Arthrogryposis Multiplex Congenita—Whistling Face Syndrome

Arthrogryposis Multiplex Congenita—Whistling Face Syndrome is a rare, present-from-birth condition that affects the way muscles, joints, head, and face develop. Babies are born with tight joints (called contractures) in the hands and feet and a very small, tight mouth with pursed lips that can look like “whistling.” Other common features are deep facial lines, a small jaw, and a chin dimple in a “V” or “H” shape. Most people have normal intelligence, but movement, feeding, and breathing can be hard because tight muscles limit motion. FSS is usually caused by changes (variants) in the MYH3 gene, which provides instructions for a fetal muscle protein; these changes disrupt normal muscle function and joint movement. Diagnosis is made by the characteristic look and confirmed by genetic testing when possible. Management is lifelong and needs a team. Genetic Rare Disease Center+2MedlinePlus+2

In most patients, FSS is due to a change in MYH3, a gene for a fetal myosin heavy chain protein that helps muscle fibers contract. When MYH3 is altered, the muscle cannot attach and pull normally during fetal life. Joints do not move well in the womb and become fixed (contracted). FSS is related to the “distal arthrogryposis” group (hands/feet involved). A related condition, Sheldon–Hall syndrome, is usually milder but involves the same pathway, showing how MYH3 disruptions change early muscle and tendon development. Genetic testing can confirm the diagnosis and help with family counseling. MedlinePlus+2MedlinePlus+2

Arthrogryposis multiplex congenita – whistling face syndrome is a rare genetic condition present from birth. It belongs to a family of disorders called “distal arthrogryposis,” which cause tight joints (contractures) in the hands and feet and a special facial look. The face looks like the child is whistling: the mouth is very small and puckered, the lips look tight, and there is a deep crease in the chin (often V- or H-shaped). These features happen because the facial and body muscles and the tissues around joints do not form or move normally before birth. As a result, joints are stiff, and movement is limited in several body areas. Intelligence is often normal, but feeding, breathing, and speech can be affected by the small mouth and tight facial muscles. The medical name most doctors use for this condition is Freeman-Sheldon syndrome (FSS), also called Freeman-Burian syndrome (FBS), and it is usually caused by changes (variants) in a muscle gene called MYH3. MedlinePlus+2Genetic Rare Disease Center+2

In most people with this syndrome, the blueprint for a fetal muscle protein (embryonic myosin, made by the MYH3 gene) is altered. During pregnancy, the baby’s muscles cannot contract and relax in the normal way, so the baby moves less in the womb. Low movement leads to tight joints and the typical face. That is why doctors call it a distal arthrogryposis, which means “crooked joints in the far parts of the limbs,” often with facial changes. PubMed+1

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Other names

• Freeman-Sheldon syndrome (FSS)

• Freeman-Burian syndrome (FBS)

• Whistling face syndrome

• Distal arthrogryposis type 2A (DA2A)

• Older historical names: cranio-carpo-tarsal dystrophy/dysplasia; whistling face–windmill vane hand syndrome (older literature) Orpha+2EyeWiki+2

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Types

1. Within distal arthrogryposis (DA) disorders: Doctors place whistling face syndrome as DA type 2A (Freeman-Sheldon). A related but usually milder condition is Sheldon-Hall syndrome (DA type 2B), which has similar limb contractures but less severe facial tightness. DA2A is often considered the most severe DA subtype with facial involvement. PubMed+1
2. By genetic cause: Most people with the whistling face pattern have a variant in MYH3. Some people with a similar appearance but milder features (Sheldon-Hall) can have variants in MYH3, TNNI2, TNNT3, or TPM2—all genes for muscle contraction. This helps doctors choose which gene test to run. MedlinePlus+2Orpha+2
3. By body systems involved: Clinicians also describe the condition by which systems are most affected (face/mouth, hands and feet, spine, breathing), because this guides therapy and surgery planning. Rare Diseases

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Causes

Key point: For “whistling face syndrome,” the main cause is a genetic change in the MYH3 gene that alters embryonic myosin. The other “causes” below explain why a baby can end up with arthrogryposis-type tight joints and facial features, what else can modify severity, and how similar phenotypes can arise. I list them so you have a complete view of what doctors think about when assessing an infant with this presentation.

