The many faces and factors of orofacial clefts

Orofacial clefts are congenital structural anomalies of the lip and/or pala te that affect similar to 1/1000 live births. Their frequent occurrence as well as their extensive psychological, surgical, speech and dental involvem ent emphasize the importance of understanding the underlying causes, The et iology of orofacial clefts is complex, including multiple genetic and envir onmental factors. Rare forms, where they occur as one component of multiple congenital anomaly syndromes, have Mendelian or teratogenic origins; the n on-syndromic forms of orofacial clefts are more common and are likely due t o secondary gene-environment interactions. Recent advances in both molecula r and quantitative approaches have begun to identify the genes responsible for the rare syndromic forms of cleft and have also identified both candida te genes and loci for the more common and complex non-syndromic variants. A nimal models, in particular the mouse, have also contributed greatly to an understanding of these disorders. This review describes genes that are invo lved in orofacial clefts in humans and animal models and explores genetic a pproaches to identifying additional genes and gene-environment interactions that constitute the many factors of orofacial clefts.