Embryologically Based Classification Specifies Gender Differences in the Prevalence of Orofacial Cleft Subphenotypes

Abstract

Background: A recently published validated classification system divides all orofacial cleft (OFC) subphenotypes into groups based on underlying developmental mechanisms, that is, fusion and differentiation, and their timing, that is, early and late periods, in embryogenesis of the primary and secondary palates. Aims: The aim of our study was to define gender differences in prevalence for all subphenotypes in newborns with OFC in the Netherlands. Methods: This was a retrospective cross-sectional study on children with OFC born from 2006 to 2016. Clefts were classified in early (E-), late (L-), and early/late (EL-) embryonic periods, in primary (P-), secondary (S-), and primary/secondary (PS-) palates, and further divided into fusion (F-), differentiation (D-), and fusion/differentiation (FD-) defects, respectively. Results: A total of 2089 OFC children were analyzed (1311 males and 778 females). Orofacial cleft subphenotypes in females occurred significantly more frequent in the L-period compared to males (66% vs 55%, P = .000), whereas clefts in males occurred significantly more in the EL-periods (40% vs 27%, P = .000). Females had significantly more S-palatal clefts (42% vs 23%, P = .000), while males had significantly more PS-palatal clefts (44% vs 30%, P = .000). Furthermore, the clefts in females were significantly more frequent the result of an F-defect (60% vs 52%, P = .000). Conclusions: Orofacial cleft in females mainly occur in the L-period are mostly S-palatal clefts, and are usually the result of an F-defect. Orofacial cleft in males more commonly occur in the EL-periods, are therefore more often combined PS-palatal clefts, and are more frequent D- and FD-defects.

The Efficacy of Curcumin Patch as an Adjuvant Therapeutic Agent in Managing Acute Orofacial Pain on the Post-Cleft Lip and Cleft Palate Surgery Patients: A Pragmatic Trial

“…The current study revealed that most of the participants were male participants. This finding is consistent with previous findings, 21 22 23 24 25 of which the male predominance in these types of birth defects was mainly reported. In a literature review by Mairaj et al, it was revealed that male predominance was reported for the prevalence of cleft lip and palate with a male/female sex ratio of 1.81 (CI 95%: 1.75–1.86).…”

Cleft Lip and/or Palate and Associated Risks in Lower-Middle-Income Countries: A Systematic Review

“…A study conducted in the Netherlands determined that CL/P was more common in males while cleft palate (CP) was more common in females (Pool et al, 2020). While one study concluded similar results (Bui et al, 2018a), other studies identified CL/P, CL, and/or CP to be more prevalent in females (Omo-Aghoja et al, 2010;Kalaskar et al, 2013;Mbuyi-Musanzayi et al, 2018;Ali & Hamid, 2019) and CLP, CL and alveolus, and CP to be prevalent in males (Mbuyi-Musanzayi et al, 2018;Ali & Hamid, 2019).…”

Seasonal Influence on the Numbers of Gender-Related Orofacial Cleft Conceptions in the Netherlands

“…Moreover, the impact of genetic variants on OFC risk for males and females differs (Carlson et al, 2018). Furthermore, Pool et al (2020) have recently found highly significant gender differences in the prevalence of OFC subphenotypes in the Netherlands. These data underline the fact that males and females must be assessed separately.…”

“…Additionally, the affected anatomical structures (lip, premaxilla/maxilla, hard palate, soft palate, and/or uvula), laterality, and the morphological feature of each anatomical structure (complete, incomplete, submucous, or hypoplasia) were noted, and any other head-neck anomalies with respect to soft tissues, tongue, nasal septum, ears, eyes, eyelids, and individual bones of the neurocranium and facial skeleton (Luijsterburg et al, 2014). This data set was previously used by Pool et al (2020). For data collection, the principles outlined in the Declaration of Helsinki were followed.…”

“…The following section describing the different subpenotypes is nearly identical to that in the article by Pool et al (2020), as the same data set was used, but different inclusion criteria were applied. To categorize the different cleft subphenotypes, the classification of Vermeij-Keers et al (2018) was used, distinguishing between early (4-7 weeks postconception) and late (7-12 weeks postconception) embryonic periods.…”