IRF6 and the Van der Woude Popliteal Pterygium Syndromes and the Risk for Nonsyndromic Cleft Lip and Palate

Abstract

Abstract Van der Woude syndrome (VWS; OMIM 119300) is a highly penetrant, autosomal dominant orofacial clefting disorder. VWS is characterized by clefts of the lip and/or palate with accompanying paramedian lower lip pits. An allelic variant, the popliteal pterygium syndrome (PPS), includes additional features of lower extremity pterygia, genital anomalies, skin overlapping the great toe, and other occasional features. Mutations in the transcription factor interferon regulatory factor 6 (IRF6) account for most cases of VWS/PPS with limited evidence for locus heterogeneity. Although VWS and PPS are relatively rare disorders, common variants in IRF6 also contribute to isolated cleft lip and palate. Isolated cleft lip and palate is a common birth defect with a prevalence of approximately 1 per 1000 live births. Thus, IRF6 is a critical component of the molecular cascade driving development of the lip and palate. Gene expression studies and mouse models are now providing additional insights into the role of this gene and others in the IRF6 developmental pathway in both facial and epithelial development.