Genetic Factors Responsible for Cleft Lip and Palate

Abstract

Orofacial clefts (OFCs), including cleft lip (CL), cleft palate (CP), and cleft lip and palate (CLP), are one of the most common birth defects with an estimated prevalence of 1: 1000 live births. On the basis of association with other anomalies, OFCs can be classified as syndromic (30%) and nonsyndromic (70%). To date, the major causes of OFCs remain largely unknown. Chromosomal abnormalities, Mendelian single gene mutations, and teratogenic effects, as well as uncharacterized interactions between genetic and environmental factors are reported to be involved. Recently, various genetic approaches such as linkage analysis, case-control studies, genome-wide association studies (GWAS), candidate gene studies, and whole exome or whole genome sequencing have identified multiple genes/loci involved in the etiology of OFCs. Here, we briefly review the multiple genes/loci and molecular pathways that have been implicated in OFCs during the last few decades. The aim of this review is to provide a better understanding of the molecular pathogenesis of OFCs and to help with a more accurate diagnosis, genetic counseling, and personalized treatment decisions for better clinical care and prevention of OFCs.KeywordsCleft lipCleft palateOrofacial cleftsGeneticsMolecular pathways