Cleft lip and palate: understanding genetic and environmental influences

Clefts of the lip and/or palate are common and have a complex genetic and environmental basis. Recent work on these birth defects illustrates the value of combining genome-wide association studies, animal models and improved clinical phenotyping. Future work may also address gene–environment interactions. Clefts of the lip and/or palate (CLP) are common birth defects of complex aetiology. CLP can occur in isolation or as part of a broad range of chromosomal, Mendelian or teratogenic syndromes. Although there has been marked progress in identifying genetic and environmental triggers for syndromic CLP, the aetiology of the more common non-syndromic (isolated) forms remains poorly characterized. Recently, using a combination of epidemiology, careful phenotyping, genome-wide association studies and analysis of animal models, several distinct genetic and environmental risk factors have been identified and confirmed for non-syndromic CLP. These findings have advanced our understanding of developmental biology and created new opportunities for clinical translational research.