Popliteal Web Syndrome

Popliteal web syndrome means a baby is born with a tight web of skin and soft tissue behind the knee. This web tethers the thigh to the calf and blocks knee straightening, often causing a fixed bend at the knee. The web can run high from the buttock bone (ischium) down the back of the thigh and sometimes all the way to the heel, and the nerves and blood vessels to the leg can lie inside the web—so surgery must be planned carefully. The condition usually comes as part of a wider genetic syndrome called popliteal pterygium syndrome (PPS), which can also involve the face (cleft lip/palate, lower-lip pits), hands/feet (webbed or missing digits), and genitals. Most PPS is autosomal dominant and caused by changes (variants) in the IRF6 gene; rarer, more severe “multiple-pterygium” forms (for example Bartsocas-Papas syndrome) are autosomal recessive and involve RIPK4 or CHUK (IKKA) genes. PMC+3PubMed+3MedlinePlus+3

Popliteal web (pterygium) syndrome is a rare birth condition where a tight band of skin and fibrous tissue forms behind the knee and holds the leg in a bent position. It often appears as part of IRF6-related disorders—a spectrum that includes Van der Woude syndrome and popliteal pterygium syndrome (PPS). The web can contain or sit next to important nerves and blood vessels, so children may need careful imaging and staged surgery to safely release the band and restore knee extension. NCBI+1

This condition is usually genetic (autosomal dominant) and most often involves changes in the IRF6 gene. Many children also have other features such as cleft lip/palate, small pits of the lower lip, toe or finger fusion, and genital differences. Because arteries and nerves can run right next to the web, MRI and surgical planning are very important before any operation. PMC+2Nature+2

---

Other names

People may use several labels for the same clinical picture:

• Popliteal pterygium syndrome (PPS) – the most common term in medical genetics. MedlinePlus

• Congenital popliteal webbing – orthopedic/pediatric surgery wording focused on the knee web. Orthobullets

• Van der Woude spectrum / IRF6-related disorder – because PPS and Van der Woude syndrome are allelic (caused by different changes in the same gene, IRF6). NCBI+1

• Bartsocas-Papas syndrome (lethal PPS / autosomal-recessive PPS) – a more severe, often lethal multiple-pterygium condition with popliteal webs. PMC+1

---

Types

1. Autosomal-dominant PPS (classic PPS) – IRF6 variants; features include popliteal web, cleft lip/palate, lower-lip pits, limb and genital findings; severity varies even in one family. MedlinePlus+1

2. Autosomal-recessive multiple-pterygium form (Bartsocas-Papas syndrome) – usually more severe; many pterygia, severe facial and limb anomalies; high prenatal/neonatal mortality; associated with RIPK4 variants. PMC+1

3. PPS with ectodermal features / Cocoon spectrum – rarer forms related to CHUK (IKKA); share pterygia with prominent skin/ectodermal anomalies. PMC

4. Isolated congenital popliteal web – very rare cases where the web is the main or only anomaly; important to image the neurovascular bundle before surgery. Orthobullets

---

Causes

In PPS, “cause” mainly means genetic and developmental pathway problems that shape skin fusion and tissue separation before birth. I list them as distinct but related contributors.

1. IRF6 pathogenic variants (autosomal dominant): the single most common cause; IRF6 is a transcription factor guiding face, skin, and genital development. PubMed+1

2. Dominant-negative IRF6 effects: certain variants in DNA-binding domains interfere with normal protein and lead to more severe PPS features. PubMed

3. IRF6 haploinsufficiency: having only one working IRF6 copy disrupts normal tissue fusion (e.g., palate), explaining overlapping PPS/Van der Woude traits. PubMed

4. RIPK4 pathogenic variants (autosomal recessive): cause the severe Bartsocas-Papas phenotype with multiple pterygia including popliteal webs. PMC

5. CHUK (IKKA) variants: another recessive pathway defect; severe pterygium spectrum with ectodermal anomalies. PMC

6. Periderm formation failure: periderm is a temporary embryonic skin layer that prevents tissues from sticking together; IRF6/RIPK4/CHUK disruption impairs periderm, predisposing to adhesions/webs. PMC

