Multiple Pterygium Syndrome

Disease Overview

Multiple pterygium syndrome (MPS) is a group of rare genetic disorders present at birth (congenital) characterized by numerous webbing (pterygia) of several parts of the body (neck, axilla, antecubital, elbow, interdigital and popliteal regions), multiple joint contractures (arthrogryposis) and skeletal abnormalities or deformities.¹

There are mainly two subtypes of multiple pterygium syndrome, lethal and nonlethal (Escobar). The lethal subtype is most severe and diagnosed prenatally with fetal ultrasound during the pregnancy because of multiple pterygia, hygroma colli and sometimes stillbirth. The nonlethal variant is Escobar syndrome, which includes numerous pterygia, joint contractures and distinctive facial features. Less common types of MPS include autosomal dominant MPS and X-linked MPS.¹

Multiple pterygium syndrome occurs due to disrupted communication between nerve and muscle cells during early fetal development. Most cases of MPS are caused by changes (variants) in the CHRNG gene, but some cases are caused by variants in other genes. Inheritance is typically autosomal recessive. Autosomal dominant, X-linked dominant, X-linked recessive, and sporadic cases have also been reported.¹

While there is no cure yet, early diagnosis and management are essential in improving outcomes for affected people.¹

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Subdivisions

• Escobar syndrome (autosomal recessive multiple pterygium syndrome, Escobar variant, multiple pterygium syndrome, autosomal recessive non-lethal multiple pterygium syndrome)
• lethal multiple pterygium syndrome (autosomal recessive lethal multiple pterygium syndrome, LMPS)
• autosomal dominant multiple pterygium syndrome (distal arthrogryposis type 8, contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A, contractures, pterygia, and variable skeletal fusions syndrome 1A; CPSKF1A)
• X-linked lethal multiple pterygium syndrome

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Signs & Symptoms

Multiple pterygium syndrome (MPS) is a rare genetic condition that affects movement before birth, leading to joint contractures (stiffness) and webbing of the skin across joints (pterygia). It results from reduced fetal movement (akinesia) during pregnancy which causes the muscles and joints to develop abnormally.¹

There are basically 2 different types of MPS, mild (Escobar syndrome) and severe and life-threatening (lethal multiple pterygium syndrome – LMPS).

Signs and symptoms vary according to the subtype and may include: ^1,2,4,5,6

Escobar syndrome (non-lethal MPS)

• Milder form of MPS, where individuals survive after birth
• Pterygia (webbing) mainly affects the neck, elbows, knees, fingers, and inner thighs
• Joint contractures (arthrogryposis multiplex congenita) may limit movement
• Facial features include:
  • Droopy eyelids (ptosis)
  • Downward-slanting eye openings (palpebral fissures)
  • Skin folds covering the inner corners of the eyes (epicanthal folds)
  • Small jaw (micrognathia)
  • High-arched palate
  • Low-set ears
• Other features may include:
  • Spine problems (scoliosis, vertebral fusions)
    • Scoliosis is seen in 32-93% of people with MPS
  • Limb abnormalities (missing kneecaps, clubfoot, joint dislocations)
  • Respiratory distress (due to underdeveloped lungs)
  • Genital abnormalities (undescended testes in males, abnormal female genitalia)
  • Short stature
  • Hearing loss

Escobar syndrome usually does not worsen after birth and some symptoms may improve with age and physical therapy. The outcome depends on the severity of the presenting symptoms and the promptness of intervention.

Lethal multiple pterygium syndrome (LMPS)

Lethal multiple pterygium syndrome (LMPS) is very severe and often fatal before birth or shortly after. LMPS has many of the same signs and symptoms as the Escobar type and, in addition, presents with:

• Problems presented before birth include:
  • Cystic hygroma (fluid-filled sac at the back of the neck, seen on ultrasound)
  • Fetal hydrops (severe fluid buildup in the body)
  • Severe joint contractures (leading to no movement)
• Organ and developmental abnormalities including:
  • Underdeveloped heart, lungs and brain
  • Intestinal malrotation (twisting of intestines)
  • Kidney defects
  • Cleft palate (an opening in the roof of the mouth)
  • Microcephaly (small head size)
  • Congenital diaphragmatic hernia (a hole in the muscle separating the chest and abdomen)

Most babies with LMPS do not survive past the second or third trimester of pregnancy.

