mutations cause CMT4H, a demyelinating neuropathy with early-onset weakness, foot deformities, and scoliosis in some patients. ivami.com+1

15. LITAF and LRSAM1 gene mutations
    These genes are linked to pathways that handle cellular waste and protein recycling. When they are mutated, abnormal proteins build up in Schwann cells, disrupting myelin and leading to slowly progressive neuropathy. PMC+1

16. Mitochondrial DNA variants (e.g., mt-tRNA genes)
    Some families have CMT caused by mutations in mitochondrial tRNA genes. Mitochondria have their own DNA, passed mainly from the mother. When these genes are faulty, energy supply to long nerves is poor, leading to weakness, pain, and sensory loss in the limbs. Frontiers+1

17. SORD deficiency and related metabolic defects
    Newer research has found that lack of the enzyme sorbitol dehydrogenase (SORD) can cause a treatable hereditary neuropathy similar to CMT2. High sorbitol levels can damage nerves. This shows that metabolic pathways, not only myelin genes, can cause CMT-like disease. ResearchGate+1

18. Unknown or yet-unidentified gene mutations
    In some patients, the clinical picture and nerve tests clearly show CMT, but genetic tests do not find a mutation. This means there are still undiscovered genes or complex gene interactions that can cause the disease. Research continues to identify these. Dove Medical Press+2ehsj.skums.ac.ir+2

19. De novo (new) mutations
    Sometimes a person develops CMT even though neither parent has signs of the disease. In these cases, a new gene change appears in the egg or sperm cell. The person can still pass the altered gene to their children, turning a “new” mutation into a family trait. MedlinePlus+1

20. Combined genetic and modifier effects
    Some people carry a common CMT gene mutation but have milder or more severe disease than expected. Other genes, called “modifier genes,” and environmental factors such as overall health may change how strongly the main mutation shows itself. This interaction is still being studied. Dove Medical Press+2ResearchGate+2

Symptoms

1. Distal muscle weakness in feet and legs
   One of the earliest symptoms is weakness of the small muscles in the feet and lower legs. People may notice that they cannot lift their foot properly or feel that their ankles are “floppy.” This happens because the longest nerves are affected first, so muscles farthest from the spine weaken earlier. Mayo Clinic+2Romanian J. Morphology & Embryology+2

2. Foot drop and tripping
   Because the muscles that lift the front of the foot are weak, the toes may drag on the ground when walking. This is called “foot drop.” People often trip over small bumps or need to lift their knees higher with a “steppage gait” to clear the toes. PFM Journal+2Muscular Dystrophy Association+2

3. High-arched feet (pes cavus)
   Many people with CMT develop very high arches and sometimes an inward-turned heel (cavovarus foot). These fixed deformities reflect long-term muscle imbalance: some muscles become weak, while others stay relatively strong and pull the bones into abnormal positions. Muscular Dystrophy Association+2PMC+2

4. Hammertoes or claw toes
   The small muscles in the feet that normally stabilize the toes become weak, while stronger muscles pull the toes down. This makes the toes bend like a hammer or claw. These deformities can make shoe fitting difficult and may cause calluses or pain. PMC+2mansapublishers.com+2

5. Lower leg muscle wasting (“stork legs”)
   Over time, the muscles below the knee shrink because the nerve supply is poor. The lower legs may look thin compared with the thighs, sometimes described as “inverted champagne bottle” or “stork-like” legs. This is a visible sign of chronic neuropathy. Romanian J. Morphology & Embryology+2PFM Journal+2

6. Reduced or absent ankle reflexes
   When a healthcare professional taps the Achilles tendon, the usual reflex kick may be weak or absent. This happens because the reflex arc depends on healthy sensory and motor fibers, which are damaged in CMT. Reflex loss is a common examination finding. ResearchGate+2Romanian J. Morphology & Embryology+2

7. Numbness and reduced touch sensation
   People often feel numbness, tingling, or “pins and needles” in their toes and feet. Over years, they may have trouble feeling light touch, pain, or temperature. This sensory loss can travel upward toward the knees and later affect the hands. Mayo Clinic+2MedlinePlus+2

8. Loss of vibration and joint position sense
   Many patients lose the ability to sense vibration (tested with a tuning fork) and to know where their joints are in space (proprioception). This makes it hard to walk in the dark or on uneven ground because the brain gets less feedback from the feet. Romanian J. Morphology & Embryology+2PFM Journal+2

9. Balance problems and unsteady gait
   Weakness, foot deformities, and sensory loss together cause poor balance. People may sway when standing, especially with eyes closed, and may walk with a wide-based or high-stepping gait to feel more stable. Falls and sprained ankles may occur. PFM Journal+2Wiley Online Library+2

10. Hand weakness and poor fine movements
    As the disease advances, the hands can be affected. People may find it hard to do fine tasks like buttoning clothes, writing, or opening jars. The small hand muscles may waste, and the fingers may look thinner. Mayo Clinic+2PFM Journal+2

11. Hand and foot cramps or spasms
    Some individuals experience painful cramps or spasms in the feet, calves, or hands. These can be triggered by overuse or at night. They are thought to reflect unstable nerve signals and over-excitable muscle fibers. Frontiers+2Romanian J. Morphology & Embryology+2

