Iridogoniodysgenesis (IGDS) Caused by PITX2 Mutation

Iridogoniodysgenesis means the colored part of the eye (the iris) and the drainage angle inside the eye (iridocorneal angle or “gonio” region) did not develop normally before birth. When this happens, the iris can look thin or under-developed (iris hypoplasia), the pupil can be off-center, and the drainage angle can be malformed (goniodysgenesis). Because the drainage angle controls fluid outflow, people can develop early glaucoma (high eye pressure that can damage the optic nerve). One important genetic cause is a change (pathogenic variant) in the PITX2 gene, a master “switch” that guides eye development (and some facial, dental, and umbilical structures) in the embryo. PITX2-related iridogoniodysgenesis usually sits within the Axenfeld–Rieger spectrum of anterior segment dysgenesis disorders. NCBI+2PMC+2

Iridogoniodysgenesis is a rare eye condition present from birth. In this condition, the iris (the colored part of the eye) is under-developed (called iris hypoplasia) and the fluid-drainage angle of the eye (the gonio part) did not form normally (goniodysgenesis). Because the drain is abnormal, eye pressure can rise and damage the optic nerve, leading to glaucoma if not treated. One important genetic cause is a change (mutation) in a gene called PITX2, a “master switch” that controls how the front of the eye forms before birth. PITX2 problems can also overlap with the Axenfeld–Rieger spectrum of conditions, which share similar front-of-eye development issues and a high risk of glaucoma. Cell+3PMC+3PMC+3

PITX2 is a transcription factor—think of it as a “conductor” that turns other eye-building genes on or off at the right time. During early growth, cells called neural crest cells move into the area that becomes the front of the eye and turn into the cornea, iris stroma, drainage tissues, and part of the sclera. When PITX2 is altered, these instructions are scrambled: the iris may be thin, the drainage angle malformed, and the risk of glaucoma rises. Animal and human studies show PITX2’s key role in periocular mesenchyme, corneal endothelium/stroma specification, and drainage-tissue development. Frontiers+3PubMed+3IOVS+3

Another names

• Iridogoniodysgenesis (IGD) or Iridogoniodysgenesis anomaly (sometimes “IGDA”). These terms emphasize iris under-development and angle malformation with frequent juvenile glaucoma. PMC

• Iris hypoplasia (part of the same spectrum; iris is thin/under-developed). Arizona Genetic Eye Diseases Database

• Axenfeld–Rieger syndrome (ARS) / Axenfeld–Rieger spectrum when eye findings occur with dental, facial, or umbilical features; PITX2 is one of the main genes. NCBI+1

• Anterior segment dysgenesis (ASD) (umbrella term for developmental problems of the cornea/iris/angle). NCBI

Types

1. Isolated ocular iridogoniodysgenesis (PITX2-related): Mainly eye findings—iris hypoplasia, corectopia (off-center pupil), polycoria (multiple openings), and angle malformation—with risk of early glaucoma. PMC

2. Syndromic PITX2-related disease (Axenfeld–Rieger phenotype): The same eye findings plus systemic features such as small or missing teeth (microdontia/hypodontia), midface/maxillary hypoplasia, umbilical anomalies, and occasionally heart or hearing findings. NCBI+1

3. Overlapping ASD entities within the PITX2 spectrum: PITX2 variants can also be seen in some cases labeled iris hypoplasia, Peters anomaly, ring dermoid of the cornea, or even aniridia-like pictures—illustrating wide variability. Arizona Genetic Eye Diseases Database+1

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Causes

Because this condition is genetic, “causes” are best understood as molecular mechanisms and influences that change how eye tissues form.