Less common types of MPS include:

• Autosomal dominant MPS (formerly known as distal arthrogryposis type 8) or contractures, pterygia and spondylocarpostarsal fusion syndrome 1A. This is milder than LMPS but can cause:

• • Pterygia affecting the neck, underarms and behind the knees
  • Joint contractures in hands and feet
  • Severe scoliosis and short stature

• X-linked lethal MPS has the same life-threatening symptoms as LMPS including:

• • Severe joint contractures
  • Pterygia across multiple joints
  • Cystic hygroma and fetal hydrops
  • Cleft palate
  • Skeletal abnormalities
  • Fetal death in the second or third trimester

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Causes

Most cases of multiple pterygium syndrome are caused by changes (variants) in the  CHRNG gene, which plays a role in muscle development. This gene is responsible for making part of the acetylcholine receptor (AChR), a protein that helps nerve cells communicate with muscle cells. The variants in the CHRNG gene lead to problems with this receptor, disrupting nerve-muscle communication in a developing baby. As a result, muscle movement in the womb is reduced or absent, which contributes to the joint contractures and skin webs (pterygia) seen in MPS.^1,2

During early pregnancy, AChR contains a gamma (γ) subunit made by the CHRNG gene. Around week 33 of pregnancy, this γ subunit is replaced by an epsilon (ε) subunit, which is found in the adult form of the receptor.

Babies born with Escobar syndrome do not have ongoing muscle weakness after birth because, after birth, their acetylcholine receptors function normally with the adult ε subunit.² However, by this time, the effects of muscle weakness have already taken place, leading to permanent joint and muscle issues before birth.²

Non-lethal MPS or Escobar syndrome can be caused by variants in the CHRNG (commented above) MYH3 and TPM2 genes.²

• MYH3 gene, which is linked to distal arthrogryposis type 8 (DA8), an autosomal dominant form of MPS also known as contractures, pterygia, and spondylocarpotarsal fusion syndrome-1B and to other joint contracture disorders (Freeman-Sheldon syndrome, and Sheldon-Hall syndrome)²
• TPM2 gene, which plays a role in muscle development before birth but has less impact on muscles after birth²

In addition, variants in the CHRNA1, CHRNB1, CHRND,  RAPSN, DOK7, CNTN1 and SYNE1 genes have also been reported as causes of fetal akinesia deformation sequence, syndromes with myasthenia and with arthrogryposis and/or Escobar syndrome.

• CHRNA1, CHRNB1, CHRND, and RAPSN genes are involved in acetylcholine receptor function.
• CNTN1 and DOCK7 genes affect nerve development.

These genes are mostly active during fetal development, which explains why children with Escobar syndrome do not have muscle weakness after birth.²

Lethal multiple pterygium syndrome (LMPS) is caused by variants in the CHRNG gene. In addition, variants in the genes can cause LMPS and can also cause fast- or slow-channel congenital myasthenic syndromes.³

Studies trying to correlate the specific symptoms with the specific altered gene have found that the severity of symptoms may depend on which gene is affected and how much function is lost. It has been found that very severe scoliosis (a sideways curvature of the spine) is especially common in people who have MPS caused by CHRNG and MYH3 variants.²

X-linked lethal multiple pterygium syndrome is a rare form that affects male fetuses, and it is characterized by the typical lethal multiple pterygium syndrome presentation (multiple pterygia, severe contractures, cleft palate, fluid accumulation (hydrops) and skeletal problems), usually leading to fetal death in the second or third trimester. and with an X-linked pattern of inheritance.¹

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Affected populations

Multiple pterygium syndrome is very rare. While the exact prevalence is unknown, a 2022 study indicated that 75 patients with Escobar syndrome associated with variants in the CHRNG gene have been described in the literature. The prevalence of lethal multiple pterygium syndrome is unknown but is thought to be <1 in 100,000. There have been approximately 50 cases of lethal multiple pterygium syndrome (LMPS) reported in the medical literature.  It seems to be more common in males than in females.^4,5,7,8

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Disorders with Similar Symptoms

Symptoms of the following disorders may be like those of multiple pterygia syndrome. Comparisons may be useful for a differential diagnosis. Doctors consider the following conditions when diagnosing MPS to ensure the correct diagnosis:¹

Turner syndrome: Caused by a missing or incomplete X chromosome in females. Similar symptoms with MPS include webbed neck and extra skin folds on the neck, short stature and musculoskeletal problems (scoliosis, hip dislocation). However, Turner syndrome does not cause multiple body pterygia (skin webbing across joints) or joint contractures.

