Multiple pterygium syndrome, Escobar variant (MPSEV) is a rare congenital condition, which is inherited with an autosomal recessive pattern. It has an unknown incidence but is more common among children from consanguineous relationships.
It is caused by a mutation in the CHRNG gene on chromosome 2q. This gene encodes the gamma subunit of the acetylcholine receptor (AChR), which is found in the foetus until around 33 weeks of gestation, when it is replaced by another subunit to form the adult AChR protein. The severity of the CHRNG gene mutation influences the severity of the condition and the complete absence of the gamma subunit will result in the lethal multiple pterygium syndrome. The clinical features of MPSEV are variable, but the condition is characterised by pterygia (excessive webbing) typically affecting the neck, axilla, digits (syndactyly), antecubital fossa, popliteal and intercrural areas. Akinesia, which may be identified before birth, also frequently results in arthrogryposis (congenital contractures), causing a crouched stance, and muscle weakness. Other typical findings include growth retardation, ankyloglossia (adhesions between the tongue and the palate), syngnathia (congenital bands of tissue between the maxilla and the mandible), cleft palate, lumbar lordosis and scoliosis. Typical facial features seen in patients with MPSEV are ptosis, down slanting palpebral fissures, epicanthal folds, micrognathia, long philtrum and low-set ears. Other orthopaedic manifestations or associations that have been reported include cervical spine fusion, rib fusion, hip dislocation, foot deformities, camptodactyly, absent patellae, and pectus excavatum. There are case reports describing abnormalities of the ear bones and conductive hearing loss, and two case reports describe patients with MPSEV who had cardiac defects (atrial septal defects). Males with this condition can have cryptorchidism and females can have missing or underdeveloped labia majora. People affected by MPSEV may also have respiratory distress at birth due to lung hypoplasia. Unlike other abnormalities of the AChR, MPSEV does not lead to myasthenic symptoms in later life as the gamma subunit is only expressed during foetal life. However, progressive webbing and scoliosis commonly cause significant reduction in lung capacity and an airway that is increasingly difficult to manage. Even though myasthenic features and abnormal muscle histopathology is not expected in CHRNG mutations, however, congenital diaphragmatic muscle weakness, diffuse myopathy, and myasthenic-like features have been frequently reported in CHRNG mutation patients which could be due to the role of γ-subunit AChR in muscle organogenesis.