12. Neuropathic pain or burning sensations
    Not everyone has pain, but some feel burning, shooting, or electric-shock-like pains in the feet and legs. This “neuropathic pain” comes from injured sensory nerves sending faulty signals to the brain. It can disturb sleep and daily activities. Mayo Clinic+2Muscular Dystrophy Association+2

13. Fatigue and reduced endurance
    Because muscles are weak and nerve signals are less efficient, walking even short distances can feel tiring. People may need to rest more often and may have trouble keeping up with peers, especially during sports or physical work. Dove Medical Press+2ehsj.skums.ac.ir+2

14. Scoliosis or hip and knee deformities
    Some patients, especially those with early-onset forms, develop curvature of the spine (scoliosis) or problems with hip and knee alignment. These result from long-term muscle imbalance and can further affect walking and posture. Orthobullets+2Wiley Online Library+2

15. Breathing or swallowing problems (rare)
    In a few severe cases, nerves supplying the diaphragm or throat muscles can be affected. This may lead to snoring, shortness of breath when lying down, or choking on food. These complications are uncommon but show that CMT can sometimes affect more than the limbs. Dove Medical Press+2The Sun+2

Diagnostic test

Physical exam tests

1. General neurological examination
   A neurologist first takes a detailed history and performs a full exam of strength, sensation, reflexes, and gait. They look for the typical pattern: distal weakness, sensory loss in a stocking-and-glove pattern, reduced ankle reflexes, and foot deformities. The pattern helps distinguish CMT from other nerve diseases. Romanian J. Morphology & Embryology+2Orthobullets+2

2. Gait observation and walking assessment
   The doctor watches how the person walks, turns, and runs if possible. They look for foot drop, steppage gait, frequent tripping, or a wide-based gait. Walking on heels, toes, and in a straight line can reveal subtle weakness and balance problems typical of CMT. PFM Journal+2Orthobullets+2

3. Inspection of feet and legs
   The examiner inspects the shape of the feet for high arches, hammertoes, or flat feet, and looks for calluses or pressure sores. They also note muscle wasting in the calves and shins. These visible signs, together with family history, strongly suggest a hereditary neuropathy. Muscular Dystrophy Association+2PMC+2

4. Reflex testing
   Using a reflex hammer, the doctor taps various tendons, especially the Achilles. In CMT, ankle reflexes are often lost early, and knee reflexes may be reduced later. Reflex patterns help separate CMT from conditions that mainly affect the brain or spinal cord. ResearchGate+2Romanian J. Morphology & Embryology+2

5. Sensory examination
   Light touch, pinprick, vibration, and joint position sense are tested on the toes, feet, and hands. In CMT, vibration and position sense are often reduced, and there may be numbness to light touch or pinprick. The distribution helps confirm a length-dependent peripheral neuropathy. Romanian J. Morphology & Embryology+2MedlinePlus+2

Manual and bedside functional tests

6. Manual muscle testing (MMT)
   The examiner asks the patient to move each joint against resistance, grading strength on a standard scale. Weakness is usually worse in ankle dorsiflexion (lifting the foot) and toe extension. MMT tracks progression over time and guides therapy such as braces or physiotherapy. Orthobullets+2ClinMed Journals+2

7. Romberg test for balance
   The patient stands with feet together, first with eyes open and then closed. In CMT, balance may worsen with eyes closed because the body relies more on visual cues when proprioception from the feet is poor. This simple test shows sensory ataxia from neuropathy. Romanian J. Morphology & Embryology+2PFM Journal+2

8. Heel, toe, and tandem walking tests
   Walking on heels tests dorsiflexor strength, walking on toes tests plantar-flexors, and walking heel-to-toe in a line stresses balance. Difficulty with these tasks is common in CMT and helps distinguish neuropathic weakness from other causes. Orthobullets+2PFM Journal+2

9. Timed functional tests (e.g., timed 10-meter walk)
   Short timed walking tests or timed hand tasks (like buttoning) are simple ways to measure mobility and hand function. They help monitor disease course and the effect of braces, surgery, or rehabilitation over the years. ClinMed Journals+2PFM Journal+2

Lab and pathological tests

10. Basic blood tests to rule out other neuropathies
    Blood tests for blood sugar, vitamin B12, thyroid hormones, kidney and liver function are often done. These help exclude non-genetic causes of neuropathy, such as diabetes or vitamin deficiency, which can look similar to CMT but are treated differently. NCBI+2ClinMed Journals+2

11. Targeted genetic blood tests (PMP22 and common genes)
    Once CMT is suspected from exam and nerve tests, blood is taken for genetic testing. Many labs first look for PMP22 duplication or deletion and mutations in common genes like GJB1, MPZ, and MFN2, which together explain a large share of cases. Mayo Clinic Laboratories+3ltd.aruplab.com+3SAGE Journals+3

12. Expanded next-generation sequencing panels
    If first-line tests are negative, broader gene panels or whole-exome sequencing may be used to search dozens of CMT-related genes at once. This approach has greatly increased the chance of finding the exact genetic cause in recent years. PMC+2Dove Medical Press+2

13. Nerve biopsy (rarely needed now)
    In a nerve biopsy, a small piece of a sensory nerve (often at the ankle) is surgically removed and examined under a microscope. Today it is used less often for CMT because genetic testing and nerve conduction studies usually give enough information, but it can help in difficult cases. Nature+3Mayo Clinic+3Muscular Dystrophy Association+3

