IRF6 is a transcription factor with a highly conserved helix-turnhelix DNA binding domain and a less conserved SMIR/IAD protein-binding domain ( 14). Moreover, it has been shown that patients with VWS are more likely to have wound complications following cleft repair, including fistulae recurrence ( 13), and are more likely to require pharyngeal flap surgery ( 10– 12).

Other VWS features include greater prevalence of midfacial hypoplasia, and hypodontia ( 10– 12). Mixed clefting types is a common observation in different relatives with VWS within the same family ( 6– 9), further elucidating the variable phenotype observed even among cases carrying the same mutations. However, in approximately 25% of VWS cases, the causal mutation and gene remain unknown. Mutations in the gene IRF6 account for 70% of VWS cases, while mutations in the gene GRH元 account for another 5%. About 44% of the cases with VWS display lip pits as their sole phenotype ( 1, 4, 5), but cases with VWS can also show cleft lip (CL), cleft lip and cleft palate (CLP) or cleft palate (CP), all with or without lip pits demonstrating the marked variable expression. It is an autosomal dominant condition that accounts for 2% of all cases with orofacial clefts ( 2, 3). Van der Woude Syndrome (VWS) is among the common syndromic form of clefts, affecting 1/35,000 individuals ( 1). While most of the cases of cleft lip and palate are nonsyndromic (1 in 700–2,500 births), orofacial clefts have currently been associated with over 460 syndromes with known molecular basis.

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