7. Abnormal epithelial differentiation/apoptosis: developmental “un-sticking” of tissues does not occur fully behind the knee, leaving a web. PMC

8. Allelic heterogeneity at IRF6: different IRF6 changes can produce PPS or Van der Woude—explains family variability. Nature+1

9. De novo mutations: a new change appears in the child with unaffected parents; recurrence risk is usually lower but not zero. MedlinePlus

10. Parental germline mosaicism (suspected): a parent can carry the change in some reproductive cells without showing signs, explaining recurrence in rare families. (Inference from IRF6-related disorder patterns.) NCBI

11. Modifier genes: other genes can make the phenotype milder or more severe, explaining why one sibling may have only lip pits and another has a large popliteal web. NCBI

12. Variable expressivity: the same IRF6 change can cause different features across individuals; the popliteal web is one “expression.” Lippincott Journals

13. Reduced penetrance of lip pits/clefts: some carriers lack obvious facial signs yet pass on the variant; popliteal web can be the presenting clue. PMC

14. Consanguinity (recessive forms): increases risk of the RIPK4/CHUK-related severe multiple-pterygium phenotypes. PMC

15. Embryonic neurovascular course persistence: arteries/nerves may run close to or within the web because normal tissue remodeling did not complete. PubMed

16. Syndromic spectrum with Van der Woude: the same gene (IRF6) explains overlap; popliteal web appears in the “PPS end” of the spectrum. PubMed+1

17. Ectodermal dysplasia overlap: in CHUK/RIPK4-related disease, hair, nails, and skin anomalies point to a shared pathway cause for webs. PMC

18. Prenatal development timing: early facial and limb patterning windows are when IRF6 is highly active; disruption during these windows yields webs and clefts together. PubMed

19. Tissue band/synechiae formation in the mouth or eyelids: the same “tissues stick when they shouldn’t” mechanism that makes syngnathia or ankyloblepharon can form the popliteal web. PMC

20. Not caused by parenting or pregnancy behavior: no proven environmental cause or maternal action has been shown to create PPS. (Consensus from genetic-basis sources.) MedlinePlus+1

---

Symptoms & signs

1. Popliteal web behind the knee: a visible, tight skin/fibrous band that blocks knee extension; sometimes very extensive. PubMed

2. Fixed knee flexion deformity (contracture): the knee cannot fully straighten; can seriously limit walking. Fetal Medicine Foundation

3. Cleft lip and/or cleft palate: common facial features in PPS families. MedlinePlus

4. Lower-lip pits: small moist depressions in the lower lip; classic IRF6-related sign. NCBI+1

5. Syngnathia: fibrous bands in the mouth restricting opening. PMC

6. Ankyloblepharon: partial fusion of eyelids at birth. PMC

7. Syndactyly: webbed fingers or toes; sometimes missing or shortened digits. Wikipedia

8. Toenail dysplasia / nail anomalies: abnormal nails, often on toes. ResearchGate

9. Talipes (clubfoot): inward-turned foot in some children. PMC

10. Genital anomalies: cryptorchidism (undescended testes), bifid or malformed scrotum, labial hypoplasia. PMC+1

11. Normal growth and intelligence in classic PPS: most children with dominant PPS grow and learn normally once surgical issues are managed. PMC

12. Feeding and speech difficulties: mostly from the cleft palate; improve after repair and therapy. Children’s Hospital of Philadelphia

13. Gait problems/limp: due to knee contracture; improves with stepwise surgery and rehab. Lippincott Journals

14. Dental anomalies / missing teeth: occur in the IRF6 spectrum. NCBI

15. Severe multi-system problems in recessive forms: multiple pterygia, ectodermal signs, and higher mortality risk. PMC

---

Diagnostic tests

A) Physical examination (bedside)

1. Full newborn and limb exam: confirms a posterior knee web from thigh to calf/heel and measures how much the knee can straighten. Check skin, nails, digits, genitals, and face for the PPS pattern. Orthobullets

2. Craniofacial exam: look for lower-lip pits, cleft lip/palate, mouth bands (syngnathia), and eyelid bands (ankyloblepharon). These clues point to IRF6-related disease. NCBI+1

