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

Area of Science:

• Craniofacial development and congenital anomalies.

Background:

• Orofacial clefts (OFC) are complex congenital conditions.
• A validated classification system categorizes OFC subphenotypes based on developmental timing (early/late) and mechanisms (fusion/differentiation).

Purpose of the Study:

• To investigate and define gender-specific differences in the prevalence of orofacial cleft (OFC) subphenotypes.
• To analyze these differences in a Dutch newborn population.

Main Methods:

• Retrospective cross-sectional study of 2089 children with OFC born between 2006 and 2016.
• Classification of clefts based on embryonic period (early, late, early/late), palate involvement (primary, secondary, primary/secondary), and defect type (fusion, differentiation).

Main Results:

• Females showed a higher prevalence of late-period (66% vs 55%) and secondary palate clefts (42% vs 23%).
• Males had a higher prevalence of early/late period (40% vs 27%) and primary/secondary palate clefts (44% vs 30%).
• Fusion defects were more common in females (60% vs 52%), while differentiation defects were more frequent in males.

Conclusions:

• Orofacial clefts in females are predominantly late-period, secondary palate, fusion defects.
• Orofacial clefts in males are more frequently early/late period, primary/secondary palate, differentiation defects.