Genetics of Nonsyndromic Cleft Lip and Palate: A Review of International Studies and Data regarding the Italian Population

Abstract

The aims of this review are (1) to illustrate current knowledge of the mode of inheritance and the loci involved in the cleft lip and palate and (2) to summarize the results of our investigations, which were carried out in Italy. It is well established that nonsyndromic cleft of the lip with or without the palate (CL±P) and cleft palate only (CPO) are separate entities. Genetic heterogeneity has been observed in CL±P, which involves different chromosome regions, mainly 6p23 (OFC1), 2q13 (OFC2), and 19q13.2 (OFC3), as well as other loci, such as 4q25-4q31.3 and 17q21. Furthermore, an interaction between different genes has been suggested in the oligogenic model. In one case at least, an OFC1 and OFC2 interaction has been demonstrated. The mode of inheritance of CPO is compatible with a recessive single major gene model, while an association with a candidate gene, mapping on the chromosome region 2q13/TGF α, remains to be confirmed.