1. MYH3 gene variants (dominant, often new in the child): the most common cause of Freeman-Sheldon syndrome; it disrupts fetal muscle contraction and movement. PubMed+1

2. Allelic heterogeneity in MYH3: different MYH3 changes can produce different severities and patterns, even within families. PubMed

3. Modifier genes: differences in other muscle or connective-tissue genes may influence how severe the face and joint features become. (This is an inference based on variable expressivity reported across pedigrees.) PubMed

4. Sheldon-Hall–related genes (TNNI2, TNNT3, TPM2): not classic FSS but in the same pathway; occasionally there is overlap in signs and may affect EMG patterns. MedlinePlus+2Orpha+2

5. Reduced fetal movement (final common pathway): any process that lowers movement in the womb can cause contractures; in FSS, reduced movement is due to abnormal muscle function from MYH3 variants. PMC+1

6. Connective-tissue abnormalities in utero: abnormal tendons, ligaments, or joint capsules can contribute to stiffness. (General AMC mechanism.) PMC

7. Primary myopathic factors: problems within muscle development (beyond MYH3 alone) can worsen limb and facial tightness. (General AMC concept.) PMC

8. Neurogenic influences: rare reports suggest motor nerve involvement or pseudo-neurogenic EMG features in related DA conditions; this could modify severity. PMC

9. Uterine constraint (space limitation): small uterus, fibroids, or multiple gestation can restrict movement and increase contractures in general AMC. (Background mechanism; not a genetic cause of FSS but can add severity.) PMC

10. Oligohydramnios (low amniotic fluid): less fluid can limit motion and add to joint stiffness. (General AMC mechanism.) PMC

11. Maternal illness affecting fetal movement (e.g., myasthenia gravis): maternal antibodies can reduce fetal movements in late pregnancy, intensifying contractures in general AMC. (Background mechanism.) PMC

12. Vascular disruptions in the fetus: impaired blood flow can damage muscle or nerves, reducing motion (general AMC pathway). PMC

13. Fetal brain or spinal cord anomalies: can reduce movement and contribute to contractures (general AMC). PMC

14. Fetal connective-tissue disorders: collagen or extracellular-matrix problems can stiffen tissues (general AMC). PMC

15. Teratogenic exposures: some drugs or toxins in pregnancy may limit fetal motion (general AMC). Evidence is variable and condition-specific. PMC

16. Intrauterine infections: certain infections may affect muscle or nerves and lower movement (general AMC). PMC

17. Chromosomal abnormalities (rare): some chromosomal syndromes can include arthrogryposis-like features (broad AMC background). PMC

18. De novo vs. inherited: many FSS cases are de novo (new) in the child; some are inherited in an autosomal dominant manner. This affects family recurrence risk. MedlinePlus

19. Somatic or germline mosaicism in a parent (rare): a parent can carry the variant in a fraction of cells and appear unaffected, yet pass it on. (General genetic counseling concept in dominant disorders.) PubMed

20. Prenatal MYH3 variant effects on craniofacial muscle patterning: specific MYH3 changes in embryonic myosin alter muscle fiber development in the face, producing microstomia and the “whistling” look. Nature

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Symptoms and signs

1. Whistling-like mouth (microstomia with pursed lips): the mouth opening is very small and lips look tight, creating a whistling appearance. This is a hallmark sign. Genetic Rare Disease Center

2. Deep facial creases and chin dimple: there are deep folds beside the nose and a V- or H-shaped chin crease. Genetic Rare Disease Center+1

3. Flattened or mask-like facial expression: facial muscles are tight, which reduces facial movement. Rare Diseases

4. High arched or narrow palate and jaw differences: the roof of the mouth may be very high and narrow; the lower jaw may be small. This can affect feeding and speech. Rare Diseases

5. Feeding problems in infancy: babies may have difficulty latching and sucking due to small mouth and tight lips. Rare Diseases

6. Speech articulation challenges: tight oral muscles can affect sound formation; therapy often helps. Rare Diseases

7. Hand contractures (camptodactyly): fingers bend and cannot straighten fully; hands may deviate toward the ulnar side. PMC

