Van der Woude Syndrome (VWS) is the most common form of syndromic cleft lip and palate and accounts for about 2% of all cleft lip and palate cases. Distinguishing characteristics include cleft lip with or with out cleft palate, isolated cleft palate, bilateral lip pits, hypodontia, normal intelligence, and an autosomal dominat mode of transmission with a high degree of penetrance.

The VWS locus has been mapped to a 1.6cM region of chromosome 1q32 by linkage analysis and the discovery of a microdeletion around D1S205. One YAC, yCEPH785B2, contains both flanking markers, D1S491 and D1S205, and encompasses the microdeletion. The maximal size of the critical region is 850 kb. Several human BAC clones have been isolated from the critical region by screening the Research Genetics human BAC library with STSs across the critical region. To date a partial contig has been constructed containing 8 BACs with 4 gaps yet to be filled. There are also 70 cosmids in the critical region, 48 of which have been mapped. Hybridization screens for transcription factors such as homeobox genes, which would have a high probability for involvement in VWS, have been negative to date.

16 genes which have been previously cytogenetically mapped to 1q32 have been excluded by testing for their presence on a somatic cell hybrid containing the microdeleted chromosome 1. Two genes mapped within the critical region but were excluded following extensive mutational analysis. A novel gene with homology to calmodulin dependent protien kinases was identified by sequence analysis of genomic subclones. This gene was also excluded by mutational analysis. Additional candidate screening is underway.