Genetic epidemiology of cleft lip and palate: A review and potentials for Africa

Abstract

Orofacial clefts (CLP) are the most common congenital malformation of the craniofacial region with a world-wide prevalence of 1 in 700 births. They are usually classified into syndromic and non syndromic clefts and can be amongst the phenotypes seen in infants with multiple congenital malformations that can not be classified as a syndrome. While the genetic etiologies of syndromic clefts have been well characterized, the genetic etiology of non-syndromic clefts remains a challenge. However, with advances in the molecular genetic technologies and biostatistics tools that includes linkage and association studies, whole genome scanning and genome-wide association studies, candidate genes and loci in chromosomes with significant associations have been identified and validated. These include loci on chromosome 8q.24 and genes such as IRF6, MAFB and VAX1. Interestingly, all these genes were identified using populations of European and Asian ancestry. Considering that African populations are ancestral to European and Asian populations, genetic studies using predominantly African populations in Africa could provide particularly powerful insights into the origin of cleft lip and palate with the prediction that they would exhibit their own unique characteristics. The increasing pace of global genetic knowledge, and its applications for clinical medicine, as well as known geographic and genetic heterogeneity in non- syndromic cleft lip and palate (NSCLP) provides good scientific rational for the identification of new variants in African populations living in Africa.