14. Cerebrospinal fluid (CSF) analysis (selected cases)
    A lumbar puncture to test CSF is not routine for CMT but may be done when doctors need to rule out inflammatory neuropathies like CIDP. These conditions can sometimes mimic CMT but usually show higher protein levels in the CSF and respond to immune treatments. NCBI+2PMC+2

Electrodiagnostic tests

15. Nerve conduction studies (NCS/NCV)
    Nerve conduction studies measure how fast and how strongly electrical signals travel along nerves. In CMT1, conduction is very slow, showing demyelination; in CMT2, speed is near normal but responses are small, showing axonal loss. Guidelines recommend NCS in all suspected CMT cases. Charcot-Marie-Tooth Association+4NCBI+4www.elsevier.com+4

16. Electromyography (EMG)
    With EMG, a fine needle electrode is placed into muscles to record their electrical activity. In CMT, EMG may show chronic denervation and reinnervation changes. Together with NCS, EMG helps confirm a peripheral neuropathy and distinguish CMT from muscle diseases or spinal cord problems. NCBI+2Medscape+2

17. F-wave and late response studies
    F-waves are late responses generated when an electrical impulse travels up the motor nerve to the spinal cord and back. In CMT, F-waves can be prolonged or absent, reflecting diffuse motor nerve involvement. These measures give extra detail about the extent of neuropathy. www.elsevier.com+2ClinMed Journals+2

18. Somatosensory evoked potentials (SSEPs)
    SSEPs measure how sensory signals travel from the limbs through the spinal cord to the brain. They are not needed in every case but can show slowed or reduced responses in long-standing CMT, giving a broader view of sensory pathway function. Romanian J. Morphology & Embryology+2ClinMed Journals+2

Imaging tests

19. X-rays of the feet and spine
    Plain X-rays help show bone deformities such as high arches, claw toes, flat feet, or scoliosis. They do not show nerve damage but are useful for planning braces or orthopedic surgery and for tracking structural changes over time. PMC+2Orthobullets+2

20. MRI or ultrasound of nerves and muscles
    Magnetic resonance imaging (MRI) or ultrasound can show thickened nerves and muscle wasting. These scans are not required for diagnosis in every patient but can help in complex cases, research, or surgical planning. They may also help exclude other causes of nerve or muscle problems. Sequencing+2ClinMed Journals+2

Non-Pharmacological Treatments

1. Physical therapy
   Physical therapy is one of the most important treatments for Charcot-Marie-Tooth disease. A trained therapist teaches gentle stretching, strengthening, balance, and walking exercises. The main purpose is to keep muscles as strong and flexible as possible and to prevent contractures and joint stiffness. The main mechanism is regular, low-impact movement that stimulates muscles and nerves without overworking them, helping to slow down loss of strength and to keep daily activities easier.Physiopedia+1

2. Occupational therapy
   Occupational therapy focuses on daily tasks such as dressing, cooking, writing, and computer use. The purpose is to help people with weak hands or feet stay independent at home, school, or work. The therapist may teach energy-saving methods, joint-protecting positions, and ways to organize the house. The mechanism is to match tasks and tools to the person’s abilities, reducing strain on weak muscles and preventing overuse injuries.

3. Ankle-foot orthoses (AFOs)
   AFOs are custom plastic or carbon-fiber braces that support the ankle and foot. The purpose is to control foot drop, improve balance, and reduce the risk of tripping and falling. They work by holding the ankle in a more stable and lifted position during walking, which keeps the toes from dragging and allows a smoother, safer step.Charcot-Marie-Tooth Association+1

4. Special footwear and insoles
   Supportive shoes, cushioned insoles, and custom foot orthoses are often needed in CMT. The purpose is to support high arches or flat feet, reduce pressure points, and improve walking comfort. The mechanism is better weight distribution across the foot and more stable contact with the ground, which can reduce pain, calluses, and falls.

5. Hand splints and wrist supports
   Some people develop weakness in the hands and fingers. Hand splints or wrist braces keep joints in good alignment. The purpose is to make gripping and pinch activities easier and to prevent deformities of fingers and wrists. The mechanism is external support for weak muscles, which reduces stress on small joints and tendons.

6. Stretching programs
   Regular stretching of calves, hamstrings, and foot muscles is very important. The purpose is to prevent contractures that can cause fixed deformities, such as tight Achilles tendons or bent toes. The mechanism is gentle, repeated lengthening of muscles and tendons, which helps them stay longer and more flexible over time.

7. Strengthening exercises
   Carefully planned strengthening exercises focus on muscles that are not yet very weak, such as hips, thighs, and core muscles. The purpose is to support the joints of the legs and feet and to keep walking safer. The mechanism is progressive resistance training at low to moderate intensity, which builds muscle fibers and improves endurance without causing damage.

8. Balance and coordination training
   Because sensory loss and muscle weakness can disturb balance, special exercises (standing on foam, stepping over obstacles, using a wobble board) are used. The purpose is to reduce falls and improve confidence when walking on uneven ground. The mechanism is repeated training of the brain, eyes, inner ear, and remaining sensory nerves to work together more effectively.

