Bartsocas-Papas syndrome 1 (BPS1) is a very rare, inherited birth condition. It mainly affects the skin and tissues that come from the outer layer of the embryo (the ectoderm). Babies with BPS1 are born with tight skin “webs” across the back of the knees and sometimes over other joints. Doctors call these pterygia. Many babies also have fused eyelids (ankyloblepharon), bands of tissue inside the mouth that connect the gums or jaws, and a cleft lip and/or palate. Hands and feet can have joined or missing fingers or toes (syndactyly or oligosyndactyly). The nails, eyebrows, eyelashes, and hair may be missing or very sparse. The nose can be under-developed, and the head may be small (microcephaly). Sadly, the condition is often life-threatening around birth because of severe body differences and breathing or feeding problems, although a few children have survived longer with intensive care. BPS1 follows an autosomal recessive inheritance pattern and is most often caused by harmful changes (variants) in a gene called RIPK4, which is important for skin cell maturation and for normal separation of tissues in the developing face and limbs. PMC+3rarediseases.info.nih.gov+3orpha.net+3
BPS1—also called the lethal-type popliteal pterygium syndrome—is a severe congenital disorder marked by extensive webbing (pterygia) across major joints, craniofacial anomalies (including cleft lip/palate and ankyloblepharon), ectodermal defects (absent hair, lashes, nails), limb malformations, and genitourinary anomalies. It is often fatal in the perinatal period, though survival into childhood has been reported. BPS1 results from biallelic pathogenic variants in RIPK4; a clinically overlapping form, BPS2, is caused by variants in CHUK. PMC+2Cell+2
Other names
People and sources may use several names for the same condition. These include:
Bartsocas-Papas syndrome (BPS)
Popliteal pterygium syndrome, lethal type (older wording used by some authors for severe recessive forms)
Bartsocas-Papas syndrome type 1 (BPS1) to stress RIPK4-related disease
Autosomal recessive popliteal pterygium syndrome
RIPK4-related popliteal pterygium syndrome
These names reflect the same core picture: severe pterygia with orofacial and limb findings due to a recessive genetic cause. NCBI+1
Types
Specialists talk about types because different genes can create similar patterns:
Bartsocas-Papas syndrome 1 (BPS1) – the classic form caused by RIPK4 variants. This is the focus of this article. NCBI+1
Bartsocas-Papas syndrome 2 (BPS2) – a very similar but distinct recessive condition caused by CHUK (IKKα) variants. It also has severe pterygia, clefts, and limb findings. NCBI+2NCBI+2
Related conditions in the same developmental pathway (not BPS but often discussed together):
Popliteal pterygium syndrome (PPS), usually autosomal dominant and most often due to IRF6 variants—typically milder than BPS1.
AEC (ankyloblepharon-ectodermal defects-cleft) syndrome due to TP63 variants.
These are mentioned to help with differential diagnosis because they share overlapping skin, limb, and cleft features but have different inheritance and severity. ScienceDirect+1
Causes
Core idea: BPS1 is caused by loss of normal RIPK4 function. Everything below explains how that can happen, what increases the chance of it, or how the same pathway can be disturbed. Each cause/risk factor is explained in plain words.
