Background: IRF6-related disorders span a spectrum from isolated cleft lip and palate and Van der Woude syndrome (VWS) at the mild end to popliteal pterygium syndrome (PPS) at the more severe end. Popliteal pterygia are found in popliteal pterygium syndrome, multiple pterygium syndrome and Arthrogryposis. The popliteal pterygium syndrome is a rare congenital condition, in which the patient has facial, genitourinary and skeletal anomalies along with popliteal pterygium. Autosomal dominant popliteal pterygium syndrome (AD-PPS) is a rare genetic malformation disorder characterized by cleft lip, with or without cleft palate, contractures of the lower extremities, abnormal external genitalia, syndactyly of fingers and/or toes, and a pyramidal skin fold over the hallux nail. AD-PPS is associated with mutations in the IRF6 gene (1q32.2-q32.3), involved in the formation of connective and epithelial tissues. Almost all affected patients harbor mutations in this gene. The word ‘pterygium’ is derived from the Greek word pterygion, which means wing. Pathologically it denotes a wing-like abnormal band of tissue. The most obvious characteristics of this syndrome are popliteal pterygium and a triangular crease of skin over the hallux. The orofacial findings include cleft lip, cleft palate, lower lip pits, a few missing teeth, and severely decayed teeth. The dental problems are overshadowed by the major syndromic manifestations. These patients have special dental needs and early preventive dental care and appropriate dental treatment at the optimal time is important. Diagnosis of pterygium syndrome is based on the clinical findings and confirmed by molecular genetic testing. AD-PPS is highly associated with missense mutations that alter residues that are predicted to interact directly with DNA in exons 3 and 4 of IRF6. Conclusion: An understanding of the molecular genetic basis of this syndrome is essential for prenatal diagnosis and also for genetic counseling of the parents. Keywords: Popliteal pterygium syndrome, Escobar syndrome, Magnetic resonance imaging, Congenital contractures, Genetic counseling.
Comparative analysis of IRF6 variants in families with Van der Woude syndrome and popliteal pterygium syndrome using public whole-exome databases
