GENETIC FACTORS INVOLVED IN THE DEVELOPMENT OF CLEFT LIP AND/OR PALATE

Abstract

The etiology of cleft lip (CL) and/or cleft palate (CP) has been studied in the past decade and it seems to be heterogeneous and multifactorial, with a combination of both genetic and environmental risk factors. Epidemiological surveys have shown that CL and/or CP (CL/P) are among the most frequently observed birth defects in children. The advances in the field of genetics during the past decades have led to great improvements in the early diagnosis, intervention, prophilaxy and also therapy of various genetic disorders, including those involving the abnormal development of cranio- facial structures. Fogh-Andersen (1942) provided the first population-based evidence that OC has a strong genetic component. Since then, various linkage studies have suggested numerous loci could have a causal role in CL/P. Inconsistent results could be caused by the small size of the studies or genetic heterogeneity association studies. There are many roles of the genes that are involved in oral cleft: some genes function as growth factors (eg, TGF-α, TGF-β3), transcription factors (MSX1, IRF6, TBX22), or factors that play a part in xenobiotic metabolism (CYP1A1, GSTM1, NAT2), nutrient metabolism (MTHFR, RARA) or immune response (PVRL1, IRF6). The most intensively investigated genes have been the TGF-α and MTHFR genes. Although a large number of candidate gene studies have been conducted in this field, and several genome-wide association studies (GWAS) have recently provided more clues, specific causal variants and biological mechanisms responsible for occurrence of nonsyndromic cleft lip with or without cleft palate (NSCL/P) remain unclear

Keywords

• Genetics
• cleft lip
• palate
• genome-wide association studies (GWAS)