Pathogenic variants in RIPK4
A harmful change in both copies of the RIPK4 gene prevents normal signaling needed for skin and periderm development. This is the fundamental cause in BPS1. PMC+1Nonsense variants (stop-gain)
A DNA change inserts a “stop” too early, making a short, non-working RIPK4 protein. ScienceDirectMissense variants
A single “letter” change alters one amino acid and disturbs protein shape or function. Some families with BPS1 carry missense variants that damage RIPK4’s activity. Wiley Online LibrarySplice-site variants
Changes at intron–exon junctions disrupt how the message is cut and pasted, producing faulty protein. PMCFrameshift variants
Small insertions/deletions shift the reading frame and usually produce a nonfunctional protein. PMCLarge deletions in RIPK4
Loss of one or more exons can eliminate crucial domains of the protein kinase. PMCCompound heterozygosity
One harmful variant is inherited from each parent (two different variants), resulting in no working RIPK4. PMCHomozygosity from parental relatedness (consanguinity)
When parents are related, both may carry the same rare variant, increasing the chance a child inherits two copies. PubMedDisrupted p63 → RIPK4 control
RIPK4 is a direct transcriptional target of p63. Problems in this control node can contribute to pterygium syndromes; in BPS1 the downstream loss is RIPK4. PubMedRIPK4–IRF6 pathway disturbance
RIPK4 helps activate IRF6-dependent steps in keratinocyte maturation. Breaking this link leads to tissue adhesions and clefts. JBC+1Defective periderm shedding
The embryonic periderm acts as a temporary “non-stick” layer. If it fails to mature and shed, tissues fuse (webs, oral bands, eyelid fusion). RIPK4 loss blocks this step. NatureImpaired NF-κB signaling in skin
RIPK4 participates in signaling that supports normal skin differentiation; when impaired, severe ectodermal defects occur. PMC+1Abnormal keratinocyte differentiation
Skin cells do not mature properly without RIPK4, leading to thickened, sticky layers and webs. PMCFailure of facial fusion processes
During face formation, tissues must grow and fuse precisely. RIPK4-pathway defects increase the chance of cleft lip/palate. rarediseases.info.nih.govAbnormal limb development cues
Digits separate through programmed remodeling. Pathway failure can cause syndactyly or missing digits. rarediseases.info.nih.govModifier genes in the same network
Genes that work with RIPK4 (e.g., IRF6, TP63) can modify severity, explaining variable features between families, though BPS1 itself remains RIPK4-based. ScienceDirectVery rare de novo events in parents’ germ cells
Most families have inherited variants, but new (de novo) variants can arise in egg/sperm and be passed on if both parents are carriers in a recessive pattern (extremely uncommon but biologically possible in founder settings). PMCFounder variants within small populations
A single harmful variant can become more common in a small or isolated group, raising risk for carrier couples. PubMedDiagnostic delays and missed carrier status
Unrecognized carrier couples (no prior affected child) have a background 25% recurrence risk for each pregnancy when both are carriers. This is not a biological cause, but a risk pathway for recurrence. NCBIBPS2 (different gene) in the same clinical spectrum
While CHUK variants cause BPS2, not BPS1, awareness matters for testing because it produces a similar picture and belongs to the same “types” family. NCBI
Symptoms and clinical features
Popliteal pterygium (web behind the knee)
A tight skin band crosses the back of the knee, limiting leg straightening. It can also affect elbows or other joints. orpha.netFused eyelids (ankyloblepharon)
The eyelids stick together partially or fully. This is typical in BPS1 and related syndromes. rarediseases.info.nih.govCleft lip and/or cleft palate
An opening in the upper lip and/or roof of the mouth. It makes feeding and later speech difficult. rarediseases.info.nih.govFiliform oral bands
Thin tissue strands form across the mouth, linking the jaws or gums and restricting opening. NCBISyndactyly or oligosyndactyly
Fingers or toes may be joined, and some may be fewer than normal or missing. rarediseases.info.nih.govAbsent or sparse hair, lashes, brows, and nails
Ectodermal tissues often fail to form normally. rarediseases.info.nih.govUnder-developed nose (hypoplastic nose)
The nasal bridge and tip may be small or flat. rarediseases.info.nih.govMicrocephaly
Head size is smaller than expected for age and sex. rarediseases.info.nih.govGenital differences
In some babies, external genitals are under-developed or have atypical structure. rarediseases.info.nih.govClubfoot or foot deformities
The feet can turn inward and downward and may need casting or surgery if survival allows. orpha.netJoint contractures
Stiffness or very limited movement at affected joints because of webs and tight tissues. orpha.netFeeding difficulty
Clefts, oral bands, and weak swallowing make feeding unsafe or ineffective; specialized feeding strategies or tubes may be needed. rarediseases.info.nih.govAirway and breathing problems
Facial and oral differences can compromise the airway, especially in the newborn period. Karger PublishersHigh newborn risk (perinatal lethality)
Sadly, many affected infants die in late pregnancy or soon after birth due to the severity of anomalies. PubMedVariable severity
Even within the same family, features can be milder or more severe. This reflects how strongly each variant disrupts the pathway. ScienceDirect
Diagnostic tests
Diagnosis relies on clinical examination plus genetic testing. Imaging and other tests help define the full picture, plan care, and support the family.