Noonan syndrome, a genetic condition affecting development. Similarities with MPS include some facial differences, including widely spaced eyes and a small jaw and heart problems. However, Noonan syndrome does not cause joint contractures or hearing loss.

Klippel-Feil syndrome, a syndrome with problems with the bones in the neck. The similarities with MPS include short neck with limited movement as well as scoliosis and back pain. However, Klippel-Feil syndrome does not cause skin webbing (pterygia). It mainly affects bones in the neck (cervical vertebrae fusion), leading to stiffness and chronic headaches.

Prune Belly syndrome (Eagle-Barrett syndrome) is a congenital condition affecting the abdomen and urinary system. Similarities with MPS include undescended testes (cryptorchidism) in males and clubfoot (foot deformity). However, it does not have pterygia as the MPS, it has severely weakened or absent abdominal muscles, causing the belly to appear soft and wrinkled (not found in MPS) and many other organ defects.

Van der Woude syndrome, a genetic condition affecting the mouth and face. Similarities with MPS include the cleft lip and cleft palate (opening on the roof of the mouth), but it does not have joint contractures or skin webbing (pterygia).

Arthrogryposis multiplex congenita (AMC), a general term for conditions that cause joint contractures before birth. Similarities with MPS include multiple stiff joints that limit movement. Genetic testing is needed to distinguish AMC from MPS.

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Diagnosis

Doctors use a combination of family history, physical examination, imaging and genetic testing to confirm the diagnosis of multiple pterygium syndrome.

Doctors will ask about family members with similar symptoms and whether the parents are related by blood (consanguinity), as this increases the risk of autosomal recessive MPS.

Ultrasound can detect signs of lethal multiple pterygium syndrome (LMPS) before birth such as:¹

1. • • Cystic hygroma (fluid-filled sac at the neck)
     • Joint contractures and skin webbing (pterygia)
     • Fluid buildup (fetal hydrops), which can be life-threatening

X-rays help identify skeletal abnormalities in suspected cases.

If MPS is suspected, doctors may recommend molecular genetic testing to confirm the diagnosis.^1,9

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Standard Therapies

Treatment

There is no cure for MPS, so treatment focuses on managing symptoms and improving the child’s quality of life.

Before birth (if LMPS is detected on ultrasound), if the pregnancy reaches full term, delivery should be considered high risk. Specialized care should be available at birth to manage breathing difficulties which can occur due to underdeveloped lungs (pulmonary hypoplasia) or a diaphragmatic hernia (a hole in the diaphragm).¹

After birth, babies with MPS should be evaluated by a genetic specialist. Care involves a team of doctors specializing in different areas. Parents should receive genetic counseling to understand the risk of having another child with MPS and available testing options for future pregnancies.¹

• Management is based on symptoms:^1,10
  • For joint contractures and pterygia:
  • Physical therapy to improve movement and prevent stiffness
  • Braces or orthopedic devices for support
  • Surgery can be done to correct severe contractures or joint deformities
• For breathing problems:
  • Newborns with lung underdevelopment may need oxygen or a ventilator
  • Pulmonologists (lung specialists) may help manage breathing difficulties
• For hearing loss:
  • Hearing aids or speech therapy for conductive hearing loss
  • ENT (ear, nose and throat) specialists can address frequent ear infections
• For feeding and nutrition:
  • Babies with a cleft palate may need special feeding techniques or surgical repair
  • Nutritionists may help prevent poor weight gain and malnutrition
• For spine and bone issues:
  • Scoliosis and kyphosis (spinal curvature) may require:
    • Bracing for mild cases
    • Surgery for mild and severe cases
      • Early surgery may help prevent severe spinal deformity
      • In severe cases, surgery can correct spinal alignment and reduce lung pressure, improving breathing and preventing further complications
    • For speech and developmental delays:
      • Speech therapy for speech delays or difficulty swallowing
      • Developmental pediatrics and occupational therapy to support learning and motor skills

Without proper care, MPS can lead to serious complications including:¹

• Breathing difficulties due to lung problems and rib abnormalities
• Severe joint stiffness causing mobility issues
• Speech and language delays
• Hearing loss which may impact communication
• Feeding difficulties leading to poor nutrition
• Heart problems which may contribute to heart failure
• Stillbirth or neonatal death in severe cases (LMPS)

