EC Clinical and Medical Case Reports

Escobar syndrome, the nonlethal variant of multiple pterygium syndrome, is a rare autosomal recessive disorder characterized by multiple joint pterygia, congenital contractures, and craniofacial anomalies. It results from impaired fetal movement during embryogenesis due to defective neuromuscular transmission, most commonly caused by mutations in the CHRNG gene encoding the fetal gamma subunit of the acetylcholine receptor. We report a 14-year-old female patient born to first-degree consanguineous parents who presented at birth with low weight, generalized hypotonia, and transient cyanosis. Early development was marked by global psychomotor delay and growth retardation. At one year of age, cardiac evaluation revealed tetralogy of Fallot, which was surgically repaired at five years with favorable outcomes. During childhood, she developed progressive polyarthralgias affecting multiple joints, accompanied by progressive joint contractures involving the hands and feet with tightened skin texture. Physical examination demonstrated bilateral hand deformities with thickened skin, limited finger extension, multiple osteotendinous retractions, and mild craniofacial dysmorphism including ptosis and down-slanting palpebral fissures. Whole-exome sequencing performed at 14 years confirmed a homozygous pathogenic variant in CHRNG, establishing the diagnosis of Escobar syndrome. The patient received multidisciplinary care involving cardiology, rheumatology, orthopedics, and physiotherapy. This case highlights the phenotypic variability of Escobar syndrome, particularly the rare association with complex cardiac malformations, and emphasizes the importance of genetic testing and coordinated long-term management. Enhanced clinical awareness is crucial for early recognition, especially in consanguineous populations.

 Keywords: Escobar Syndrome; Multiple Pterygium Syndrome; CHRNG Mutation; Arthrogryposis; Contractures; Tetralogy of Fallot

1. Hoffmann K., et al. "Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal gamma subunit”. American Journal of Human Genetics2 (2006): 303-312.
2. Morgan NV., et al. "Mutations in the embryonal subunit of the acetylcholine receptor (CHRNG) cause lethal and Escobar variants of multiple pterygium syndrome”. American Journal of Human Genetics2 (2006): 390-395.
3. ALGhasab NS., et al. "Cardiac anomalies associated with Escobar syndrome: a case report and a review of the literature”. Medicine30 (2021): e26687.
4. Karad S., et al. "Escobar syndrome with monodactyly: a rare case report”. Journal of Indian Association of Pediatric Surgeons5 (2022): 641-643.
5. Zhuang J., et al. "Novel compound heterozygous variants in CHRNA1 gene leading to lethal multiple pterygium syndrome: a case report”. Frontiers in Genetics 13 (2022): 964098.
6. Manjunathan S., et al. "Multiple pterygium syndrome (Escobar syndrome): A rare form of prenatal myasthenia presenting with arthrogryposis multiplex congenita”. Neurology 2 (2024): e209602.
7. Zhu X and Q Yao. "Novel heterozygous mutation in MYH3 causes contractures, pterygia, and spondylocarpostarsal fusion syndrome 1”. Medicine32 (2025): e43884.
8. Bayram Y., et al. "Molecular etiology of arthrogryposis in multiple families of mostly Turkish origin”. Journal of Clinical Investigation2 (2016): 762-778.
9. Marques FBC., et al. "Escobar syndrome: a multidisciplinary approach for an excellent outcome with 3 years of follow-up”. Cleft Palate Craniofacial Journal7 (2019): 970-977.
10. Sözbilen MC., et al. "Escobar (Multiple pterygium) syndrome: multidisciplinary approach to a very rare syndrome”. Eklem Hastaliklari ve Cerrahisi3 (2016): 171-174.