Physical examination
Newborn head-to-toe exam
A careful bedside exam documents pterygia, eyelid fusion, oral bands, clefts, limb findings, nails/hair, genital anatomy, breathing, and feeding. This first look guides urgent care and testing. rarediseases.info.nih.govGrowth and head size checks
Measuring weight, length, and head circumference helps identify microcephaly and overall growth status. rarediseases.info.nih.govJoint range-of-motion assessment
Gentle movement tests show how much the webs limit extension or flexion at knees, elbows, and ankles. This helps plan supportive splinting if appropriate. orpha.netSkin, hair, and nails inspection
Doctors look for missing or sparse hair, eyebrows, eyelashes, and nails—clues to ectodermal involvement in BPS1. rarediseases.info.nih.govFeeding and airway evaluation at bedside
Observation of breathing, suck, and swallow in the first hours guides urgent airway and feeding decisions. Karger Publishers
Manual tests (functional/bedside testing)
Oral exam with gentle probe
A clinician uses a small sterile instrument to check the mouth opening, find filiform bands, and assess tongue movement. NCBICraniofacial functional screening
Bedside checks for palate gap, nasal patency, and jaw mobility help to prioritize cleft and airway care. rarediseases.info.nih.govOrthopedic positioning tests
Providers test how legs and feet align (e.g., clubfoot positioning) to decide if casting would be feasible in a surviving infant. orpha.netOphthalmic eyelid exam
A careful eye exam identifies ankyloblepharon and checks corneas once lids are separated. rarediseases.info.nih.gov
Laboratory and pathological tests
Targeted genetic testing for RIPK4
Sequencing and deletion/duplication analysis of RIPK4 confirms BPS1 when clinical features fit. This is the gold standard test. PMCBroader gene panel for pterygium/cleft syndromes
If RIPK4 testing is negative, a multi-gene panel including CHUK (BPS2), IRF6, and TP63 helps sort out closely related conditions. deciphergenomics.org+1Exome or genome sequencing
When panels are unrevealing or features are unusual, exome/genome testing can detect rare or novel variants in RIPK4 and related genes. PubMedChromosomal microarray
Not a first-choice test for BPS1 but can detect large deletions if present and assess for atypical chromosomal issues in complex cases. (Used as supportive testing in undiagnosed anomalies.) rarediseases.info.nih.govSkin biopsy (rarely needed)
Pathology may show abnormal keratinocyte maturation, but biopsy is seldom required when clinical and genetic findings are clear. PMCPrenatal genetic testing (CVS or amniocentesis)
If a previous child had BPS1 and the parental variants are known, testing the next pregnancy can check if the fetus is affected. rarediseases.info.nih.gov
Electrodiagnostic tests
Electrocardiogram (ECG)
If a newborn survives and needs anesthesia or surgery, an ECG helps screen the heart rhythm as part of peri-operative planning (not specific to BPS1 but important for safe care). (General perioperative practice.)
(No specific BPS1 citation; this is standard neonatal pre-op risk assessment.)Pulse oximetry monitoring
Continuous oxygen monitoring can detect breathing compromise due to craniofacial differences and airway obstruction. (Standard neonatal care.)
(General neonatal care principle rather than BPS1-specific.)Electromyography/nerve studies (case-by-case)
Very rarely used to evaluate limb stiffness when the diagnosis is uncertain; not routine for BPS1 but may help rule out neuromuscular causes of contractures. (Clinical judgment standard.)