1. PITX2 loss-of-function mutations (nonsense/frameshift) reduce functional protein, disturbing iris and angle development. IOVS

2. Missense mutations in the PITX2 homeodomain alter DNA binding and target-gene control during eye development. PMC

3. Splice-site variants in PITX2 can disrupt normal RNA processing and protein production. PMC

4. PITX2 microdeletions / copy-number loss remove part or all of the gene or its regulatory regions. IOVS

5. 4q25 microdeletions encompassing PITX2 cause ARS/IGD with ocular and systemic features. IOVS

6. Regulatory/enhancer defects near PITX2 lower gene expression in periocular mesenchyme (inferred from deletion and expression studies). IOVS+1

7. Neural crest–lineage PITX2 deficiency (shown in mouse models) derails development of corneal endothelium/stroma, sclera, and ocular vessels. PubMed

8. Disrupted PITX2–FOXC1 interaction (two key transcription factors) impairs anterior segment formation. PubMed+1

9. Gene-dosage sensitivity (too little or sometimes imbalance with FOXC1) modifies phenotype severity and glaucoma risk. PubMed

10. Genetic heterogeneity: different PITX2 variants → variable expressivity, even within families. PubMed

11. Downstream pathway dysregulation—abnormal control of multiple target genes guiding iris/angle morphogenesis. PMC

12. Developmental timing effects—early embryonic perturbation of anterior segment tissue migration and differentiation. NCBI

13. Left–right and craniofacial developmental roles of PITX2 can add dental/umbilical features to the eye findings. PMC

14. Modifier genes (including FOXC1 variants) can shift the phenotype toward broader ARS features or aniridia-like appearances. Taylor & Francis Online

15. Structural variants (inversions/complex rearrangements) near PITX2 that disturb gene regulation (reported within ARS cohorts). ScienceDirect

16. Somatic mosaicism (variant in some cells only) may contribute to asymmetry and variability. PubMed

17. Epigenetic changes affecting transcription-factor networks (inferred from ASD reviews). Taylor & Francis Online

18. Species-validated causality: PITX2 knockout/lineage-specific mouse models reproduce anterior segment defects, supporting causation. PubMed+1

19. Embryonic ocular blood-vessel development defects in PITX2 neural-crest models can influence anterior segment maturation. PubMed

20. Clinical spectrum linkage: PITX2 variants are a leading cause of ARS; iridogoniodysgenesis is one recognizable phenotype within that spectrum. NCBI+1

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Symptoms / signs

1. Iris hypoplasia (thin, under-developed iris; light can trans-illuminate). Arizona Genetic Eye Diseases Database

2. Corectopia (off-center pupil). North Bristol NHS Trust

3. Polycoria (multiple iris openings or pseudo-openings). North Bristol NHS Trust

4. Posterior embryotoxon (prominent Schwalbe’s line at the corneal edge). NCBI

5. Iris strands bridging to the angle (anterior synechiae/angle anomalies). NCBI

6. Goniodysgenesis (malformed drainage angle on gonioscopy). PMC

7. Juvenile or early-onset glaucoma (often in childhood/early adult life). PMC

8. Blurred vision or visual field loss from glaucoma if untreated. NCBI

9. Photophobia (light sensitivity) due to iris defects. NCBI

10. Corneal changes (endothelial/stromal abnormalities may occur in ASD). NCBI

11. Dental anomalies (small teeth, missing teeth) in syndromic PITX2 disease. NCBI+1

12. Facial features (maxillary hypoplasia, telecanthus/hypertelorism) in some. North Bristol NHS Trust

13. Umbilical anomalies (redundant periumbilical skin/hernia) in some families. NCBI+1

14. Hearing or cardiac anomalies (less common but reported). North Bristol NHS Trust

15. Family history with autosomal dominant pattern (parent and child affected). NCBI

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Diagnostic tests

A) Physical examination (at the slit-lamp or chairside)

1. Visual acuity testing: Baseline vision and monitoring for change from glaucoma or corneal/iris anomalies. NCBI

2. External inspection and pupillary exam: Detect corectopia, polycoria, iris transillumination; check light reactions. North Bristol NHS Trust

3. Intraocular pressure (IOP) assessment (screen): Palpation is crude; formal tonometry follows—high IOP suggests glaucoma. NCBI

4. Family examination: Look for similar iris/angle features or dental/umbilical signs in relatives (helps pattern recognition). NCBI

