Folate related risk factors and orofacial clefting in human: epidemiological and biological studies

Abstract

Orofacial clefting (OFC) is a group of congenital malformations characterized by closure defects of the lip, jaw and/or palate. In general, three subgroups of OFC are distinguished, e.g., isolated clefts of the lip or the palate and clefts of the lip and the palate. Based on embryology, the isolated cleft of the lip and cleft lip together with cleft palate are considered a continuum of the same malformation, which will be referred to as cleft lip with or without palate (CL/P). This is in contrast to the isolated cleft palate (CP) which is regarded to be etiologically different. With a live birth prevalence rate of 11.8 per 10,000, CL/P is the third most frequent congenital malformation in The Netherlands [1]. This is more than twice as high as the birth prevalence rate of CP of 2.4 per 10,000 live births. Figure 1.1 shows the birth prevalence rates of CL/P and CP in the period from 1999 to 2008. Around 25% of the CL/P and 40% of the CP cases occur in combination with other malformations or as part of a syndrome and are considered syndromic clefts. In the studies presented in this thesis we focused on non-syndromic CL/P and CP that were not associated with other major congenital malformations.