9. Gait training
   Physical therapists may teach specific walking techniques, such as lifting the knee more, using a heel-to-toe pattern, or using assistive devices. The purpose is to make walking smoother, safer, and less tiring. The mechanism is repetition of correct movement patterns until they become a habit, reducing abnormal compensations that strain hips, knees, and back.

10. Use of canes, crutches, or walkers
    Some people with CMT benefit from walking aids. The purpose is to provide extra support and prevent falls when weakness or balance problems become stronger. The mechanism is shifting part of the body weight to the arms and the device, which lowers demands on weak leg muscles and improves stability.

11. Podiatry care
    Regular visits to a podiatrist (foot doctor) help manage calluses, pressure points, and nail problems. The purpose is to prevent ulcers and infections in feet with reduced feeling. The mechanism is early detection and treatment of skin and nail issues and advice on proper footwear and foot hygiene.

12. Pain psychology and coping skills
    Chronic neuropathic pain and fatigue can be stressful and depressing. Working with a psychologist or counselor trained in pain management teaches relaxation, breathing, distraction, and acceptance strategies. The purpose is to reduce the emotional suffering linked to pain and disability. The mechanism is changing how the brain interprets pain signals and stress, which can lower perceived pain intensity.

13. Aquatic therapy
    Exercise in warm water can be very helpful. The water holds part of the body weight, making movement easier for weak muscles. The purpose is to safely improve strength, flexibility, and cardiovascular fitness. The mechanism is buoyancy and gentle water resistance, which reduce joint impact while still providing enough load to train muscles.

14. Low-impact aerobic exercise
    Activities such as stationary cycling, walking on flat ground, or gentle swimming are usually recommended. The purpose is to improve heart and lung fitness, reduce fatigue, and support weight management. The mechanism is repeated moderate activity that increases blood flow to muscles and nerves, helping them use oxygen more efficiently.

15. Weight management and nutrition counseling
    Extra weight can make walking and balance much harder in people with CMT. A dietitian can help design a healthy eating plan that fits cultural and personal preferences. The purpose is to reach or keep a healthy body weight. The mechanism is balancing calories, nutrients, and activity to prevent overweight, which reduces load on weak muscles and joints.

16. Home and school/work modifications
    Simple changes such as grab bars, ramps, non-slip mats, and adapted desks can make life safer. The purpose is to reduce falls, injuries, and fatigue during daily activities. The mechanism is removing physical barriers and awkward movements so that weak muscles do not have to work harder than necessary.

17. Assistive hand devices
    Tools like built-up pens, jar openers, button hooks, and adapted keyboards can help weak hands. The purpose is to keep independence in writing, eating, and dressing. The mechanism is enlarging handles and changing leverage so that less grip force is needed to do the same task.

18. Education and genetic counseling
    Because CMT is inherited, families benefit from learning how it is passed on and what testing options exist. The purpose is to support informed choices about family planning and early diagnosis. The mechanism is sharing clear, accurate information about genes, testing methods, and the meaning of results.hnf-cure.org+1

19. Support groups and patient communities
    Joining CMT support groups, online or in person, connects people and families who share similar problems. The purpose is emotional support, practical tips, and reduced feelings of isolation. The mechanism is peer-to-peer learning and encouragement, which improves coping and mental health.

20. Fall prevention training
    Targeted training teaches how to move safely in bathrooms, stairs, crowded places, or at night. The purpose is to reduce the number and severity of falls. The mechanism is building habits such as using rails, clearing clutter, wearing stable shoes, and moving more slowly in risky situations.

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Drug Treatments

Note: There is currently no FDA-approved drug that cures CMT itself. Most medicines treat symptoms such as neuropathic pain, cramps, or mood changes. Doses below are typical adult ranges from FDA labels or standard guidelines for neuropathic pain, not personal advice.Muscular Dystrophy Association+2Charcot-Marie-Tooth Association+2

1. Gabapentin (Neurontin and similar)
   Gabapentin is an anticonvulsant widely used for neuropathic pain. For adults with nerve pain, doses often start around 300 mg per day and are slowly increased, commonly up to 1800 mg/day in divided doses, based on response and tolerance. The purpose is to reduce burning, shooting, or electric-like pain. The mechanism is binding to calcium channels in nerve cells, which reduces the release of pain-related chemicals. Common side effects include dizziness, sleepiness, and swelling of legs.FDA Access Data+1

2. Pregabalin
   Pregabalin is similar to gabapentin but has more predictable absorption. It is usually given two or three times a day, with total daily doses often between 150–600 mg, adjusted by the doctor. The purpose is relief of neuropathic pain and improvement of sleep. The mechanism is modulation of calcium channels, lowering abnormal nerve firing. Side effects can include dizziness, weight gain, and blurred vision.