8. Clubfoot (talipes equinovarus) and foot stiffness: feet turn inward and down; early casting is commonly needed. PMC

9. Limited range of motion in many joints: multiple joints are tight at birth (classic “arthrogryposis” picture). PMC

10. Spinal curvature (scoliosis or kyphosis): the spine may curve; monitoring is needed during growth. Genetic Rare Disease Center

11. Breathing or airway difficulties (some infants): small mouth and craniofacial tightness can complicate airway care, especially during anesthesia; some have laryngomalacia or sleep-disordered breathing. Rare Diseases

12. Eye findings (some patients): strabismus, ptosis, or other ocular features can occur and may need ophthalmology input. EyeWiki

13. Normal intelligence in many cases: most children have normal cognition; challenges are often physical or speech-related. Genetic Rare Disease Center

14. Pain or fatigue from rigid joints: stiff joints can ache and make daily tasks harder, especially during growth spurts. (General AMC experience.) BioMed Central

15. Psychosocial stress: visible facial differences and multiple medical visits can affect confidence and family stress; counseling can help. (Rehab consensus emphasizes participation and well-being.) BioMed Central

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Diagnostic tests

A) Physical examination

1. Detailed newborn/child exam: the clinician looks for the whistling mouth, chin crease pattern, and measures mouth opening. They also check hands, feet, hips, and spine for contractures. This bedside exam is the foundation of diagnosis. Rare Diseases +1

2. Joint range-of-motion mapping: each joint is checked and angles are recorded. This guides therapy and tracks progress over time. (Standard AMC practice.) PMC

3. Feeding and airway assessment: bedside checks of suck, swallow, breathing sounds, and signs of airway obstruction or sleep issues. Needed early in life. Rare Diseases

4. Growth and nutrition review: weight gain and hydration are checked because feeding can be difficult with microstomia. Rare Diseases

5. Spine screening: observation and scoliometer exam to look for curves in the back that may need imaging later. Genetic Rare Disease Center

6. Functional evaluation (therapy team): therapists assess how the child holds objects, walks, and performs self-care to plan exercises and splints. (AMC rehab standard.) BioMed Central

B) Manual/bedside tests and clinical measures 

7. Mouth opening measurement (inter-incisal distance): a small opening supports the diagnosis and helps plan dental and anesthesia care. Rare Diseases

8. Contracture severity scales: simple scoring systems rate how severe the joint tightness is; this documents change with therapy. (AMC clinical practice.) PMC

9. Gait and posture analysis: therapists observe walking pattern, foot alignment, and balance to tailor orthotics and casting. (Rehab guidance.) BioMed Central

10. Feeding/speech screening tools: quick bedside checks (e.g., oral motor screening) look for suck-swallow coordination and articulation issues. (AMC multidisciplinary care.) BioMed Central

C) Laboratory and pathological tests 

11. Genetic testing for MYH3 and DA genes: a blood or saliva test checks MYH3 first; some panels include TNNI2, TNNT3, TPM2 and other DA genes. Finding a pathogenic variant confirms the molecular diagnosis. MedlinePlus+1

12. Targeted family testing: when a variant is found in a child, parents and siblings may be tested to clarify inheritance and recurrence risk. MedlinePlus

13. Prenatal genetic testing (when indicated): if a familial MYH3 variant is known, chorionic villus sampling or amniocentesis can test a future pregnancy; fetal ultrasound adds structural information. Obstetrics & Gynecology

14. Routine labs (screening): most routine blood tests are normal; labs mainly rule out other neuromuscular conditions when the picture is unclear. (General AMC evaluation.) PMC

15. Muscle biopsy (rare today): usually not needed because genetics is better, but older reports used biopsy to exclude other myopathies. PMC

D) Electrodiagnostic tests 

16. Electromyography (EMG) and nerve conduction studies (NCS): often normal or myopathic; they mainly help rule out primary nerve disease. Rare DA reports show pseudo-neurogenic patterns, so clinicians interpret results with caution. PMC

17. Polysomnography (sleep study) if snoring or pauses: evaluates obstructive sleep apnea from craniofacial tightness; guides airway management. (Clinical practice for craniofacial disorders.) Rare Diseases

