Multiple pterygium syndrome

Overview

Multiple Pterygium Syndrome (MPS) is a rare congenital disorder characterized by web-like skin folds (pterygia) across joints, joint contractures (arthrogryposis), scoliosis, and a range of craniofacial, musculoskeletal, and genital abnormalities. The term "pterygium" refers to a wing-like web of skin, most commonly seen in the neck, elbows, knees, and fingers. These pterygia often restrict movement and contribute to significant joint stiffness from birth.

MPS exists in two main clinical forms:

• Lethal form: Severe presentation that often results in intrauterine death or death shortly after birth.

• Non-lethal (Escobar type): Milder form compatible with life, though affected individuals face physical limitations and require long-term medical care.

Due to its complexity and variability, Multiple Pterygium Syndrome requires multidisciplinary evaluation and management. While no cure exists, many individuals with the non-lethal form lead meaningful lives with supportive treatment.

Causes

Multiple Pterygium Syndrome is primarily caused by mutations in genes that regulate fetal development, muscle function, and neuromuscular junction signaling. The most commonly implicated gene is CHRNG, which encodes the gamma subunit of the acetylcholine receptor.

Genetic Features

• CHRNG mutations: Most frequently associated with the Escobar type of MPS. This gene plays a crucial role in the formation and function of neuromuscular junctions during fetal development.

• Other genes: Mutations in genes such as CHRND or CHRNA1 may also be involved in some cases.

• Inheritance patterns:

  • Autosomal recessive inheritance is most common, meaning both copies of the gene must be mutated for the condition to manifest.

  • Rare autosomal dominant and X-linked patterns have also been reported.

Consanguinity (parents being closely related) is often reported in families with affected children due to the autosomal recessive inheritance pattern.

Symptoms

The symptoms of Multiple Pterygium Syndrome vary depending on the severity of the condition. Individuals with the non-lethal (Escobar) type typically present at birth with characteristic features involving the skin, joints, spine, and facial structure.

Common Features

• Webbing (pterygia) of the neck, elbows, knees, fingers, and toes

• Joint contractures (arthrogryposis) leading to limited range of motion

• Scoliosis or kyphosis (spinal curvature)

• Short stature and growth delays

Craniofacial Abnormalities

• Low-set ears

• Micrognathia (small lower jaw)

• Ptosis (drooping eyelids)

• Cleft palate (occasionally)

Genital and Urogenital Anomalies

• Cryptorchidism (undescended testes) in males

• Hypoplastic or malformed genitalia

Other Possible Manifestations

• Congenital heart defects (rare)

• Hearing loss (conductive or sensorineural)

• Respiratory difficulties in severe forms

• Feeding difficulties in infancy

In the lethal form, features are more severe and may include hydrops fetalis, severe thoracic hypoplasia, and early neonatal death due to respiratory failure.

Diagnosis

Diagnosis of Multiple Pterygium Syndrome is based on clinical features observed at birth, family history, imaging studies, and genetic testing. Prenatal diagnosis may be possible in severe cases via ultrasound and molecular testing.

Postnatal Diagnostic Steps

• Physical examination: Identification of pterygia, contractures, facial features, and spine abnormalities

• X-rays: To assess skeletal anomalies, scoliosis, and joint contractures

• Echocardiogram: To detect any congenital heart defects

• Hearing tests: Audiologic evaluation to assess hearing loss

• Genetic testing: Confirmation of mutations in CHRNG or related genes

Prenatal Diagnosis

• Ultrasound may show joint contractures, fetal akinesia (reduced movement), or limb abnormalities

• Genetic testing via chorionic villus sampling (CVS) or amniocentesis if there is a known familial mutation

Treatment

There is no cure for Multiple Pterygium Syndrome, but supportive and symptomatic treatments can significantly improve quality of life and functional abilities. Management typically involves a multidisciplinary team including orthopedists, physiotherapists, geneticists, and speech or occupational therapists.

1. Orthopedic Management

• Physical therapy to improve joint mobility and prevent worsening contractures

• Surgical correction of contractures, scoliosis, or limb deformities

• Bracing or spinal fusion in cases of severe scoliosis

2. ENT and Speech Therapy

• Hearing aids or surgical correction for hearing loss

• Speech therapy for communication difficulties, especially if cleft palate is present

3. Respiratory and Feeding Support

• Management of airway difficulties in neonates with micrognathia

• Feeding therapy or gastrostomy tubes if oral intake is insufficient

4. Genetic Counseling

• Important for affected families to understand recurrence risks

• Carrier testing for siblings and prenatal testing for future pregnancies

Psychological and social support are also important to help families cope with the chronic nature of the condition and its physical limitations.

Prognosis

The prognosis for individuals with Multiple Pterygium Syndrome depends on the form and severity of the condition. The non-lethal Escobar type has a favorable outlook, with many individuals surviving into adulthood with varying degrees of physical disability. The lethal form has a very poor prognosis, with death occurring in utero or shortly after birth.

Favorable Factors

• Diagnosis of the non-lethal form with early physical therapy and supportive care

• Absence of severe respiratory or cardiac anomalies

• Normal intellectual development (common in the Escobar type)

Challenges

• Severe physical limitations due to contractures and scoliosis

• Multiple surgeries and long-term rehabilitation

• Psychosocial impact on patients and families

With early intervention and comprehensive care, individuals with Escobar-type Multiple Pterygium Syndrome can achieve improved mobility and participate in daily activities. Lifelong follow-up is usually necessary to monitor and manage complications as they arise.