Because MPS affects multiple body systems, children need a team of healthcare specialists, including genetic professionals (for diagnosis and genetic counseling), orthopedic surgeons (for joint contractures and scoliosis), neonatologists (for high-risk newborn care), anesthesiologists (for safe procedures and surgeries), developmental pediatricians (for growth and learning support), physical and occupational therapists (to improve movement and daily skills), pulmonologists (for breathing problems), cardiologists (for heart issues), audiologists (for hearing loss), otolaryngologists (for ear and airway concerns), radiologists (for imaging and diagnosis), endocrinologists (for hormonal concerns, if present) and urologists (for genital and urinary issues).^1,10

MPS is a lifelong condition that requires ongoing medical care. Early intervention with therapy and surgery can improve movement, breathing and overall health. Regular follow-ups with specialists are important to monitor complications. Genetic counseling can help families understand the condition and plan for future pregnancies.¹

The outlook for MPS depends on the severity of the symptoms. LMPS is often fatal before or shortly after birth. Escobar syndrome has a better prognosis, and many children can live independent lives with proper therapy and medical care. However, the outcome depends on the severity of the symptoms and the early interventions. Without treatment, scoliosis can worsen, making it harder to breathe and affecting overall health. ^1,10 

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]

Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/

For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/

For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

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References

1. Oboli VN, Carugno P. Pterygium Syndrome. [Updated 2023 May 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK592397/ Accessed Feb 4, 2025.
2. Manjunathan S, Singh K, Saini L. Multiple Pterygium Syndrome (Escobar Syndrome): A Rare Form of Prenatal Myasthenia Presenting With Arthrogryposis Multiplex Congenita. Neurology. 2024 Jul 23;103(2):e209602. doi: 10.1212/WNL.0000000000209602. Epub 2024 Jun 13. PMID: 38870465.
3. Zhuang J, Wang J, Luo Q, Zeng S, Chen Y, Jiang Y, Chen X, Wang Y, Xie Y, Wang G, Chen C. Case Report: Novel compound heterozygous variants in CHRNA1gene leading to lethal multiple pterygium syndrome: A case report. Front Genet. 2022 Aug 26;13:964098. doi: 10.3389/fgene.2022.964098. PMID: 36092864; PMCID: PMC9459375.
4. Lethal multiple pterygium syndrome. Orphanet. October 2019. https://www.orpha.net/en/disease/detail/33108 Accessed Feb 4, 2025.
5. Autosomal dominant multiple pterygium syndrome. Orphanet. https://www.orpha.net/en/disease/detail/65743 Accessed Feb 4, 2025.
6. X-linked lethal multiple pterygium syndrome. Orphanet. https://www.orpha.net/en/disease/detail/79447 Accessed Feb 4, 2025.
7. Najjar D, Chikhaoui A, Zarrouk S, Azouz S, Kamoun W, Nassib N, Bouchoucha S, Yacoub-Youssef H. Combining Gene Mutation with Expression of Candidate Genes to Improve Diagnosis of Escobar Syndrome. Genes. 2022; 13(10):1748. https://doi.org/10.3390/genes13101748
8. Mohtisham FS, Sallam A, Shawli A. Lethal multiple pterygium syndrome. BMJ Case Rep. 2019 May 8;12(5):e229045. doi: 10.1136/bcr-2018-229045. PMID: 31068350; PMCID: PMC6506140.
9. Manjunathan S, Singh K, Saini L. Multiple Pterygium Syndrome (Escobar Syndrome): A Rare Form of Prenatal Myasthenia Presenting With Arthrogryposis Multiplex Congenita. Neurology. 2024 Jul 23;103(2):e209602. doi: 10.1212/WNL.0000000000209602. Epub 2024 Jun 13. PMID: 38870465.
10. Dodson CC, Boachie-Adjei O. Escobar syndrome (multiple pterygium syndrome) associated with thoracic kyphoscoliosis, lordoscoliosis, and severe restrictive lung disease: a case report. HSS J. 2005 Sep;1(1):35-9. doi: 10.1007/s11420-005-0103-5. PMID: 18751807; PMCID: PMC2504136.

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Programs & Resources

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Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/

Rare Disease Educational Support Program

Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.

Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/

Rare Caregiver Respite Program

This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.

Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/

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More Information

The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.

GARD Disease Summary

The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).

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Orphanet

Orphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.

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