3. Neurovascular exam of the leg: palpate pulses and map sensation/motor function (tibial/peroneal nerves) because vessels and nerves can lie in the web, which matters for surgery. PubMed

4. Musculoskeletal survey: inspect hands/feet for syndactyly or missing digits; check feet for clubfoot. Wikipedia

5. Genitourinary exam: check for undescended testes or labial hypoplasia; these help confirm the syndrome pattern. PMC

B) Manual/functional tests (in clinic)

6. Goniometric range-of-motion testing: measures exact knee extension deficit and tracks progress across casting, splinting, or surgeries. Fetal Medicine Foundation

7. Contracture palpation and band “tension line” mapping: clinical mapping of the tightest portions guides where surgeons will release the web in stages. Orthobullets

8. Functional gait assessment (age-appropriate): documents limp, stride, and compensations; guides timing of orthopedic correction. Lippincott Journals

9. Airway and feeding evaluation: for cleft palate/syngnathia, to plan safe feeding and anesthesia for later repairs. Children’s Hospital of Philadelphia

C) Laboratory / pathological & genetic tests

10. Targeted IRF6 sequencing (child ± parents): first-line genetic test for dominant PPS/Van der Woude spectrum. Finding a pathogenic variant confirms diagnosis and inheritance. MedlinePlus

11. RIPK4 and CHUK (IKKA) sequencing: indicated when the phenotype is unusually severe or recessive; identifies Bartsocas-Papas or related forms. PMC+1

12. Chromosomal microarray / exome sequencing: used if targeted tests are negative or findings are atypical; can detect rare/novel changes. NCBI

13. Genetic counseling session and pedigree analysis: clarifies autosomal dominant vs recessive inheritance and recurrence risks for the family. NCBI

14. Prenatal diagnostic genetics: chorionic villus sampling (10–13 weeks) or amniocentesis (15–20 weeks) with IRF6 (± RIPK4/CHUK) testing if a familial variant is known. NCBI

D) Electrodiagnostic tests

15. Nerve conduction studies (selected cases): if there are unusual weakness/sensory findings or before complex releases, to assess peroneal/tibial nerve function that may course within the web. (Used selectively; imaging is primary.) PubMed

16. EMG (electromyography): rarely needed; helps distinguish true neuropathy from mechanical tethering in complex deformities. (Adjunctive.) PubMed

E) Imaging tests

17. MRI of the knee and popliteal fossa: key study for surgical planning; shows the path of arteries, veins, and nerves inside the web and the depth/extent of fibrous tissue. AJR American Journal of Roentgenology+1

18. Doppler ultrasound: maps blood flow and helps avoid vessels during staged releases; useful in infants. ScienceDirect

19. Prenatal ultrasound: can show limb pterygia, clubfoot, and facial clefts; prompts genetic testing and delivery planning. Wikipedia

20. CT angiography (selected cases): 3-D view of vessels when MRI is limited; reserved for complex or redo cases. ScienceDirect

Non-pharmacological treatments (therapies & others)

1) Staged surgical release with Z-plasty: Surgeons cut and re-arrange small triangular skin flaps to lengthen the tight area while excising the fibrous band. This protects nerves and vessels and allows more knee straightening. Often done in stages as the child grows. Lippincott Journals+1

Purpose & mechanism: free the tether; lengthen skin; reduce mechanical block. Lippincott Journals

2) Nerve mobilization/lengthening (grafting or fascicular shift): If the sciatic/tibial/peroneal nerves are short or adherent, surgeons may mobilize them or add autografts/allografts to safely gain extension. MDPI+1

Purpose & mechanism: restore slack and protect sensation/motor function. MDPI

3) Vessel mobilization/possible grafting: When arteries/veins course beside the band, meticulous mobilization or grafting avoids ischemia while permitting release. MDPI

4) Capsular and tendon releases: Tight joint capsule and hamstrings/gastrocnemius may need selective release to gain full extension safely. Lippincott Journals

5) Post-operative serial splinting/casting: After release, gradual serial extension splints or casts maintain gains and remodel soft tissue. ResearchGate

6) External fixation (Ilizarov) in severe contracture: A circular frame can progressively stretch soft tissues and correct joint position over weeks. ScienceDirect