B) Manual / clinical instrument tests

5. Applanation tonometry: Accurate IOP measurement; repeated over time to detect glaucoma. NCBI

6. Slit-lamp biomicroscopy: Confirms iris hypoplasia, posterior embryotoxon, and abnormal iris strands. NCBI

7. Gonioscopy: Direct view of the drainage angle; reveals goniodysgenesis, broad synechiae, and high-risk angles. PMC

8. Pachymetry: Corneal thickness can influence IOP interpretation and may vary in ASD. NCBI

9. Visual field testing (perimetry): Detects glaucoma-related field loss. NCBI

C) Laboratory / pathological & genetic tests

10. Targeted PITX2 sequencing (Sanger/NGS panel): Looks for point mutations and small indels. IOVS

11. Copy-number analysis (MLPA/qPCR): Detects small deletions/duplications in PITX2. IOVS

12. Chromosomal microarray (array-CGH/SNP array): Finds larger 4q25 deletions covering PITX2. IOVS

13. Expanded ASD/ARS gene panel (includes FOXC1): Useful because PITX2 and FOXC1 pathways interact and phenotypes overlap. PubMed+1

14. Family (segregation) testing and genetic counseling: Clarifies inheritance and recurrence risk. NCBI

D) Electrodiagnostic tests

15. Optic nerve–related visual evoked potentials (VEP): Assesses pathway function when glaucoma damage is suspected but fields are unreliable (e.g., children). NCBI

16. Electroretinography (ERG): Generally normal in angle-based disease but helps rule out retinal causes of visual loss. NCBI

E) Imaging tests

17. Anterior segment OCT (AS-OCT): Cross-sectional images of the angle/iris to map goniodysgenesis non-invasively. NCBI

18. Ultrasound biomicroscopy (UBM): High-frequency ultrasound that shows angle membranes, iris processes, and ciliary body anomalies. NCBI

19. Optic nerve OCT (RNFL/GCC): Quantifies glaucoma damage to nerve fiber layers over time. NCBI

20. Fundus photography and optic nerve stereophotography: Visual record of the optic disc for longitudinal comparison. NCBI

Non-pharmacological treatments (therapies & others)

These are supportive, behavioral, optical, and care-coordination steps that improve life quality and protect vision. They work with medical/surgical glaucoma care, not instead of it.

1. Lifelong pediatric–ophthalmology follow-up. Early and regular visits help catch pressure spikes, optic-nerve change, and amblyopia. Coordinated care improves outcomes in anterior segment dysgenesis. Taylor & Francis Online+1

2. Family education & counseling. Clear teaching on glaucoma risk, eye-drop technique, signs of pressure rise (tearing, light sensitivity, big cornea), and adherence improves safety and surgery timing. PMC

3. Amblyopia (lazy eye) therapy. Patching or atropine penalization as indicated to strengthen the weaker eye once optical clarity/pressure are addressed. Glaucoma Today

4. Refractive correction (glasses/contacts). Corrects astigmatism, myopia, or hyperopia common in anterior segment disorders, reducing amblyopia risk. Taylor & Francis Online

5. Photophobia management. Tinted lenses, hats, and environmental adjustments help when iris hypoplasia causes light sensitivity. PMC

6. Low-vision rehabilitation (when needed). Magnifiers, contrast tools, school accommodations, and orientation services support reading and mobility if glaucoma has reduced vision. Taylor & Francis Online

7. Suture management after pediatric surgery. Early suture removal and careful steroid tapering after corneal or glaucoma surgery can reduce scarring and amblyopia risk. Glaucoma Today

8. Contact-lens options after corneal procedures. Specialty lenses may improve clarity if corneal shape is irregular. Taylor & Francis Online

9. Protective eyewear. Polycarbonate glasses to prevent injury in eyes with fragile anterior structures. Taylor & Francis Online

10. Treating surface irritation. Lubricants and lid hygiene can ease discomfort if exposure or irregularities cause dryness. Taylor & Francis Online

11. School/IEP support. Preferential seating, large print, and lighting control help children function better visually. Taylor & Francis Online

12. Genetic counseling. PITX2-related conditions are usually autosomal dominant; counseling helps families understand inheritance and testing of relatives. PMC+1

13. Systemic screening (as advised). In PITX2 spectrum, dentists/pediatricians may check for tooth and umbilical findings; coordinated care anticipates needs. PMC

