Genetic susceptibility to orofacial clefts

Abstract

Background. Nonsyndromic oral clefts are some of the most common birth defects, affecting approximately one of every 600 births. Their etiology is not well understood but is thought to involve both genetic and environmental risk factors. Three studies were undertaken to explore the contributions of genetic and environmental risk factors and gene-environment and gene-gene interactions to oral cleft etiology. Methods. The three studies were: a systematic review of complex segregation analyses of nonsyndromic oral clefts; systematic reviews and meta-analyses on the role of folate in oral cleft etiology; and a case-parent triad analysis to investigate gene-environment and gene-gene interactions. Results and conclusions. Genetic and environmental factors were found to be involved in oral cleft etiology; gene-environment and gene-gene interactions were also found to be important. Studying interactions in addition to genetic and environmental factors alone may help to understand the etiology of these complex traits.