7) Physical therapy (ROM & strengthening): Early, gentle range-of-motion with progressive quadriceps/hamstring balance sustains extension and function. PMC

8) Gait training and orthoses: Ankle-foot orthoses or knee orthoses can stabilize joints and improve walking while tissues heal. MDPI

9) Scar management with silicone sheeting/gel: Silicone devices hydrate the scar to reduce hypertrophic/keloid thickening over incisions. (FDA-cleared devices; not drugs.) FDA Access Data+2FDA Access Data+2

10) Desensitization and nerve-glide therapy (specialist guided): Gentle graded desensitization and monitored neurodynamic work can help symptoms when safe relative to anatomy. PubMed

11) Pain neuroscience education and pacing: Teaching families how to protect healing tissues and pace activity reduces setbacks. Lippincott Journals

12) Skin care and pressure relief: Padding, moisturizers, and frequent checks prevent skin breakdown under braces/casts. ResearchGate

13) Multidisciplinary cleft team care (if cleft present): Coordinate plastic surgery, ENT, speech, and dental care alongside the limb plan. NCBI

14) Prenatal counseling when diagnosed in utero: Parents learn expected surgeries, rehab, and outcomes; helps delivery planning. PubMed

15) Nutritional optimization for wound healing: Emphasize adequate protein (≈1.2–1.5 g/kg/day) and micronutrients that support collagen. ANFP

16) Vitamin C adequacy: Vitamin C is needed to make collagen, which helps wounds heal; avoid megadoses beyond ULs without clinician advice. Office of Dietary Supplements+1

17) Zinc sufficiency (avoid deficiency): Zinc participates in tissue repair; evidence suggests possible benefit, though quality is mixed. PMC+1

18) Post-op swelling control (elevation/ice as advised): Simple measures reduce edema and pain to protect repairs. Lippincott Journals

19) Home program & caregiver training: Daily gentle stretches, brace schedules, and skin checks maintain results. ResearchGate

20) Long-term follow-up through growth: Growth can tighten tissues again; periodic reviews catch early recurrence. rbcp.org.br

---

Drug treatments

Safety note: Doses and timing must be individualized by the treating clinician, especially for children. The drugs below are for pain control, infection prevention/treatment, anesthesia, scar/pruritus care, or DVT prophylaxis around surgery—not for “treating popliteal pterygium.” FDA labeling is cited for transparency.

1) Acetaminophen (paracetamol): baseline analgesic for post-op pain; follow max daily dose on label. FDA Access Data
2) Ibuprofen (oral NSAID): anti-inflammatory/analgesic; avoid if contraindicated; peri-op timing per surgeon. FDA Access Data
3) Ketorolac (injectable NSAID): short-term moderate-to-severe pain; strict duration limits to reduce bleeding/renal risks. FDA Access Data
4) Oxycodone oral solution (C-II): for severe pain unrelieved by non-opioids; carries boxed warnings (addiction, respiratory depression). FDA Access Data+1
5) Tramadol (C-IV): for moderate pain; watch for seizures and serotonin syndrome; not first-line in many pediatric settings. FDA Access Data+1
6) Lidocaine injection (local anesthetic): for regional blocks/infiltration by trained clinicians. FDA Access Data
7) Bupivacaine liposomal (EXPAREL): extended local anesthesia at the surgical site or specific nerve blocks in adults (pediatric use varies). FDA Access Data
8) Cefazolin (peri-op antibiotic): common first-line surgical prophylaxis when indicated, per local protocols. FDA Access Data
9) Amoxicillin-clavulanate (oral): for selected skin/soft-tissue infections after surgery if prescribed; dosing per FDA label forms. FDA Access Data
10) Clindamycin (oral/IV): option when beta-lactams aren’t suitable; monitor for C. difficile risk. FDA Access Data
11) Mupirocin topical (BACTROBAN/CENTANY): short courses for localized wound/site bacterial risk, per label. FDA Access Data+1
12) Enoxaparin (LMWH): VTE prophylaxis in select higher-risk post-op situations per surgeon/hematology. FDA Access Data
13) Apixaban (adult label): some centers use DOACs for specific indications; decisions are specialist-guided. FDA Access Data
14) Betrixaban (adult label; boxed warning): example anticoagulant labeling; use is highly individualized. FDA Access Data
15) Triamcinolone acetonide (KENALOG-10 intralesional): sometimes used off-label for hypertrophic scar modulation; route/strength per label cautions. FDA Access Data
16) Triamcinolone (other preparations): dosing/route differ (e.g., KENALOG-40/80 IM/intra-articular)—not for intradermal use; scar therapy uses the intralesional prep. FDA Access Data+1
17) Lidocaine topical systems (e.g., ZTlido): adjunct for localized post-op pain per label. FDA Access Data
18) Oxycodone medication guide (safe-use education): reinforces risk counseling for families when opioids are prescribed. FDA Access Data
19) Amoxicillin-clavulanate pediatric forms (ES-600/XR): specific formulations and dosing for pediatrics/adults per label. FDA Access Data+1
20) Clindamycin capsule labeling (historical and current): clarifies microbiology and safety points that guide use. FDA Access Data+1