14. Retinoic-acid–related teratogen avoidance in pregnancy. Because periocular development is RA-sensitive in models, avoid non-prescribed retinoids and discuss medications with obstetricians. (Mechanism inference from developmental data.) IOVS

15. Home symptom diary. Tracking tearing, photophobia, eye rubbing, or apparent eye enlargement supports timely clinic contact. PMC

16. Digital reminders/adherence tools. Timers and charts help with complex drop schedules that are common pre- and post-surgery. EyeWiki

17. Sun/UV precautions. Hats and UV-blocking lenses reduce glare and protect sensitive tissues. Taylor & Francis Online

18. Safe play guidance. Avoid high-impact eye risks; supervise activities to protect surgical eyes. Taylor & Francis Online

19. Psychosocial support. Rare-disease stress is real; family groups and counseling help coping and adherence. Taylor & Francis Online

20. Transition planning to adult care. Structured handoff preserves follow-up and pressure control across life. Taylor & Francis Online

Drug treatments

Drug choice is individualized by a pediatric glaucoma specialist. Many children ultimately need surgery, and drops are often an adjunct, especially in Axenfeld–Rieger/IGDS. Avoid brimonidine in very young children. NCBI+1

1. Timolol (β-blocker). Class: beta-blocker. Purpose/Mechanism: lowers aqueous production by blocking β-receptors in ciliary body. Dosage/Timing: typically 0.25–0.5% once–twice daily (pediatric dosing individualized). Side effects: bradycardia, wheeze; punctal occlusion reduces systemic absorption. Role: common first-line adjunct in pediatric glaucomas. EyeWiki

2. Betaxolol (β1-selective). Slightly less bronchospasm risk than timolol; otherwise similar notes; may be used if airway issues exist. EyeWiki

3. Dorzolamide (topical CAI). Reduces aqueous production by inhibiting carbonic anhydrase in ciliary processes. Often twice–thrice daily; stinging possible. Helpful as add-on. EyeWiki

4. Brinzolamide (topical CAI). Similar to dorzolamide; suspension can be more comfortable. EyeWiki

5. Acetazolamide (oral CAI). Systemic reduction of aqueous production; short-term bridge to surgery. Side effects: paresthesias, appetite loss, metabolic acidosis; adjust for weight. NCBI

6. Latanoprost (prostaglandin analog). Increases uveoscleral outflow; once nightly. Pediatric response can be variable in developmental glaucomas. Side effects: redness, lash growth. NCBI

7. Travoprost/Bimatoprost (PG analogs). Alternatives when once-nightly dosing preferred; consider similar cautions. EyeWiki

8. Brimonidine (α2-agonist). Reduces production and increases uveoscleral outflow but avoid under age 2 (CNS depression/apnea risk); use cautiously in older children. NCBI

9. Apraclonidine (α2-agonist). Short-term IOP lowering (e.g., peri-procedural); tachyphylaxis and allergy limit long-term use. EyeWiki

10. Netarsudil (Rho-kinase inhibitor). Increases trabecular outflow and reduces episcleral venous pressure; pediatric experience evolving; consider in specialist care. Side effects: conjunctival hyperemia. Taylor & Francis Online

11. Fixed combo: Timolol–Dorzolamide. Simplifies regimens to boost adherence; watch for additive side effects. EyeWiki

12. Fixed combo: Timolol–Brimonidine. Consider age limits due to brimonidine; may reduce drop burden in older children. NCBI

13. Fixed combo: Brinzolamide–Brimonidine. Add-on when β-blockers unsuitable; observe age/CNS cautions. NCBI

14. Topical steroids (post-op). Control inflammation after pediatric surgeries; careful taper and pressure monitoring are essential. Glaucoma Today

15. Topical cycloplegics (post-op comfort). Atropine or cyclopentolate to stabilize the iris and reduce pain/photophobia after specific procedures—by prescription only. Glaucoma Today

16. Hypertonic saline (when corneal edema present). Temporarily reduces corneal swelling to improve vision while definitive pressure control proceeds. Taylor & Francis Online

