Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant Type 2M (CMT2M)

Charcot-Marie-Tooth disease, axonal, autosomal dominant type 2M (CMT2M)  is a rare, inherited nerve disease. It mainly damages the long “wires” of the peripheral nerves called axons. These nerves carry signals from the spinal cord to the muscles and bring back sensations from the skin. People with CMT2M usually develop slowly progressive weakness and thinning (wasting) of muscles in the feet and hands. Many have high-arched feet (pes cavus), weak or absent ankle reflexes, and reduced feeling in the feet and hands. CMT2M is special because, in many families, it also includes congenital droopy eyelids (ptosis) and early cataracts. The condition is passed in an autosomal dominant way, meaning a change (mutation) in a single copy of the gene can cause disease. The most common gene linked to CMT2M is DNM2 (dynamin-2), which makes a protein that helps cells pinch off and move membrane “bubbles” (vesicles) during endocytosis. Changes in DNM2 disturb this traffic system, so axons do not stay healthy. MedlinePlus+3NCBI+3Orpha+3

CMT2M is a rare, inherited nerve disease. It mainly damages the long “wires” of the peripheral nerves called axons. These nerves carry signals from the spinal cord to the muscles and bring back sensations from the skin. People with CMT2M usually develop slowly progressive weakness and thinning (wasting) of muscles in the feet and hands. Many have high-arched feet (pes cavus), weak or absent ankle reflexes, and reduced feeling in the feet and hands. CMT2M is special because, in many families, it also includes congenital droopy eyelids (ptosis) and early cataracts. The condition is passed in an autosomal dominant way, meaning a change (mutation) in a single copy of the gene can cause disease. The most common gene linked to CMT2M is DNM2 (dynamin-2), which makes a protein that helps cells pinch off and move membrane “bubbles” (vesicles) during endocytosis. Changes in DNM2 disturb this traffic system, so axons do not stay healthy. MedlinePlus+3NCBI+3Orpha+3

Doctors diagnose CMT2M based on typical symptoms and nerve tests that show an axonal neuropathy, plus genetic testing that finds a harmful DNM2 variant. The disorder usually progresses slowly over years. Some people have very mild problems; others have more limits in walking, balance, or fine hand use. Very rarely, a low white blood cell count (neutropenia) has been reported together with this condition. NCBI+1

Other names

• Autosomal dominant Charcot-Marie-Tooth disease type 2M

• CMT2M

• DNM2-related axonal CMT

• Charcot-Marie-Tooth disease, axonal, type 2M (UniProt disease tag) Orpha+1

Types

CMT2M itself is a single genetic entity, but doctors often describe clinical patterns that help with counseling and testing:

1. “Classic” CMT2M (axonal CMT with eye findings): axonal neuropathy plus congenital ptosis and early cataract in the same family. Orpha+1

2. “Pure axonal” CMT2M: axonal neuropathy from a DNM2 variant but without obvious eye findings; this has been reported in some pedigrees. ResearchGate

3. Variable-onset CMT2M: symptoms may start at birth or as late as the sixth decade; severity can range from very mild to more limiting. NCBI

4. DNM2-spectrum neuropathy: DNM2 variants can cause different CMT forms (including “intermediate” CMT type B). Which pattern appears depends on the exact mutation and where it sits in the protein. OUP Academic+1

Note: These “types” reflect clinical groupings within the same genetic disease, not separate official subtypes.

Causes

The root cause of CMT2M is a pathogenic variant in the DNM2 gene. The points below explain what that means, where variants occur, and which factors can influence how the disease looks. (Only the DNM2 variant causes the disease; other items act as modifiers of severity or expression.)