3. Duloxetine (Cymbalta, Drizalma Sprinkle)
   Duloxetine is an SNRI antidepressant approved for diabetic peripheral neuropathic pain, and often used off-label for other neuropathic pains. A common dose is 60 mg once daily for adults, sometimes started at 30 mg for a week to improve tolerance. The purpose is to reduce pain and also help low mood or anxiety. The mechanism is increasing serotonin and norepinephrine levels in the brain and spinal cord, which modulate pain pathways. Side effects include nausea, dry mouth, and sleep changes.FDA Access Data+1

4. Amitriptyline
   Amitriptyline is a tricyclic antidepressant used in low doses for neuropathic pain, often 10–75 mg at night depending on tolerance. The purpose is pain relief and improved sleep quality. The mechanism is blocking reuptake of serotonin and norepinephrine and affecting certain ion channels, which reduce pain signal transmission. Side effects include dry mouth, constipation, and drowsiness, so it must be used carefully, especially in older adults.PMC+1

5. Nortriptyline
   Nortriptyline is related to amitriptyline but often better tolerated. Doses usually start low, such as 10–25 mg at night, and are slowly increased. The purpose is treatment of neuropathic pain with fewer sedating effects than amitriptyline. The mechanism is similar modulation of serotonin and norepinephrine, with some sodium channel effects. Side effects include dry mouth, constipation, and possible heart rhythm changes at higher doses.

6. Venlafaxine
   Venlafaxine is another SNRI sometimes used when duloxetine is not suitable. Doses for neuropathic pain are often in the range of 75–225 mg per day, guided by the doctor. The purpose is to reduce nerve pain and treat associated depression or anxiety. The mechanism is boosting serotonin and norepinephrine in central pain pathways. Side effects can include increased blood pressure, nausea, and sweating.

7. Tramadol
   Tramadol is a weak opioid with additional effects on serotonin and norepinephrine. It may be used for acute flare-ups of neuropathic pain when first-line drugs are insufficient. Doses and schedules vary, but doctors usually use the lowest effective dose for the shortest time because of dependence and side effect risks. Mechanism includes mild opioid receptor activation and reuptake inhibition of serotonin and norepinephrine. Side effects include nausea, dizziness, and risk of addiction.

8. Topical lidocaine (patches or creams)
   Lidocaine 5% patches or gels can be used for localized burning pain or allodynia (pain from light touch). They are applied to painful skin areas for limited hours each day, following product instructions. The purpose is local pain control without major whole-body side effects. The mechanism is blocking sodium channels in small nerves in the skin, stopping pain signals before they reach the brain. Side effects are usually mild skin irritation.Springer Link+1

9. Topical capsaicin
   Capsaicin creams or high-strength patches are sometimes used for localized neuropathic pain. They must be applied exactly as recommended, sometimes in a clinic for stronger patches. The purpose is long-lasting reduction of local pain. The mechanism is overstimulation and later depletion of substance P and other pain transmitters in skin nerves, making them less responsive. Side effects include burning or stinging at the application site.

10. Nonsteroidal anti-inflammatory drugs (NSAIDs)
    Drugs like ibuprofen or naproxen may help with musculoskeletal pain from overworked joints and muscles, though they often do not control nerve pain itself. Doses follow standard over-the-counter or prescription guidance. The purpose is relief of aching, inflammation, and soreness after activity. The mechanism is inhibition of COX enzymes and prostaglandin production. Side effects can include stomach upset, ulcers, and kidney effects with long-term use.

11. Acetaminophen (paracetamol)
    Acetaminophen can be used for mild pain and to reduce the need for stronger medicines. Dosing must not exceed the maximum daily limit to avoid liver damage (often 3–4 g/day in adults, depending on local guidance and liver health). The mechanism is central pain modulation through several pathways that are not fully understood. Side effects are usually mild at normal doses but serious in overdose.

12. Muscle relaxants (e.g., baclofen)
    For some people with cramps or spasticity-like symptoms, baclofen may be used. Doses start low and are slowly increased, usually taken several times a day. The purpose is to reduce painful muscle contractions. The mechanism is activation of GABA-B receptors in the spinal cord, reducing excitatory signals to muscles. Side effects include drowsiness and weakness, so careful adjustment is needed.

13. Low-dose benzodiazepines (e.g., clonazepam)
    In select cases, clonazepam may be used for severe night cramps or anxiety linked to CMT. Doses must be low and carefully monitored because of dependence risk. The mechanism is enhancing GABA effects in the brain, which calms nerves and muscles. Side effects include sleepiness, memory problems, and risk of addiction, so long-term use is avoided when possible.

14. Selective serotonin reuptake inhibitors (SSRIs)
    Medicines such as sertraline or escitalopram are not primary pain drugs, but they can help treat depression and anxiety that often accompany chronic disease. The purpose is to improve mood, energy, and coping, which indirectly helps people manage pain and disability better. The mechanism is increasing serotonin activity in the brain. Side effects include stomach upset, sleep changes, and sexual side effects.

15. Alpha-lipoic acid (as a “drug-like” antioxidant in some countries)
    In some places, alpha-lipoic acid is prescribed as a drug for diabetic neuropathy; in others it is sold as a supplement. Doses often range 300–600 mg per day. The purpose is to reduce oxidative stress and improve nerve function. The mechanism is antioxidant action and possible improvement of blood flow to nerves. Side effects can include nausea and skin rash.

16. Opioid analgesics (stronger opioids)
    Stronger opioids like morphine or oxycodone are rarely needed and are usually reserved for short-term severe pain when other options fail. The purpose is strong pain relief. The mechanism is activation of opioid receptors in the brain and spinal cord to block pain signals. Side effects include constipation, sleepiness, tolerance, and high risk of dependence, so they are used with great caution.

