Laterality and Sidedness in Orofacial Clefts: Definitions and a Framework for Future Research

Area of Science:

• Craniofacial development
• Birth defects research
• Genetics and developmental biology

Background:

• Unilateral cleft lip (UCL) and cleft palate (CP) exhibit a consistent 2:1 left-sided predominance across diverse populations.
• Cleft sidedness has historically been viewed as a descriptive characteristic rather than a biologically significant indicator.
• Recent research shows growing interest in cleft laterality and its potential associations with morphological, developmental, and functional outcomes.

Purpose of the Study:

• To clarify terminology and address methodological challenges in cleft laterality research.
• To propose recommendations for future studies investigating the biological significance of cleft sidedness.
• To determine if cleft laterality reflects meaningful craniofacial developmental processes.

Main Methods:

• Literature review and synthesis of existing research on cleft lip and palate laterality.
• Analysis of inconsistencies in terminology, phenotypic grouping, and syndromic classification.
• Development of a framework for future research methodologies.

Main Results:

• Inconsistent terminology, phenotypic grouping, and classification methods complicate the interpretation of cleft laterality associations.
• These inconsistencies can alter cohort composition, influencing observed associations' magnitude and direction.
• A need for standardized approaches in cleft research is evident.

Conclusions:

• Cleft laterality, particularly the left-sided predominance in unilateral cleft lip/palate, warrants further investigation beyond mere description.
• Standardized research methodologies are crucial for uncovering the biological significance of cleft sidedness in craniofacial development.
• Future research should focus on resolving terminological and classification ambiguities to yield robust findings.