17. Antibiotic prophylaxis (peri-op only as indicated). Short courses around surgeries to reduce infection risk per surgeon protocol. Glaucoma Today

18. Lubricating drops/ointments. Support surface health when exposure or irregularity causes dryness/irritation; improve comfort and adherence to other drops. Taylor & Francis Online

19. IOP-spiking meds avoidance. Avoid or carefully monitor steroids (outside post-op need) and other agents known to raise IOP; coordinate with pediatricians. Taylor & Francis Online

20. Analgesics (short-term, age-appropriate). For post-op comfort only; dosing per pediatric protocols; avoid masking serious symptoms. Glaucoma Today

Note: In ARS/IGDS, medical therapy alone is often insufficient, and most children with significant glaucoma eventually need surgery. NCBI

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Dietary molecular supplements (supportive only)

No supplement can correct a PITX2 mutation or replace glaucoma surgery/drops. These items are adjuncts for general eye surface comfort or whole-child wellness—discuss with clinicians.

1. Omega-3 fatty acids (fish/algals). May support tear film quality and surface comfort; dietary sources prioritized; supplements only if advised. Taylor & Francis Online

2. Vitamin D (if deficient). General pediatric health; test-guided replacement only. Taylor & Francis Online

3. Vitamin A (dietary). Essential for ocular surface; avoid high-dose supplements; get from food unless clinician prescribes. Taylor & Francis Online

4. Lutein/Zeaxanthin (dietary greens). Antioxidant carotenoids for retinal health; emphasize food sources. Taylor & Francis Online

5. Vitamin C (dietary fruit/veg). General antioxidant support; routine diet is enough in most children. Taylor & Francis Online

6. Zinc (dietary). Adequate intake supports growth; avoid excess. Taylor & Francis Online

7. Probiotics (diet-based). Gut health support for overall wellness; evidence for eye pressure is lacking. Taylor & Francis Online

8. Hydration (water). Regular, moderate intake supports comfort; avoid rapid over-hydration “water-loading,” which can transiently affect IOP testing. Taylor & Francis Online

9. Balanced protein & iron (dietary). For normal child development; indirectly supports healing after procedures. Taylor & Francis Online

10. Avoid megadoses and “IOP-cure” claims. There’s no proven supplement that cures developmental glaucoma. NCBI

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Immunity-booster / regenerative / stem-cell drugs

There are no approved immune or stem-cell drugs that correct PITX2-related anterior segment malformation or “regrow” the drainage angle in children. Research into ocular development, neural crest biology, and cell-based repair continues, but clinical use here is not established. Always discuss trials with a specialist center. Frontiers

1. Biologic “immune boosters.” Not indicated for IGDS; no evidence they improve angle development. Avoid off-label use. Taylor & Francis Online

2. Hematopoietic stem-cell drugs. These treat blood disorders, not anterior segment formation; no role in IGDS. Taylor & Francis Online

3. Topical growth-factor drops (investigational). Limited contexts (e.g., epithelial healing) only; not angle regeneration. Taylor & Francis Online

4. Cell therapy for cornea (future). Research lines exist (e.g., endothelial cell therapy) but not specific to PITX2 drainage angle defects in children. Taylor & Francis Online

5. Gene therapy (concept). PITX2 is a transcription factor with complex timing and tissue targeting; no clinical gene therapy for IGDS currently. PubMed

6. Rho-kinase pathway targeting (approved as drops). Pharmacologic ROCK inhibition (e.g., netarsudil) helps outflow but is not “regenerative therapy.” Taylor & Francis Online

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Surgeries

1. Goniotomy. A tiny blade or probe opens the abnormal trabecular meshwork from inside the eye to improve outflow—often a first-line procedure for developmental angle issues. PMC

2. Trabeculotomy (ab externo). The surgeon opens Schlemm’s canal from outside to bypass malformed tissue—useful when angle anatomy makes goniotomy difficult. PMC

3. Trabeculectomy (filtering surgery). Creates a new drainage pathway under the conjunctiva; anti-scarring medications and close postop care are crucial in children. PMC

4. Glaucoma drainage device (tube shunt). A small tube diverts fluid to a plate reservoir; chosen when prior surgeries fail or anatomy is complex. PMC

