Despite substantial efforts for the better half of a century, the detailed etiology of non-syndromic orofacial clefts remains largely unknown. The objective of this paper is to present an updated overview of the subject while introducing some essential terms and background information for the benefit of neophytes in the field of craniofacial studies.
Several genes have been investigated for a possible role in the pathogenesis of non-syndromic orofacial clefts; Some of these have been found to show association with the conditions, but none have yet proved to be decisive factors in their development. A recurring theme has been conflicting results from different studies; The main reasons for this are ethnic stratification of studied populations and the inherent complexity of the etiology itself, which is shown to contain both genetic and environmental elements.
A recent breakthrough is the identification of genes like TBX-22, PVRL-1, IRF-6 and MSX-1 as the culprits behind certain clefting syndromes; This discovery is made all the more interesting by the fact that other studies have implicated these genes in the pathogenesis of non-syndromal clefts as well. Environmental influences have also been investigated, and several studies show association between orofacial clefts and alcohol, smoking or anti-epileptic drugs. Certain combinations of genes and environmental factors have been shown to increase the relative risk of clefting; Such studies will undoubtly be an important part of future research. Current knowledge enables us to sketch out important principals and signal paths in the palatolabiogenesis, but a complete understanding of the molecular coordination that underpin these mechanisms remains to be established.