1. DNM2 (dynamin-2) pathogenic variants: A single harmful change in one DNM2 copy is enough to cause CMT2M (autosomal dominant). NCBI+1

2. Axonal vulnerability: DNM2 helps cells “pinch off” vesicles during endocytosis; defects disturb membrane traffic in long neurons, injuring axons. MedlinePlus

3. Pleckstrin-homology (PH) domain variants: Many CMT-linked DNM2 changes cluster in or near the PH domain, altering how dynamin binds membranes. ResearchGate+1

4. Gain-of-function effects: Some DNM2 mutations make the protein over-active or too stable, upsetting normal vesicle scission and axonal transport. Frontiers

5. Protein-domain specificity: Different DNM2 domains (GTPase, middle, PH) can shift disease toward neuropathy vs myopathy; CMT2M maps to neuropathy-favoring changes. Frontiers

6. Altered actin/cytoskeleton coupling: DNM2 interacts with actin; mutations can mis-organize the axonal skeleton needed for transport. Frontiers

7. Endosome/lysosome traffic defects: Disturbed vesicle sorting may impair nutrient and receptor recycling in neurons. MedlinePlus

8. Myelin-independent axonal damage: Unlike demyelinating CMT, CMT2M primarily injures the axon itself, so nerve conduction speeds are often near-normal with low amplitudes. NCBI

9. Developmental eye involvement: Some DNM2 variants also affect lens/eyelid development, explaining ptosis and early cataract in families. Orpha

10. Variable expressivity: The same DNM2 variant can look mild in one person and more severe in another, due to other genes and environment. NCBI

11. Age-dependent progression: Axons accumulate damage slowly, so weakness and numbness increase over years. NCBI

12. Length-dependent axon loss: The longest nerves are hit first, so feet are affected before hands. NCBI

13. Energy and metabolic stress: Axons with traffic defects may be more sensitive to energy shortfalls and oxidative stress (a proposed modifier). Frontiers

14. Protein “hypermultimerization”: Some mutants make DNM2 assemble abnormally, hindering normal fission activity. Frontiers

15. Compensation limits: Cells try to compensate, but not enough to protect long axons in peripheral nerves. Frontiers

16. Mutation position matters: Even nearby amino-acid changes can produce different diseases (neuropathy vs centronuclear myopathy), highlighting position-specific effects. OUP Academic+1

17. Rare hematologic association: Neutropenia has occasionally been noted alongside CMT2M, suggesting broader DNM2 roles in some families. NCBI

18. Gene dosage sensitivity: Experimental work shows that the level and activity of DNM2 are tightly balanced; too much activity is toxic to nerve/muscle. Frontiers

19. No proven lifestyle “cause”: CMT2M does not come from diet, infections, or injuries; these do not cause it, though they can affect comfort or function. NCBI

20. 50% inheritance risk: Each child of an affected parent has a 1-in-2 chance to inherit the variant. UChicago Genetic Services

Symptoms

Symptoms vary widely, even within a family.

1. Foot weakness with trouble lifting the front of the foot (foot drop) and tripping. Muscular Dystrophy Association

2. High arches (pes cavus) or hammer toes developing over time. NCBI

3. Distal muscle wasting in calves and later in hands (“inverted champagne bottle” legs). Muscular Dystrophy Association

4. Weak/absent ankle reflexes on exam. NCBI

5. Numbness or reduced feeling in feet/hands (vibration, pinprick). Muscular Dystrophy Association

6. Hand weakness causing poor grip, buttoning difficulty, or dropping objects. Muscular Dystrophy Association

7. Balance problems and unsteady walking, especially in the dark or on uneven ground. NCBI

8. Leg cramps and muscle fatigue after walking or standing. NCBI

9. Neuropathic pain or burning discomfort in the feet/hands (not in everyone). NCBI

10. Slowly progressive course over years or decades. NCBI

11. Congenital ptosis (droopy eyelids)—often present from birth in CMT2M families. Orpha

12. Early cataracts (clouding of the lens earlier than usual). Orpha

13. Frequent ankle sprains due to weakness and foot shape. NCBI

14. Cold feet or color changes from poor small-fiber function (some people). NCBI

15. Rare: easy infections if neutropenia is present in that family. NCBI

Diagnostic tests

A) Physical examination

1. Neurologic exam of strength and tone: looks for distal weakness (foot/toe/hand muscles) and muscle wasting; typical for axonal CMT. NCBI