---

Dietary molecular supplements

Always discuss supplements with your clinician, especially around surgery.

1) Protein/arginine-rich medical nutrition: higher protein supports collagen and tissue repair; many protocols aim for ~1.2–1.5 g/kg/day during healing; arginine is often included in wound formulas. ANFP+1

2) Vitamin C (ascorbic acid): essential for collagen cross-linking and wound tensile strength; keep within NIH upper limits unless your clinician advises otherwise. Office of Dietary Supplements+1

3) Zinc: co-factor in DNA synthesis and epithelial repair; evidence suggests benefit but quality is mixed—avoid excess. PMC+1

4) Vitamin A & E (as part of formulas): included in some wound products; roles in epithelial growth and oxidative balance; evidence varies. PMC

5) Selenium & Copper: trace elements in some wound supplements for antioxidant enzymes and collagen crosslinking. PMC

6) Omega-3 fatty acids (EPA/DHA): may modulate inflammation; effects on wound healing are context-dependent and sometimes mixed—avoid high doses right before surgery without clinician input. PMC+2PMC+2

7) Multinutrient wound formulas: combination drinks/shakes used in trials showed improvements in pressure-ulcer healing alongside standard care. PMC

8) Adequate total calories: energy sufficiency prevents muscle loss and supports immune and fibroblast activity. PA Foundation

9) Hydration: fluids support perfusion and nutrient delivery to healing tissues. PA Foundation

10) Balanced diet pattern (whole foods): lean proteins, fruits/vegetables, whole grains support micronutrient needs (professional guidance recommended). ANFP

---

Immunity-booster/regenerative/stem-cell” drugs

There are no FDA-approved regenerative or stem-cell drugs for popliteal pterygium or for “boosting immunity” in this context. Approved cell therapies (e.g., hematopoietic progenitor cell products) have unrelated indications, and FDA warns against unapproved stem-cell uses. The most ethical, evidence-based approach is surgery + rehab + nutrition + complication prevention. I cannot invent drugs that don’t exist for this condition.

---

Surgeries

1) Multi-Z-plasty release + fibrous band excision: stepwise lengthening of skin with removal of the band; restores extension while protecting deep structures. Lippincott Journals+1

2) Nerve mobilization/lengthening (graft or fascicular shift): restores nerve slack if shortened or adherent; preserves motor/sensory function during extension gain. PubMed+1

3) Vessel mobilization/possible grafting: maintains blood flow when the artery/vein lies along the pterygium. MDPI

4) Capsular/hamstring/gastrocnemius release: treats the secondary soft-tissue contractures around the joint. Lippincott Journals

5) External fixation or staged approaches: Ilizarov or serial casting for very severe flexion contractures to gradually lengthen soft tissues. ScienceDirect

---

Preventions

Because this is genetic, we cannot prevent the syndrome itself, but we can prevent complications and recurrence:

