Other features frequently associated with VWS include hypodontia in 10-81% of cases, narrow arched palate, congenital heart disease, heart murmur and cerebral abnormalities, syndactyly of the hands, polythelia, ankyloglossia, and adhesions between the upper and lower gum pads.

[4] Van der Woude syndrome is inherited as an autosomal dominant disease caused by a mutation in a single gene with equal distribution between the sexes.

[2] Due to the wide range of expressivity, it is also believed that other unidentified loci contribute to disease development.

The tyrosine in the normal protein at this position is conserved across mammals, frogs, and chickens, so despite the fact that it was a previously unreported mutation, it was expected to be deleterious.

Possible causes of phenotypic variability include variations in the intrauterine environment, epigenetic differences, or chance effects.

On day 32 of embryonic development there are four growth centers of the lower lip divided by two lateral grooves and one median.

The most common phenotype is two symmetrical lower lip pits flanking both sides of the midline in the bilateral paramedial sinuses.

The lip pits extend into the orbicularis oris muscle, ending in blind sacs surrounded by mucous glands.

[3] Clinical diagnosis based on orofacial clefts and lip pits typically occurs shortly after birth.

This form of CP may not be detected except through finger palpation, as the mucosa covering the palate is intact, but the muscles underneath have lost their proper attachments.

[7] Therefore, it is very important to closely examine these patients as well as their relatives for lip pits, especially when there is a family history of mixed clefting, in order to make the VWS diagnosis.

[3][4] The clinical signs seen in VWS are similar to those of popliteal pterygium syndrome (PPS), which is also an autosomal dominant disease.

[2] Genetic counseling for VWS involves discussion of disease transmission in the autosomal dominant manner and possibilities for penetrance and expression in offspring.