2. Reflex testing: ankle reflexes are often reduced or absent; knee reflexes may be reduced later. NCBI

3. Sensory exam: vibration and pinprick in the feet/hands are commonly reduced. Muscular Dystrophy Association

4. Gait and balance assessment: identifies foot drop, steppage gait, and balance problems. NCBI

5. Foot/hand inspection: checks for pes cavus, hammer toes, calluses, and hand muscle wasting that suggest a long-standing neuropathy. Muscular Dystrophy Association

B) Manual bedside tests

6. Manual Muscle Testing (MMT): grades ankle dorsiflexion/plantarflexion, toe and hand intrinsic muscles to track weakness over time. NCBI

7. Romberg test: standing with feet together/eyes closed to reveal sensory ataxia from loss of position sense. NCBI

8. Heel- and toe-walking: simple way to screen distal weakness (foot drop or calf weakness). NCBI

9. Tuning fork (128 Hz): bedside check of vibration sense in toes/ankles/fingers. NCBI

10. Ten-Hole Peg or buttoning task: quick measure of fine hand dexterity affected by distal weakness. NCBI

C) Laboratory & pathological tests

11. Targeted genetic testing of DNM2: Sanger or NGS to confirm a pathogenic DNM2 variant consistent with CMT2M. Family testing clarifies inheritance. UChicago Genetic Services

12. Neuropathy gene panel (NGS): if the variant is unknown, a CMT panel (including DNM2) increases detection while checking many CMT genes at once. NCBI

13. Complete blood count (CBC): screens for neutropenia in families where this has been reported. NCBI

14. Rule-out labs: B12, TSH, HbA1c, serum protein electrophoresis—help exclude other causes of neuropathy that can coexist (not causes of CMT2M). NCBI

15. (Occasionally) nerve biopsy: rarely needed now; if done, shows axonal loss more than demyelination. Genetic testing has largely replaced biopsy. NCBI

D) Electrodiagnostic tests

16. Nerve conduction studies (NCS): in axonal CMT, conduction velocities are near-normal or mildly reduced, but amplitudes are low (axon loss). Distinguishes CMT2 from CMT1. NCBI

17. Electromyography (EMG): shows chronic denervation/reinnervation in distal muscles. Helps gauge severity and distribution. NCBI

18. Late responses (F-waves): can uncover length-dependent axonal involvement and proximal conduction issues in advanced disease. NCBI

E) Imaging & specialized exams

19. Muscle MRI (lower legs/hands): maps patterns of fatty replacement in distal muscles; useful for baseline severity and tracking. NCBI

20. Eye examination (slit lamp) ± optical coherence tomography: checks for ptosis mechanics and detects early cataracts common in CMT2M families. Orpha

Non-pharmacological treatments (therapies & others)

These improve function, safety, and comfort. They don’t change the gene but can make daily life better.

1) CMT-focused physical therapy. A plan with gentle strengthening (especially dorsiflexors and evertors), balance work, and stretching of calf/Achilles can slow contractures, improve gait, and reduce falls. Go low and slow—fatiguable muscles need rest cycles. PMC+1

2) Ankle-foot orthoses (AFOs). Carbon-fiber or hinged AFOs help foot drop, toe-clearance, and knee stability. They reduce stumbles and energy cost when walking. A certified orthotist should fit and fine-tune. PMC

3) Custom footwear & orthotics. Wide toe-box, cushioned soles, lateral support, and custom insoles off-load pressure points and improve alignment in pes cavus. PMC

4) Occupational therapy (OT). Hand weakness and sensory loss can be offset with grip-aids, pencil/utensil adaptations, button hooks, and kitchen safety training. Energy-conservation techniques help at work and home. PMC

5) Balance and falls program. Core work, proprioceptive drills, and home hazard checks (lighting, cords, rugs) reduce falls—key when ankles are weak or numb. PMC

6) Night splints or stretching casts (short term). Maintain ankle dorsiflexion range and delay fixed equinus when calves tighten. JNNP

7) Tendon-gliding and hand therapy. Preserves fine motor function and slows clawing; adaptive keyboards and voice input can help if typing is limited. PMC

8) Pain self-management. Heat/ice as tolerated, pacing, graded activity, and sleep hygiene can lower neuropathic pain intensity alongside medical options. NCBI

9) Weight management & aerobic activity. Light cycling, pool walking, or recumbent stepper protects joints and helps fatigue without overloading weak muscles. NCBI