17. Sleep aids (such as melatonin or short-course hypnotics)
    Chronic pain and discomfort can disturb sleep. Doctors may sometimes add sleep aids to improve rest. The mechanism varies by drug but usually involves calming brain activity. The purpose is better sleep, which can reduce daytime pain and fatigue. Such medicines are used at the lowest effective dose and often only for limited periods.

18. Antispasticity agents other than baclofen (e.g., tizanidine)
    If muscle tone problems are present, tizanidine may be considered. The purpose is to reduce stiffness and improve movement. The mechanism is alpha-2 adrenergic agonist activity in the central nervous system which reduces excitatory input to muscles. Side effects include low blood pressure and drowsiness.

19. Trial or research medicines like PXT3003 (in clinical trials)
    PXT3003 is an experimental oral combination (baclofen, naltrexone, sorbitol) being tested for CMT1A. It is only available in clinical trials, not routine care. The purpose is to potentially slow disease progression. The mechanism seems to involve lowering overexpression of PMP22, a key gene in CMT1A. Side effects and ideal dosing are still being studied.ClinicalTrials.gov+2NIHR Innovation Observatory+2

20. Other clinical-trial agents (gene therapies, ion-channel modulators)
    Several experimental drugs and gene therapies are in development for different CMT subtypes. They are not yet approved and are only available in research settings. Their purpose is to correct or compensate for the underlying genetic problem. Mechanisms include gene replacement, antisense oligonucleotides, or targeted ion-channel modulation. Participation in trials requires strict screening and close monitoring.Labiotech.eu

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Dietary Molecular Supplements

(Evidence for supplements in CMT is limited; they should never replace prescribed drugs or physical therapy.)

1. Alpha-lipoic acid – Often used at 300–600 mg/day, it acts as a strong antioxidant. Its functional goal is to reduce oxidative stress in nerve cells and improve nerve blood flow. The mechanism includes recycling other antioxidants like vitamin C and E and helping mitochondrial energy production.

2. Acetyl-L-carnitine – Common doses are around 500–1000 mg one to three times daily, as guided by a clinician. It supports mitochondrial energy production in nerves. The purpose is to help damaged nerves produce enough energy to function and repair. Mechanism involves transport of fatty acids into mitochondria and support of nerve regeneration pathways.

3. Coenzyme Q10 – Often taken at 100–300 mg/day. CoQ10 is part of the mitochondrial electron transport chain. Its functional goal is to support energy production and act as an antioxidant. Mechanism is improved ATP production and reduced oxidative damage within nerve cells.

4. Omega-3 fatty acids (EPA/DHA) – Fish oil or algae oil supplements are usually dosed to give around 1000 mg or more of EPA+DHA daily. The purpose is to reduce inflammation, support cell membranes, and improve cardiovascular health. Mechanism includes changing membrane lipid composition and lowering pro-inflammatory mediators.

5. Vitamin B1 (thiamine) and benfotiamine – Doses vary, often 50–300 mg/day under medical guidance. These vitamins help nerve metabolism and glucose use. The purpose is to support nerve conduction and prevent deficiency-related neuropathy. Mechanism is acting as co-factors in carbohydrate metabolism and protecting nerves from glycation damage.

6. Vitamin B6 (pyridoxine) in safe doses – Low to moderate doses (for example 25–50 mg/day) may support nerve function, but high doses can actually cause neuropathy. The purpose is to correct deficiency if present. Mechanism is co-factor roles in neurotransmitter synthesis and myelin formation.

7. Vitamin B12 (methylcobalamin) – Doses may range from oral 500–1000 mcg/day or periodic injections, depending on deficiency. It supports myelin and DNA synthesis in nerves. The purpose is to treat or prevent B12-related neuropathy, which can worsen overall nerve function. Mechanism is involvement in methylation reactions and myelin maintenance.

8. Folate (vitamin B9) – Usually 400–800 mcg/day unless a higher dose is prescribed. The purpose is to support red blood cell and nerve health and to correct deficiency. Mechanism is participation in DNA synthesis and repair, which is vital for rapidly dividing cells and nerve support cells.

9. Vitamin D – Doses depend on blood levels and local recommendations, often 600–2000 IU/day. Vitamin D supports bone strength and muscle function. The purpose is to prevent fractures and muscle weakness, which are extra problems in people with gait imbalance. Mechanism is regulation of calcium and phosphate metabolism and effects on muscle fibers.

10. Magnesium – Common doses are 200–400 mg/day, watching for kidney function and diarrhea. Magnesium helps muscle and nerve excitability. The purpose is to reduce cramps and support normal nerve signal transmission. Mechanism involves acting as a co-factor in many enzymatic reactions and stabilizing cell membranes.

