Current concepts on cleft lip and palate etiology.

Nonsyndromic cleft lip with or without cleft palate is the most common craniofacial anomaly affecting around 1 in 700 live births worldwide. Clefts of the human face can be classified anatomically as cleft palate only (CPO), cleft lip only (CLO), cleft lip and palate (CLP) or a combined group of cleft lip with or without cleft palate (CL/P), based on different in embryologic development. These malformations have some genetic origin, in fact several association studies have been performed to obtain important information about the candidate genes; but more important are gene-environment interactions that play an increasing role in its etiology. Epidemiological studies have shown how environmental factors (alcohol, smoking, drugs), as well as possible gene-environment interactions, play an important role in the onset of the malformation. On the contrary, folic acid intake seems to have a protective effect. In this review, we analyze the role of environmental factors related to onset of cleft.