10) Foot care education. Daily skin checks, nail care, and blister prevention are essential with sensory loss; seek care early for ulcers. NCBI

11) Mental health support. Living with a slowly progressive condition is stressful; counseling and peer groups help coping and adherence. PMC

12) Genetic counseling. Explains inheritance (50% chance to children in autosomal-dominant families), options for family planning, and updates on trials. NCBI

13) Fatigue management. Prioritize tasks, schedule rests, and consider a rollator for longer distances to conserve energy for meaningful activities. PMC

14) Workplace adjustments. Anti-fatigue mats, sit-stand options, and task redesign maintain productivity and safety. OT can write recommendations. PMC

15) Home safety adaptions. Handrails, shower chairs, and non-slip mats reduce injury risk when ankles are unstable. PMC

16) Heat-and-cold prudence. Numb areas can burn or freeze more easily; test water temperature and avoid heating pads on insensitive skin. NCBI

17) Driving assessment. Hand controls or ankle-assist devices may be needed; an OT driving program can assess safely. PMC

18) Community mobility. Trekking poles or a cane for uneven ground; choose routes with curb-cuts and elevators when possible. PMC

19) Surgical timing education. Learning when to consider tendon transfers or osteotomies helps you plan before deformities become fixed. PubMed

20) Clinical-trial awareness. Ask your neurologist about trials; although none are approved yet for CMT2M, research is active in CMT broadly. MDEdge+1

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Drug treatments

Important honesty note: There is no FDA-approved medicine for CMT2M itself. Medicines below may help symptoms like neuropathic pain, cramps, or orthostatic dizziness. Where possible, I cite the FDA label (accessdata.fda.gov) for each medicine’s approved indication (often diabetic nerve pain or post-herpetic neuralgia), and I clearly say when CMT use is off-label. Talk to your clinician about risks and interactions.

Neuropathic pain (evidence-based in other neuropathies; off-label for CMT)

1. Pregabalin (Lyrica). Helps burning, shooting pain and sleep. FDA-approved for diabetic peripheral neuropathic pain and post-herpetic neuralgia; typical CMT use is off-label. Common start 50–75 mg at night, titrating to 150–300 mg/day in divided doses if tolerated; dizziness and edema can occur. FDA Access Data+1

2. Duloxetine (Cymbalta / Drizalma Sprinkle). SNRI that reduces neuropathic pain and improves mood/sleep. FDA-approved for DPNP at 60 mg daily; nausea and somnolence are common. Off-label for CMT pain. FDA Access Data+2FDA Access Data+2

3. Gabapentin (Neurontin). Useful for neuropathic pain and sleep; titrate gradually (e.g., 300 mg nightly to 1800–3600 mg/day if needed). FDA-approved for post-herpetic neuralgia; off-label in CMT. Drowsiness and dizziness are common. FDA Access Data+1

4. Tapentadol ER (Nucynta ER). For severe, persistent neuropathic pain associated with diabetic neuropathy when opioids are necessary. Off-label in CMT; consider only if other options fail due to addiction and respiratory risks. FDA Access Data+1

5. Lidocaine 5% patch (Lidoderm/ZTlido). Numbs painful skin areas; approved for post-herpetic neuralgia; off-label for focal neuropathic pain in CMT feet. Apply to intact skin only; watch for local irritation. FDA Access Data+1

6. Capsaicin 8% patch (Qutenza). In-clinic patch for peripheral neuropathic pain (PHN and diabetic neuropathy of the feet). Off-label for CMT; can sting initially but may reduce pain for weeks. FDA Access Data

7. Tramadol (IR/ER). Weak opioid/serotonergic agent for short-term rescue when pain flares; carries dependency and serotonin-syndrome risks, especially with SNRIs/SSRIs. Use sparingly. FDA Access Data+1

8. NSAIDs (e.g., naproxen, ibuprofen). Help musculoskeletal aches from overuse, not neuropathic pain itself; use the lowest effective dose and protect the stomach/heart/kidneys as advised. FDA Access Data+1

Cramps/muscle overactivity (off-label in CMT; discuss carefully)

9. Mexiletine. An oral sodium-channel blocker; small studies suggest benefit in refractory muscle cramps. FDA-approved for ventricular arrhythmias—so CMT use is off-label; needs cardiac screening and monitoring. FDA Access Data

10. Magnesium (dietary supplement; see supplement section). Sometimes reduces nocturnal cramps; avoid excess in kidney disease (discussed below). Evidence is mixed; safe trials are reasonable. (See “supplements” below.)