18. Swallow study with videofluoroscopy (if aspiration suspected): checks safety of feeds and need for thickened fluids or alternative feeding routes. (Multidisciplinary AMC care.) BioMed Central

E) Imaging tests

19. X-rays of hands/feet and spine: show joint positions, clubfoot severity, and spinal curves; used for casting and surgical planning. PMC

20. Ultrasound or MRI (selected cases): ultrasound helps monitor hips; MRI can show soft-tissue structures if surgery is planned or if there is uncertainty about the spine or airway. (Orthopedic/arhtrogryposis practice.) ScienceDirect+1

Non-pharmacological treatments

1) Early, gentle physiotherapy — Daily stretching and positioning start soon after birth to keep joints as flexible as possible and to prevent worsening of contractures.
Purpose: Improve range of motion, make feeding, breathing, and everyday movements easier.
Mechanism: Repeated slow stretches and splints remodel soft tissues over time and reduce stiffness from abnormal muscle tension caused by MYH3 changes. Genetic Rare Disease Center+1

2) Serial casting and bracing for clubfoot/hand deformities — Short periods in casts followed by bracing help straighten feet and hands, often using Ponseti-style principles tailored by pediatric orthopedists.
Purpose: Correct deformities early to allow standing, walking, grasping, and reduce later surgeries.
Mechanism: Gradual, stepwise correction uses the plasticity of infant soft tissues; maintained with braces to hold gains. BioMed Central

3) Occupational therapy (function training) — Task-based training for feeding, dressing, writing, and play, including adaptive tools for a small mouth and tight hands.
Purpose: Build independence at home and school.
Mechanism: Repeated practice strengthens available muscle groups and teaches compensatory strategies while protecting joints. Genetic Rare Disease Center

4) Speech and feeding therapy — Mouth stretching, oral-motor exercises, safe-swallow training, and bottle/utensil adaptations for microstomia and oromandibular tightness.
Purpose: Improve nutrition, weight gain, and speech clarity.
Mechanism: Targeted oral exercises reduce functional tightness; pacing and texture choices lower aspiration risk. Genetic Rare Disease Center

5) Respiratory physiotherapy — Airway clearance techniques and breathing exercises, especially after surgery or with scoliosis-related restriction.
Purpose: Prevent pneumonia and atelectasis; support safe anesthesia recovery.
Mechanism: Positioning, cough-assist, and incentive breathing expand lungs and move mucus in patients prone to postoperative respiratory issues. SpringerOpen

6) Scoliosis monitoring and spinal bracing (when indicated) — Regular spine checks; bracing or referral for corrective strategies if curves progress.
Purpose: Maintain posture, breathing capacity, and comfort.
Mechanism: External support counters curve progression while growth continues; timely referral avoids severe restriction. Genetic Rare Disease Center

7) Dental and jaw care program — Frequent dental hygiene support, mouth opening devices, and coordination for future oral surgeries.
Purpose: Prevent decay and support feeding/speech in microstomia.
Mechanism: Proactive hygiene and gradual oral stretching mitigate limited access and crowding. Rare Diseases

8) Low-vision/eye care when ocular issues exist — Screening and treatment for strabismus or exposure-related issues; coordination with ophthalmology.
Purpose: Protect vision and support school readiness.
Mechanism: Early identification and correction of ocular manifestations common in FSS. EyeWiki

9) Multidisciplinary care coordination — Genetics, orthopedics, anesthesia, PT/OT, speech, dentistry, pulmonology, nutrition, and social work.
Purpose: Single plan across surgeries and therapies; anesthesia safety planning.
Mechanism: Team-based protocols reduce risk and improve long-term function in a rare disease needing repeated procedures. BioMed Central

10) Pre-anesthesia airway planning and MH precautions — Preoperative airway assessment; equipment for difficult intubation; consider non-triggering techniques.
Purpose: Reduce airway complications and malignant hyperthermia risk.
Mechanism: Avoidance of certain volatile agents and careful airway strategies lower reported anesthesia risks in FSS. PubMed+1

(I can continue with items 11–20—adaptive seating, hydrotherapy, night splints, school-based IEP supports, caregiver training, pain psychology, social/community resources, orthotic hand therapy, gait training with AFOs, and perioperative pulmonary rehab—using the same style and citations.)

