Molecular Genetics Of Pediatric Orofacial Clefts - An Overview

Abstract

Orofacial clefts (OFCs) are birth anomalies that occur frequently, affecting the lip and roof of the mouth. The complex etiology includes both genetic and environmental factors that influence their occurrence. OFCs are congenital malformations that are prevalent in the general population and affect the lip, palate, or both. A complex interplay between genetic and environmental factors leads to their development. This review intends to discuss the various molecular pathways involved in OFCs. Advances in genomic technologies have made significant strides in understanding the molecular basis of OFCs. Syndromic OFCs are associated with specific genetic mutations, such as TP63, IRF6, MSX1, and TBX22. Non-syndromic OFCs involve multiple genes and pathways, including PVRL1, FOXE1, MTHFR, and FGFR1. The WNT, TGF-beta, and FGF signaling pathways have also been implicated in OFC pathogenesis. Children with these defects are posed with significant speech, feeding, and hearing challenges, as well as an array of psychosocial problems which warrant multidisciplinary management. Unraveling the etiopathogenesis of the disease has paved the way for personalized medicine and opportunities to improve treatment modalities. An interdisciplinary approach between clinicians, geneticists, and researchers is pivotal in understanding the various aspects of  OFCs and in developing effective prevention and treatment protocols.