Van der Woude syndrome is a developmental abnormality characterized by paramedian lower lip pits (fistula labii inferioris congenita) with or without cleft lip and/or cleft palate. Other less frequent features include cleft uvula and hypodontia, missing central and lateral incisors, canines, and/or bicuspids. Van der Woude syndrome is inherited as an autosomal dominant trait with high penetrance (96.7%) and variable expressivity ranging from a single barely evident depression to bilateral fistula of the lower lip and from a bifid uvula to a complete cleft palate and lip, determining various degrees of clinical relevance. It is the most common of the syndromic orofacial clefts, with prevalence in the general population estimated at 1 in 60,000. Treatment for the sequella of van der Woude syndrome includes cleft repair and ventilating tube insertion in patients with otitis media.
Linkage and cytogenetic analysis allowed mapping of the van der Woude locus to 1q32-q41.3. Recently, it has been shown that mutations in the gene encoding the transcription factor interferon regulatory factor 6 (IRF6) cause van der Woude syndrome, and that IRF6 is highly expressed in the medial edges of the paired palatal shelves around the time of fusion. Van der Woude syndrome can be caused by loss of function mutations that result in loss of both the DNA-binding and protein-binding functions, or by IRF6 gene deletions that result in haploinsufficiency.