Genetics of syndromic and nonsyndromic cleft lip and palate

Cleft of the lip with or without cleft palate (CL/P) represents one of the commonest congenital malformations in Western countries. Based on their association with specific malformative patterns or their presence as isolated defects, CL/P can be classified as syndromic and nonsyndromic, respectively. Both forms of CL/P are characterized by a strong genetic component. Syndromic forms are in many cases due to chromosomal aberrations or monogenic diseases. Among these, the Van der Woude syndrome, caused by mutation of the IRF6 gene, represents the commonest form of syndromic CL/P, accounting for about 2% of all cases. On the other hand, nonsyndromic CL/P is a multifactorial disease derived by the interaction between genetic and environmental factors. In recent years, great efforts have been made to identify the genes involved in the susceptibility to nonsyndromic CL/P and to disclose their relationship with specific environmental risk factors, to get information about the pathogenic mechanism leading to the malformation. In this article, we will review the most recent findings about the genes involved in the pathogenesis of syndromic and nonsyndromic CL/P, to provide information about the opportunity in the future to use specific genetic testing for the identification of at-risk mothers and the prevention of the disease based on a personalized approach.