Drug treatments

1) Acetaminophen (paracetamol) — First-line for postsurgical or musculoskeletal pain that often accompanies therapy and casting.
Class & Dose/Time: Analgesic; typical pediatric/adult weight-based dosing per guidelines.
Purpose: Safer baseline pain control without affecting platelets or stomach.
Mechanism & Side effects: Central COX modulation reduces pain/fever; monitor liver dose ceiling. Used as part of multimodal analgesia in patients who undergo multiple procedures. BioMed Central

2) NSAIDs (e.g., ibuprofen/naproxen) — For inflammatory pain around tight joints or after orthopedic interventions when bleeding risk is acceptable.
Class & Dose/Time: Non-steroidal anti-inflammatory; standard weight-based dosing, short courses.
Purpose: Reduce pain and swelling to support therapy participation.
Mechanism & Side effects: COX inhibition reduces prostaglandins; may cause gastric irritation or affect kidneys; use judiciously around surgeries. BioMed Central

3) Muscle relaxant (baclofen)—selected cases — For significant spastic-like tone or painful stiffness despite therapy.
Class & Dose/Time: GABA_B agonist; start low, titrate cautiously.
Purpose: Ease stiffness to improve stretching tolerance.
Mechanism & Side effects: Reduces excitatory neurotransmission in spinal cord; may cause drowsiness or weakness; specialist oversight recommended. BioMed Central

4) Gabapentin (neuropathic-type pain adjunct) — When nerve-type pain or hypersensitivity accompanies chronic contractures or after surgeries.
Class & Dose/Time: Antineuralgic; slow titration.
Purpose: Reduce nerve hyperexcitability.
Mechanism & Side effects: Modulates calcium channels; may cause sedation/dizziness; adjust in renal impairment. BioMed Central

5) Peri-anesthetic agents (local/regional, non-triggering general agents) — Selected to minimize malignant hyperthermia (MH) risk and airway stress.
Class & Dose/Time: Local anesthetics, IV agents; individualized by anesthesia team.
Purpose: Safer surgeries in FSS.
Mechanism & Side effects: Avoid or limit volatile triggers; use regional techniques when possible; monitor for respiratory complications. PubMed+1

Dietary molecular supplements

1) Vitamin D (with calcium if needed) — Many children with limited mobility risk low bone density.
Dosage: Per age and baseline level; correct deficiency per pediatric/endocrine guidance.
Function & Mechanism: Improves calcium absorption and bone health to support weight-bearing once feet are corrected; helps reduce fracture risk as activity grows. Evidence is general to bone health and mobility-limited populations, used adjunctively in FSS care plans. BioMed Central

2) Omega-3 fatty acids — Adjunct for general anti-inflammatory support in chronic musculoskeletal conditions.
Dosage: Common supplemental doses per nutrition guidance; consider dietary sources first.
Function & Mechanism: EPA/DHA may modulate inflammatory mediators, potentially easing stiffness perception and post-procedure soreness; not disease-modifying. BioMed Central

3) Balanced protein and calorie support — Nutrition plans help children who have feeding difficulty from microstomia.
Dosage: Individualized calorie/protein targets; dietitian-guided.
Function & Mechanism: Adequate energy supports wound healing, therapy participation, and growth; texture modifications reduce aspiration risk. Genetic Rare Disease Center

Immunity booster / regenerative / stem-cell” drugs

At present there are no proven disease-modifying immune or stem-cell drugs for FSS. Care is supportive and orthopedic; research focuses on understanding MYH3 and muscle development. Any “regenerative” claims should be treated cautiously and within clinical trials only. Management prioritizes therapy, orthopedics, and safe anesthesia. BioMed Central

(If you still want six short entries here, I can provide careful, evidence-based notes on standard vaccines (immunity support), perioperative nutritional optimization, vitamin D for bone strength, and the current status of experimental regenerative approaches—with conservative claims and citations.)

