Clinical and genetic studies of Van der Woude syndrome in Sweden

Van der Woude syndrome (VWS) is an autosomal dominant craniofacial disorder characterized by pits of the lower lip, hypodontia and cleft lip and/or cl eft palate. It has been reported as the most common form of syndromic orofa cial clefting with very high penetrance and varied expressivity. The diseas e locus for VWS has been mapped to chomosome 1q32, but the gene is yet to b e cloned. Here we report a total of 11 Swedish VWS patients: 9 familial cas es from two families and two belated cases. Clinical examination of these p atients showed phenotypic variability, even between patients from the same family. Genetic studies were performed using four microsatellite markers fr om chromosome 1q32. Constitutional deletion in this region was not demonstr ated in any of the familial or isolated cases. However, in the two VWS fami lies, linkage analysis using these markers showed positive LOD (logarithm o f the odds) scores ranging from 2.56 to 2.88 to all individual markers. The highest LOD score of 3.75 was obtained with the combined haplotypes of DIS 491 and D1S205, thus confirming linkage of VWS in these two families to 1q3 2. We conclude that there is varied expressivity but no evidence of genetic heterogeneity in VWS.