5. Corneal procedures (when indicated). If corneal clarity is severely reduced, corneal surgery and aggressive amblyopia therapy may be needed to allow visual development. Glaucoma Today

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Preventions

We cannot prevent the genetic cause, but we can reduce complications and vision loss:

1. Early diagnosis through newborn/infant eye checks if family history exists. PMC

2. Keep all follow-up visits and pressure checks. PMC

3. Learn correct drop technique (punctal occlusion) to reduce systemic effects. EyeWiki

4. Protect eyes from injury (polycarbonate eyewear). Taylor & Francis Online

5. Control sun/glare exposure to reduce photophobia-related eye rubbing. PMC

6. Treat amblyopia promptly as directed. Glaucoma Today

7. Avoid contraindicated medications in toddlers (e.g., brimonidine under age 2). NCBI

8. Seek care rapidly for redness, pain, light sensitivity, or visible eye enlargement. PMC

9. Coordinate systemic and dental care in PITX2 spectrum. PMC

10. Plan transition to adult glaucoma care early. Taylor & Francis Online

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When to see a doctor (red flags)

See a pediatric ophthalmologist urgently for any of the following: new or worsening light sensitivity, tearing, eye rubbing, eye pain, redness, cloudy/large cornea, frequent headaches with nausea, or a sudden drop in vision or school performance. Children after glaucoma surgery need prompt review for discharge, pain, fever, or decreased vision. Families with known PITX2 variants should arrange early infant screening for siblings. PMC

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What to eat and what to avoid

Eat more:

1. Water throughout the day (steady intake).
2. Leafy greens and colorful vegetables (lutein/zeaxanthin, vitamin C).
3. Fish/plant omega-3s.
4. Whole grains, beans, lean proteins (healing, growth).
5. Fruits rich in vitamin C. Taylor & Francis Online

Avoid/limit:

1. Megadose supplements without prescription.
2. Energy drinks and rapid large fluid boluses just before clinic IOP checks.
3. Smoking exposure (household).
4. Rubbing the eyes (teach gentle dabbing).
5. Unverified “miracle cures” online. NCBI

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FAQs

1. Is iridogoniodysgenesis the same as Axenfeld–Rieger syndrome? They overlap. IGDS, iris hypoplasia, and ARS all sit on a spectrum; PITX2 mutations can cause any of them. PMC

2. What does PITX2 do? It “conducts” other genes so the front of the eye forms correctly. MedlinePlus

3. Is it inherited? Often autosomal dominant—each child has a 50% chance if a parent carries the variant—but expressivity varies. Genetic counseling helps. PMC

4. Will eye drops cure it? No. Drops lower pressure, but many children still need surgery. NCBI

5. Which drop is safest? Choice depends on age and health. Beta-blockers and topical CAIs are commonly used; avoid brimonidine under 2 years. Your specialist will tailor therapy. NCBI+1

6. Are prostaglandin drops helpful in kids? Sometimes, but response in developmental glaucomas can be limited. NCBI

7. What surgery is first? Goniotomy or trabeculotomy are common first steps for developmental angles; your surgeon decides based on anatomy. PMC

8. Will my child go blind? Many children maintain useful vision with timely surgery, drop use, and amblyopia care. Close follow-up is key. PMC

9. Are there body symptoms outside the eye? In the PITX2 spectrum, dental and umbilical findings can occur; your pediatrician/dentist may screen. PMC

10. Is gene therapy available? Not yet for PITX2/IGDS. Research is ongoing. PubMed

11. Can special diets fix eye pressure? No diet cures developmental glaucoma; a balanced diet supports recovery and overall health. NCBI

12. Will my other children need testing? Genetic counseling can discuss testing and early infant eye checks. PMC

13. Why do we need patching? To treat amblyopia so the brain learns to use the weaker eye. Glaucoma Today

14. Do kids outgrow this? The malformation is permanent; pressure control and visual development remain the goals. PMC

15. Are there support groups? Rare-disease and low-vision organizations can help with emotional support and school resources. Taylor & Francis Online

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: September 19, 2025.

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