The birth prevalence of orofacial clefts (OFC) is about 17/10,000 live births and largely varies according to studies, ethnicity, location, socioeconomic status, and other factors. When using a conservative estimate of the population incidence of OFC (1 / 1,000 inhabitants), the world population of OFC is about 8.2 million. Most OFC (65%–70%) are nonsyndromic cleft lip and palate (NCLP) of multifactorial etiology.

Double helix discovery in the fifties and the Human Genome Project completed at the beginning of the 21st century meant moving from understanding the etiology of OFC based on epidemiology and family history characteristics to specific genes related to NCLP. Numerous genetic polymorphisms and loci have been identified in the present genomic era. It has been estimated that genetic mutations can explain only 20% of the etiology of NCLP. Thus, that part of multifactorial etiology – nonmodifiable factors presented by “candidate” or” susceptibility” genes was, and still is, a very active area of research in the etiology of OFC.

However, the other part of multifactorial etiology – non-genetic/environmental or modifiable factors and understanding epigenetics that handle their interactions with genetic ones – opens the window to cleft prevention. Thus, cleft prevention programs, protocols, awareness building, and educational activities must focus on modifiable, non-genetic, environmental, and epigenetic factors.

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