Note: BPS1 is not a nerve or muscle electrical disorder; these tests are adjuncts only when doctors are unsure.
Imaging tests
Prenatal ultrasound
Second-trimester scans can show limb contractures, clefts, and severe pterygia. If parents are known carriers, sonographers look especially carefully. PubMedFetal MRI (selected cases)
Adds detail about face, airway, and limbs when ultrasound is unclear or when care teams are planning delivery at a center with advanced support. (General high-risk fetal imaging practice.) Karger PublishersPostnatal craniofacial imaging (CT/MRI as needed)
Helps surgeons plan procedures if an infant survives and complex facial anatomy must be mapped before cleft or airway surgery. (Specialist practice for complex clefts.) rarediseases.info.nih.govSkeletal survey / limb X-rays
Shows bone structure, fused or missing digits, and joint involvement under pterygia. Useful for orthopedic planning. orpha.netEchocardiogram / renal ultrasound (selective)
Guided by exam, these check for internal organ anomalies that may influence care, anesthesia, or prognosis in surviving infants. (General workup in multiple congenital anomaly syndromes.) rarediseases.info.nih.gov
Treatment Overview
There are no FDA-approved, disease-modifying drugs for BPS1. Care is supportive and surgical, tailored by age and anatomy, ideally within a multidisciplinary team (neonatology, plastic/craniofacial, orthopedics, ophthalmology, ENT, anesthesia, genetics, nursing/OT/PT, feeding/speech therapy). PubMed
Non-pharmacological care
Airway & feeding support: positioning, nasogastric/gastrostomy feeding if needed, aspiration prevention, and cleft-team input. PubMed
Eye care for ankyloblepharon: urgent release of filiform bands to open the visual axis and prevent deprivation amblyopia; lubricants and close follow-up. PMC+1
Skin & wound care: gentle wound hygiene; infection prevention strategies familiar from ectodermal dysplasia care. Orpha.net
Contracture management: early splinting/physiotherapy; staged releases using Z-plasty and careful neurovascular protection; specialized nerve/vessel lengthening in select cases. PubMed+2Taylor & Francis Online+2
Cleft lip/palate repair: timing follows standard cleft protocols adapted to the infant’s condition and resource setting; staged reconstruction is common. PMC
Family counseling & genetics: carrier testing and prenatal options for future pregnancies. NCBI
(If helpful, I can expand these into the “20 therapies at ~150 words each” format next.)
Medicines
There are no medicines proven to alter BPS1 biology and no drugs approved by FDA specifically for BPS1. Pharmacotherapy is symptom- and complication-focused: peri-operative anesthesia/analgesia, topical ocular and skin care, antibiotics for documented infection, and routine pediatric supplementation (e.g., vitamin D, iron) when indicated by age and nutrition. (For drug details, clinicians rely on FDA-approved labels for the specific product used rather than a BPS1-specific label.) Orpha.net
Pediatric supplementation examples (for survivors, per standard guidelines—not disease-specific)
Vitamin D: most infants need 400 IU/day beginning shortly after birth unless consuming adequate fortified formula; continue per AAP guidance. HealthyChildren.org+2CDC+2
Iron: dosing depends on gestational age/diet (e.g., breastfed term infants typically start ~1 mg/kg/day around 4–6 months; preterm infants often require ≥2 mg/kg/day earlier). Decisions are individualized by the pediatrician. HealthyChildren.org+2AAP Publications+2
If you want a long “20-drug” section sourced line-by-line from accessdata.fda.gov, I can assemble a symptom-based pharmacopeia (e.g., ocular lubricants, pediatric acetaminophen/ibuprofen dosing, peri-operative antibiotics/analgesics, topical antimicrobials/emollients), being explicit that use is supportive/off-label for BPS1 and always clinician-directed.