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Regenerative, Immunity-Related, and Stem-Cell-Type Drugs

1. Experimental gene therapies
   Several research programs are testing gene replacement or gene silencing for specific CMT types. These are given by injections or infusions, often using viral vectors. The purpose is to correct the underlying faulty gene in nerve cells. Mechanism involves delivering a healthy copy of a gene or silencing an overactive gene. These treatments are still in trials and not routine care.Labiotech.eu

2. PXT3003 (disease-modifying candidate for CMT1A)
   As discussed above, PXT3003 is an experimental oral combination designed to lower PMP22 overexpression. The purpose is to slow or stop nerve damage progression in CMT1A. Mechanism is thought to be synergy between low-dose baclofen, naltrexone, and sorbitol that reduces toxic levels of PMP22. Dosing schedules are still under study in clinical trials.ClinicalTrials.gov+1

3. Neurotrophin or growth-factor-based therapies (experimental)
   Some research focuses on nerve growth factors or molecules that mimic them. These may be given as injections or engineered gene deliveries. The purpose is to promote regrowth of damaged nerve fibers and protect surviving ones. The mechanism is activation of specific receptors on nerve cells that trigger survival and growth pathways.

4. Mesenchymal stem-cell therapies (research setting)
   In some trials for peripheral neuropathies, mesenchymal stem cells from bone marrow or fat are injected or infused. The purpose is to provide cells that release healing factors and possibly support nerve repair. The mechanism is mainly paracrine: stem cells release anti-inflammatory and growth factors that may protect and regenerate nerves. For CMT, this is not standard and remains experimental.

5. Immunomodulatory drugs in special situations
   When there is diagnostic uncertainty between CMT and immune neuropathies, treatments like intravenous immunoglobulin (IVIG) or steroids may be tried. The purpose is to suppress auto-immune attacks on nerves. The mechanism is modulation of the immune system, but in confirmed genetic CMT they usually do not help and are not standard long-term treatments.

6. Future combination therapies
   Newer research suggests that combining gene therapy, small molecules like PXT3003, and supportive care may work better than one approach alone. The purpose is to target multiple disease pathways at once. The mechanism is multi-level action on gene expression, myelin stability, and nerve survival. These strategies are still being tested in labs and early trials.Labiotech.eu+1

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Surgeries (Procedures and Why They Are Done)

1. Foot deformity correction (osteotomies)
   Surgeons may cut and realign bones in the foot to correct high arches (pes cavus) or severe deformities. The purpose is to create a more stable, plantigrade foot that can fit in normal shoes and reduce pain. The mechanism is mechanical: changing bone shape shifts weight-bearing forces to healthier areas and improves balance.

2. Tendon transfers
   In this surgery, a stronger tendon is moved to take over the job of a weaker muscle, such as lifting the foot. The purpose is to restore active dorsiflexion and improve walking pattern. The mechanism is redirecting muscle force to compensate for paralyzed or very weak muscles, allowing more normal movement.

3. Ankle fusion (arthrodesis)
   When ankle joints are severely unstable or painful, fusion may be used. The surgeon joins the bones so the joint no longer moves. The purpose is pain relief and improved stability at the cost of some flexibility. The mechanism is eliminating painful joint motion, shifting movement demands to other joints.

4. Toe correction surgery
   Hammer toes and claw toes can be straightened by releasing tight tendons and sometimes fusing small joints. The purpose is to reduce pain, improve shoe fit, and prevent ulcers on toe tops or tips. The mechanism is changing tendon tension and joint position so toes lie flatter and share pressure better.

5. Spine surgery in rare cases
   Some people with CMT develop scoliosis or severe spine deformity. When bracing and therapy are not enough, spinal fusion surgery may be needed. The purpose is to prevent progression of the curve, reduce pain, and protect lung function. The mechanism is stabilizing the spine with rods, screws, and bone grafts.

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Preventions

1. Early diagnosis and regular follow-up – Seeing specialists early allows faster start of physical therapy, bracing, and lifestyle planning, which can prevent contractures and deformities.

2. Daily stretching and home exercises – Consistent stretching and strengthening slow stiffening and weakness, preventing fixed joint problems.

3. Using correct braces and shoes – Wearing AFOs and supportive shoes as recommended helps prevent falls, ankle sprains, and progressive foot deformities.

4. Weight control – Keeping a healthy weight lowers stress on weak feet, ankles, knees, and spine, reducing pain and injury risk.

5. Avoiding nerve-toxic medicines when possible – Some drugs (for example, certain chemotherapy agents) can worsen neuropathy; doctors try to avoid or closely monitor such drugs in people with CMT.

6. Protecting feet from injury – Checking feet daily, using safe footwear indoors and outdoors, and avoiding walking barefoot help prevent unnoticed cuts and ulcers.

7. Fall-proofing the home – Removing loose rugs, adding grab bars, and improving lighting reduce fall risk.

8. Good infection control – Treating foot infections quickly and keeping skin clean and dry helps prevent serious complications.

9. Managing other diseases (like diabetes) – Good control of blood sugar, blood pressure, and cholesterol protects nerves and blood vessels, preventing extra nerve damage.

10. Staying informed about new treatments – Keeping contact with CMT organizations and neurologists helps families learn about trials and updated guidelines, preventing missed opportunities for better care.

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When to See Doctors

You should see a doctor, ideally a neurologist familiar with peripheral neuropathies, as soon as you notice progressive weakness in the feet or hands, frequent tripping, high arches, or loss of sensation that runs in the family. Medical review is urgent if you develop rapidly worsening weakness, severe pain that does not respond to basic treatment, repeated falls, or open wounds on the feet. Sudden changes in breathing, swallowing, or heart rhythm require emergency care. Regular follow-up visits are important to adjust braces, therapy, and medicines as Charcot-Marie-Tooth disease slowly changes over time.