1. Early referral to a team with PPS experience. Lippincott Journals

2. Pre-op MRI/vascular mapping to avoid nerve/artery injury. PubMed

3. Staged planning rather than single aggressive release in severe cases. Lippincott Journals

4. Post-op splinting protocol to maintain gains. ResearchGate

5. Regular PT follow-up during growth spurts. PMC

6. Scar care with silicone to reduce hypertrophic scarring. FDA Access Data

7. Nutrition optimization (adequate protein/micronutrients). ANFP

8. Skin checks under braces/casts to prevent pressure sores. ResearchGate

9. VTE risk assessment after big surgeries/immobilization. FDA Access Data

10. Genetic counseling for family planning. NCBI

---

When to see doctors

Seek care now if an infant/child has a fixed bent knee with a visible skin web, especially with cleft lip/palate or toe/hand webbing, because early imaging and planning improve outcomes. After surgery, seek urgent care for fever, wound redness, numbness, cold/pale foot, or sudden swelling/pain that could suggest infection or circulation problems. For long-term follow-up, review at set intervals—and sooner during growth spurts—so braces, therapy, or additional releases can be timed appropriately. PubMed+1

---

What to eat

Eat:

1. Protein-rich foods (eggs, dairy, fish, legumes, lean meats) to reach ~1.2–1.5 g/kg/day during wound healing. ANFP
2. Vitamin-C sources (citrus, berries, peppers) to support collagen; stay within safe upper limits unless directed. Office of Dietary Supplements
3. Zinc-containing foods (meat, beans, seeds) if your diet lacks them—avoid high-dose supplements without advice. PMC
4. Colorful fruits/veggies & whole grains for micronutrients and fiber to prevent constipation (common with opioids). PA Foundation
5. Adequate fluids for perfusion and bowel regularity. PA Foundation

Avoid/Limit:

1. Ultra-processed, high-sugar foods that displace protein/nutrients. ANFP
2. Very high-dose omega-3s right around surgery unless your surgeon agrees (mixed evidence; bleeding/inflammation nuances). PMC+1
3. Excess vitamin C or zinc above ULs without medical guidance. Office of Dietary Supplements
4. Alcohol and smoking exposure (impairs healing).
5. New supplements without checking for drug interactions.

---

FAQs

1) Is popliteal web syndrome curable?
Surgery can free the knee and improve walking, but children often need staged procedures, splints, and therapy as they grow. Lippincott Journals

2) Does any medicine dissolve the web?
No. Medicines help with pain, infection prevention, and anesthesia, but the web itself needs surgical release. Lippincott Journals

3) Is it genetic?
Yes, most cases are autosomal dominant and caused by IRF6 gene variants. NCBI

4) Can prenatal ultrasound find it?
Sometimes—especially when other PPS features are present; genetic testing can confirm. PubMed

5) Why do doctors order MRI?
To map the fibrous band and the exact position of arteries and nerves before surgery. PubMed

6) Will my child need nerve surgery?
If nerves are short or stuck to the band, surgeons may mobilize or graft them to allow straightening while protecting function. PubMed

7) What are the surgical risks?
Bleeding, infection, recurrence, and injury to nearby nerves/vessels—hence careful imaging and staged planning. Hong Kong Journal of Radiology

8) How soon does therapy start after surgery?
Usually early, with gentle motion and a brace/splint plan to maintain extension. ResearchGate

9) Do silicone sheets really help scars?
Yes, silicone sheeting/gel is FDA-cleared for hypertrophic/keloid scar management and is widely used. FDA Access Data

10) Are opioids always needed?
Not always. Teams aim for multimodal pain control (acetaminophen ± NSAIDs ± regional anesthesia), reserving opioids for breakthrough pain with careful counseling. FDA Access Data+1

11) Can nutrition speed healing?
Adequate protein and key micronutrients (vitamin C, zinc) support collagen and tissue repair. ANFP+1

12) Will my child walk normally?
Many do very well after staged releases, nerve/vessel protection, and consistent therapy, though individual outcomes vary. MDPI

13) What if the knee bends again?
Growth can tighten tissues; early follow-up allows timely bracing or additional release if needed. rbcp.org.br

14) Is this the same as multiple pterygium syndromes?
No—those involve multiple body webs and different genetics; popliteal pterygium in PPS is within the IRF6 spectrum. Radiopaedia

15) Should our family see genetics?
Yes—confirmation helps with counseling, recurrence risk, and planning for associated features. NCBI

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 04, 2025.

PDF Documents For This Disease Condition References