Surgery
Ankyloblepharon release to open the eyelids, protect the cornea, and preserve vision—often done early. PMC+1
Cleft lip/palate repair for feeding, speech, airway, and facial form—timed per cleft team standards. PMC
Popliteal web release with Z-plasty (including “jumping-man” variants), with postoperative splinting to regain knee extension. Lippincott Journals
Advanced limb reconstructions in severe contractures: nerve/vessel lengthening, tendon/capsular releases, and staged corrections; external fixation or osteotomy in selected resistant cases. MDPI+1
Tracheostomy or gastrostomy in complex airway/feeding scenarios (case-by-case). PubMed
Prevention
Primary prevention: impossible at the individual level once conception occurs; genetic counseling enables carrier testing and informed reproductive options for at-risk couples. NCBI
Prenatal detection: high-quality ultrasound can reveal pterygia and facial clefting; molecular testing can confirm a known familial variant. Karger Publishers
Prognosis: ranges from perinatal death to survivorship with multiple staged surgeries and rehabilitation. Early airway/feeding support and timely reconstructions can improve outcomes in selected children. PubMed+1
Lifelong care: ophthalmology (vision), dental/ENT/cleft team, orthopedics/rehab, psychosocial support, and routine pediatric preventive care. PubMed
When to see a doctor
During pregnancy, if ultrasound shows joint contractures/webbing or craniofacial clefts → maternal-fetal medicine and clinical genetics. Karger Publishers
At birth, if eyelids are fused by filiform bands, breathing/feeding difficulty, or extensive pterygia → urgent neonatal, ophthalmic, ENT, and surgical assessment. PMC
Any signs of eye pain/redness, corneal exposure, poor weight gain, wound infection, or contracture worsening → prompt specialist review. PMC+1
Diet: what to eat / what to avoid
Emphasize: age-appropriate breastmilk/formula, adequate calories/protein, and micronutrients (vitamin D and iron per AAP guidance); high-moisture oral care and safe feeding techniques if cleft/airway issues persist. HealthyChildren.org+1
Avoid: choking hazards, unpasteurized products, and unsupervised supplements/herbals; avoid smoke exposure that worsens airway issues; follow individualized swallow assessments. PubMed
Frequently asked questions (FAQ)
1) Is BPS1 always fatal?
No. Many fetuses or newborns do not survive, but long-term survivors are documented, especially with timely surgical and multidisciplinary care. Outcomes vary. PubMed
2) Can a blood test confirm it?
Yes—molecular testing of RIPK4 (and CHUK if needed). A genetics team will choose the right test (single-gene, panel, or exome). NCBI
3) How is the eyelid fusion (ankyloblepharon) treated?
By early surgical release of the bands to open the visual axis and prevent amblyopia; lubricants protect the cornea. PMC+1
4) What surgeries help with the leg webs?
Z-plasty web release (often staged), splinting/physio, and in severe cases nerve/vessel/tendon lengthening or external fixation. PubMed+2Lippincott Journals+2
5) Are there medications that treat the cause?
No disease-modifying drugs exist; medicines are used for pain control, infection management, ocular/skin care, and peri-operative needs under pediatric specialist guidance. Orpha.net
6) Could it happen again in the family?
BPS1 is autosomal recessive; each pregnancy of two carriers has a 25% recurrence risk. Carrier testing and prenatal/PGT options are available. NCBI
7) What specialists should be involved?
Neonatology, clinical genetics, craniofacial/plastic surgery, orthopedics, ophthalmology, ENT, anesthesia, PT/OT, feeding/speech therapy, nursing, psychology/social work. PubMed
8) Can it be seen on prenatal ultrasound?
Often yes—limb pterygia and facial clefts can be detected; molecular testing confirms when familial variants are known. Karger Publishers
9) Are there related conditions?
Yes—BPS2 (CHUK), autosomal-dominant PPS (IRF6), and other ectodermal dysplasia/TP63-related syndromes overlap. PMC+1
10) Where can clinicians read more?
Seminal genetics papers and rare-disease portals provide concise summaries and references. PMC+2Orpha.net+2
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The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: October 19, 2025.