Orthostatic dizziness (some people with neuropathy have this)

11. Midodrine. Alpha-1 agonist for symptomatic orthostatic hypotension; raises standing blood pressure. Take daytime doses and avoid near bedtime to reduce supine hypertension. Off-label if used in CMT-related dysautonomia. FDA Access Data+1

12. Droxidopa (Northera). A norepinephrine prodrug that can improve standing tolerance in neurogenic orthostatic hypotension; monitor for headache and hypertension. Off-label for CMT-related cases. FDA Access Data

Because there is no CMT-specific approval, most other medicines you might hear about (TCAs, venlafaxine, topical compounded agents) are off-label and should be individualized. Recent reviews reaffirm that no disease-modifying pharmacotherapy exists yet for any CMT type. PubMed+1

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Dietary molecular supplements

Supplements do not fix the gene change. They may support general nerve health or address deficiencies. Discuss interactions and lab monitoring with your clinician.

1. Vitamin D. Many adults are low. Correcting deficiency supports bone/muscle health and lowers fall risk; dose is based on blood levels (often 800–2000 IU/day maintenance after repletion). Evidence is general, not CMT-specific. NCBI

2. Vitamin B12. If low, nerve symptoms worsen. Replace per levels (oral cyanocobalamin or IM). Do not supplement blindly if already high. NCBI

3. Folate (B9). Correct documented deficiency; helps hematologic health and may indirectly support nerve function. NCBI

4. Thiamine (B1). Treat deficiency (e.g., malnutrition) to avoid superimposed axonal injury; dosing per clinician. NCBI

5. Magnesium. May help cramps in some; choose forms with fewer GI effects (glycinate). Avoid if significant kidney disease. Evidence mixed. NCBI

6. Omega-3 fatty acids. Anti-inflammatory, heart-healthy; may help generalized aches, though not proven for neuropathic pain. NCBI

7. Coenzyme Q10. Sometimes tried for fatigue; evidence is limited but safety is good in typical doses. NCBI

8. Alpha-lipoic acid. Studied in diabetic neuropathy; mixed results. Watch for hypoglycemia if on diabetes meds. NCBI

9. Acetyl-L-carnitine. Explored in neuropathy with variable results; discuss if you have thyroid disease or are on anticoagulants. NCBI

10. Multinutrient base. A standard multivitamin can prevent compounding deficits when intake is marginal; avoid mega-doses without a reason. NCBI

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Immunity-booster / regenerative / stem-cell drugs

There are no FDA-approved “immunity-booster,” regenerative, or stem-cell drugs for CMT2M. Using such products outside clinical trials can be risky or fraudulent. If you see clinics advertising “stem-cell cures” for CMT, be cautious and ask your neurologist about legitimate trials instead. Current research in CMT explores gene-level strategies (e.g., antisense, gene editing) and pathway modifiers, but these remain in studies—not approved medicines. MDEdge+1

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Surgeries (what they do and why)

1. Tendon transfer (e.g., posterior tibial transfer). Re-routes a stronger tendon to lift the foot, improving dorsiflexion and reducing trips; considered when foot drop persists despite bracing. PubMed

2. Calcaneal osteotomy. Repositions the heel bone to correct varus alignment in high-arched feet, improving weight-bearing and stability. PubMed

3. Plantar fascia release/soft-tissue balancing. Loosens tight tissues contributing to cavus and claw toes, relieving pain and pressure points. PubMed

4. Toe procedures (e.g., Weil osteotomy, interphalangeal fusion). Straighten painful claw toes that rub in shoes or ulcerate. PubMed

5. Ankle fusion (salvage). For painful, unstable end-stage deformity when other options fail; trades motion for pain relief and plantigrade position. PubMed

