Orofacial clefts and face shape hypothesis. A brief review

Cleft lip and palate are common birth defects with complex aetiology, including a definite genetic component as well as environmental factors. Most cases are non-syndromic, meaning they are manifested as isolated deformities not associated with other anatomical or functional abnormalities. Due to the proven role of hereditary factors, parents and siblings of patients with cleft lip and palate run the genetic risk of passing the trait on to their offspring. Furthermore, both individuals with clefts and their unaffected relatives may exhibit distinctive minor facial features that set them apart from the rest of the population. Indeed, numerous studies have highlighted subtle differences in the faces of unaffected relatives from families with children with clefts compared to controls, and such differences have been interpreted as incomplete expression of an underlying genetic predisposition. Hence, these facial characteristics in the unaffected relatives can be seen as a subclinical phenotype and, for the same reason, as indicative of genetic susceptibility to cleft in the offspring of these subjects. The face shape hypothesis assumes that these facial features may constitute a liability factor for orofacial clefts, i.e. unaffected individuals tend to show a pattern in the facial shape that may indicate that they are genetically at risk for orofacial clefting. The most consistent features associated with this predisposition include upper facial width, increased interorbital width, decreased middle and upper facial height, increased lower facial height, and flattening of the facial profile resulting from a combination of excessive midface retrusion and mandibular protrusion. On the other hand, additional changes associated with a history of clefting may include a tendency towards a reduced width of the philtrum, slight alterations of the orbicularis labii muscle and the nasolabial area, as well as a whorled appearance of the lower lip. Thus, the aetiology of orofacial clefts could benefit from the study of these subclinical phenotypes. In this article, the embryological bases of lip and palate morphogenesis and the developmental pathogenesis of orofacial clefting are briefly reviewed, the concept of endophenotype is introduced, and a general discussion of facial changes associated with non-syndromic clefting is provided according to the face shape hypothesis, with possible implications of this topic as a tool for the study and prevention of these malformations.