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What to Eat and What to Avoid

1. Eat plenty of vegetables and fruits – They supply vitamins, minerals, and antioxidants that support overall nerve and muscle health.

2. Choose lean protein – Fish, poultry, beans, and lentils provide amino acids needed for muscle repair and immune function.

3. Include healthy fats – Nuts, seeds, olive oil, and fatty fish give omega-3s that support cell membranes and may reduce inflammation.

4. Prefer whole grains – Brown rice, oats, and whole-grain breads help maintain steady energy and healthy weight.

5. Stay well-hydrated – Drinking enough water supports circulation, kidney function, and muscle performance.

6. Limit sugar and refined carbs – High sugar intake can worsen weight gain and, if diabetes occurs, nerve damage.

7. Avoid excessive alcohol – Alcohol can directly damage nerves and worsen neuropathy, so intake should be very limited or avoided.

8. Limit very salty and processed foods – Reducing salt helps protect the heart and blood vessels, which indirectly support nerve health.

9. Be careful with mega-dose supplements without medical advice – Very high doses of some vitamins, like B6, can actually damage nerves.

10. Avoid crash diets – Extreme dieting can cause nutrient deficiencies, which may further harm nerves and muscles.

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Frequently Asked Questions

1. Is Charcot-Marie-Tooth disease curable?
   At present, there is no cure for CMT. The disease is genetic, so the underlying cause cannot yet be removed. However, many people live active lives for many years with good supportive care, including physical therapy, braces, pain management, and surgery when needed.

2. Does every person with CMT end up in a wheelchair?
   No. Some people never need a wheelchair, while others may use one only for long distances or later in life. The course of CMT is very variable, even in the same family. Early therapy, braces, and fall-prevention strategies can delay or reduce the need for wheelchairs.

3. Can exercise make CMT worse?
   Gentle, well-planned exercise usually helps rather than harms. Over-exertion, especially heavy weight-lifting of very weak muscles, may cause fatigue and pain. Working with a physical therapist helps you find the right balance so exercise supports your nerves and muscles without damage.

4. Is CMT always inherited from a parent?
   Most cases are inherited, but sometimes a new (de novo) mutation appears in a child with no family history. Genetic testing can show the exact change and help with family planning decisions.

5. Do medicines for neuropathic pain treat the disease itself?
   Common pain medicines like gabapentin, pregabalin, and duloxetine reduce pain signals but do not fix the damaged nerves or genes. They are important for comfort and function but are not disease-curing treatments.

6. Are there new treatments being developed?
   Yes. Many labs and companies are working on gene therapies, small molecules like PXT3003, and other approaches that may slow or change CMT progression. These are mostly available only in clinical trials right now, but they give hope for future disease-modifying treatments.Labiotech.eu+1

7. Can diet alone treat CMT?
   Diet cannot cure CMT or reverse nerve damage, but a healthy, balanced diet can support weight control, energy levels, and overall health. This indirectly helps you move more easily and respond better to therapy.

8. Is pregnancy safe for people with CMT?
   Many people with CMT have safe pregnancies. However, pregnancy can sometimes increase symptoms like back pain and balance issues. Genetic counseling is important to discuss risks of passing CMT to children. Obstetricians and neurologists should work together for good care.

9. Can children with CMT play sports?
   Children with CMT can often join physical activities with some adaptations. Low-impact sports like swimming or cycling are usually safer than high-impact running or contact sports. Using braces and following a therapist’s advice can make participation safer.

10. Is CMT related to multiple sclerosis or ALS?
    No. CMT is a hereditary peripheral neuropathy that mainly affects peripheral nerves. Multiple sclerosis affects the central nervous system and is autoimmune, while ALS is a motor neuron disease. The symptoms may overlap (weakness, walking problems), but the causes and treatments are different.

11. Will I lose feeling completely in my feet and hands?
    Some people develop severe sensory loss, while others have only mild changes. Usually, sensation fades slowly over many years. Regular foot checks and protective footwear are important because reduced feeling increases the risk of unnoticed injuries.

12. Can CMT affect breathing or heart function?
    Most people with CMT have mainly limb symptoms, but certain rare subtypes may affect breathing muscles or heart rhythm. If you notice shortness of breath, poor sleep, or palpitations, you should see a doctor quickly for evaluation.

13. Do braces need to be worn forever?
    Braces are tools, not permanent chains. Many people use them for many years because they make walking safer and less tiring. Braces are often updated as the body and disease change. If strength improves, your therapist may adjust how often you need them.

14. Can CMT cause pain even if I feel “numb”?
    Yes. Neuropathic pain can be burning, tingling, or electric-like even in areas with reduced normal touch or temperature sensation. This happens because damaged nerves send abnormal signals to the brain. Pain medicines and non-drug strategies can help manage this.

15. What is the most important thing I can do right now?
    The most important steps are to get an accurate diagnosis, learn about your specific CMT type, begin regular physical and occupational therapy, protect your feet, and talk honestly with your doctors about pain, mood, and daily challenges. Building a long-term partnership with your care team gives you the best chance to stay mobile, independent, and confident while living with Charcot-Marie-Tooth disease.

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: December 22, 2025.