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Prevention tips

1. Stay active with joint-friendly exercise (pool, bike) to maintain range and stamina. NCBI

2. Protect your feet daily (inspect skin, moisturize, fix sharp nails). NCBI

3. Use the right braces/shoes to prevent falls and ulcers. PMC

4. Treat deficiencies (D, B12) early to avoid extra nerve stress. NCBI

5. Avoid known neurotoxic drugs when alternatives exist (discuss lists with your clinician; decisions are individualized). cmtausa.org

6. Keep a healthy weight to reduce joint and energy burden. NCBI

7. Vaccinate and manage infections to avoid deconditioning flares. NCBI

8. Prioritize sleep to lower pain sensitivity and fatigue. NCBI

9. Plan spaces for safety (lighting, rails, bath seats). PMC

10. Stay connected with a multidisciplinary team for timely orthotics and therapy upgrades. PMC

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When to see a doctor (red flags)

• More falls or new tripping despite braces.

• New or worsening foot ulcers, color change, or infection.

• Rapid step-change in weakness or sensation (CMT is slow; fast changes need evaluation).

• Back pain with radiating symptoms—could be a spine problem, not only CMT.

• Severe orthostatic dizziness/fainting.

• Medication side effects (sedation, swelling, mood change, constipation from opioids).

• Family planning questions (inheritance, testing). NCBI+1

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What to eat and what to avoid

Eat more: colorful vegetables and fruits, lean proteins, legumes, whole grains, nuts/seeds, and omega-3 rich foods (fish, flax). Hydrate well. This supports general nerve and muscle health, weight control, and energy. NCBI

Limit or avoid: heavy alcohol (hurts nerves), smoking (worsens circulation), ultra-processed foods, and excessive added sugars. If using NSAIDs, discuss stomach-protective strategies and avoid alcohol on dosing days. If you have neuropathic foot numbness, be careful with very hot foods or drinks near your lap to avoid burns. NCBI

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Common FAQs

1) Is CMT2M curable?
Not yet. There is no approved disease-modifying therapy; care focuses on function, safety, and symptom relief while research continues. PubMed+1

2) What gene is usually involved?
Most reported families have DNM2 variants, though phenotypes vary even within families. PMC

3) How fast does it progress?
Generally slowly over years. Many people remain mobile with the right braces and therapy. Orpha

4) Are pain medicines approved for CMT?
No. Some are FDA-approved for other neuropathic pains (like diabetic neuropathy) and used off-label for CMT symptoms. FDA Access Data+1

5) Will exercise make it worse?
Proper, low-impact exercise usually helps. Avoid over-fatiguing weak muscles; a PT can set safe targets. PMC

6) Are there risky drugs I should avoid?
Some medicines have been reported as potentially neurotoxic in CMT; decisions are case-by-case with your clinician. cmtausa.org

7) Can surgery fix my foot?
Surgery can rebalance tendons and bones to improve alignment and relieve pain, but it does not fix the nerve problem. Timing matters. PubMed

8) Should I get genetic testing?
Yes—genetic confirmation guides counseling, family planning, and may qualify you for research. Invitae

9) What about stem-cell treatments abroad?
No approved stem-cell therapy exists for CMT; be cautious of for-profit claims. Stick to regulated trials. MDEdge

10) Can orthotics really help?
Yes. The right AFO can transform gait safety and endurance. PMC

11) Why do my toes claw?
Imbalance: weaker intrinsic foot muscles and stronger toe flexors extend the PIP/DIP joints, causing clawing; therapy and surgery address this. PubMed

12) Is hand weakness part of CMT2M?
It can be. OT can provide aids and exercises to protect function. PMC

13) Are there biomarkers to track change?
Trials increasingly use functional scales and imaging/biomarkers, but standard clinic follow-up remains key. PubMed

14) Can kids be affected?
Yes. Pediatric guidelines support early therapy, bracing, and school accommodations. JNNP

15) Where can I follow research news?
Neuromuscular societies and patient groups provide updates; ask your clinician and check reputable outlets summarizing trial progress. Quest | Muscular Dystrophy Association

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: October 01, 2025.

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