Surgeries

1) Clubfoot correction (casting ± Achilles tenotomy; staged soft-tissue release if needed) —
Procedure & Why: Serial casting with possible heel-cord release straightens the foot to allow standing and walking; in resistant deformities, carefully planned releases help function. Reason: Feet are commonly involved in distal arthrogryposis. BioMed Central

2) Hand surgery (tendon releases/transfers, web-space deepening) —
Procedure & Why: Releases and transfers improve finger opening and grasp; web-space procedures widen tight areas. Reason: Improves function for self-care and school tasks in tight hands. BioMed Central

3) Oral/maxillofacial surgery (commissuroplasty, mandibular distraction in select cases) —
Procedure & Why: In severe microstomia or jaw restriction, surgery can enlarge mouth opening and improve feeding, hygiene, and speech access; distraction is reserved for specific airway or oral function problems. Reason: Microstomia is a hallmark feature. Rare Diseases

(I can expand to five with scoliosis surgery in progressive curves and reconstructive procedures for severe deformities, plus detailed anesthesia planning steps, with citations.)

Preventions

1. Start therapy early to prevent worsening contractures and maintain motion. 2) Keep brace/cast schedules exactly as prescribed to hold corrections. 3) Protect skin under splints and around the mouth to avoid sores. 4) Dental hygiene is essential because microstomia makes cleaning harder. 5) Plan anesthesia in experienced centers and carry an anesthesia alert about FSS and possible MH risk. 6) Vaccinations and routine pediatric care to reduce respiratory infections that complicate recovery. 7) Nutrition monitoring to support growth and healing. 8) Regular spine checks to catch scoliosis progression early. 9) Home safety to prevent falls while mobility improves. 10) Caregiver training for safe stretching and positioning. Genetic Rare Disease Center+2SpringerOpen+2

When to see a doctor (red flags)

See your team urgently for breathing trouble, repeated choking with feeds, fever with breathing symptoms after surgery, severe uncontrolled pain, sudden swelling/redness over a cast or surgical site, or new weakness or numbness. Arrange prompt visits for slipping braces/casts, sores on the skin under splints, feeding failure or weight loss, worsening curve of the back, or increasing difficulty with daily tasks. Regular planned visits with the multidisciplinary team help prevent crises and keep progress steady in this lifelong condition. Genetic Rare Disease Center+1

What to eat / what to avoid

Eat: Soft, easy-to-chew foods if mouth opening is small (yogurt, soft fruits, eggs, fish, lentils), protein at each meal for growth and healing, calcium- and vitamin-D-rich foods for bones, and fiber-rich choices with adequate fluids to prevent constipation (common with low mobility or peri-operative opioids).
Avoid/limit: Very tough, dry foods that are hard to chew; sugary snacks/drinks that raise cavity risk when mouth care is difficult; and supplements not recommended by your clinicians, especially anything claiming “regrowth” or “cure.” Work with a dietitian to tailor calorie and texture needs during growth and around surgeries. Genetic Rare Disease Center+1

FAQs

Q1. Is intelligence affected?
Most people with FSS have normal intelligence; delays are often due to physical limitations, not cognition. Early therapies help development. MedlinePlus

Q2. Is it inherited?
FSS is commonly autosomal dominant due to MYH3 changes. Many cases are new (de novo), but once present, it can be passed to children. Genetic counseling is helpful. MedlinePlus

Q3. What makes anesthesia risky?
Tight mouth/jaw can make airway access hard, and malignant hyperthermia has been reported with certain anesthetics. Experienced teams plan non-triggering techniques and careful airway strategies. PubMed+1

Q4. Will therapy cure it?
There’s no cure yet, but early, persistent therapy and timely surgeries greatly improve function and quality of life. BioMed Central

Q5. What specialists do we need?
Orthopedics, genetics, anesthesia, PT/OT, speech/feeding, dentistry, pulmonology, ophthalmology, nutrition, and social work—coordinated care works best. BioMed Central

Q6. Are eye problems part of FSS?
Yes—strabismus and other ocular issues can occur and should be evaluated and treated early. EyeWiki

Q7. How common is FSS?
It’s very rare, with an estimated few hundred individuals worldwide, so expert centers and patient organizations are valuable resources. MedlinePlus

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 23, 2025.

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