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

Unilateral cleft lip with or without cleft palate demonstrates a consistent 2:1 left-sided predominance across populations. Despite this reproducible directional asymmetry, cleft sidedness has largely been considered descriptive rather than biologically informative. Growing interest in cleft laterality has prompted investigation into associations with morphological, developmental, and functional outcomes. Interpretation is complicated by inconsistent terminology, phenotypic grouping, syndromic classification, and handling of additional congenital anomalies, all of which may alter cohort composition and influence the magnitude or direction of observed associations. This position paper clarifies terminology, highlights methodological challenges, and proposes recommendations for future research to determine whether cleft laterality reflects biologically meaningful craniofacial developmental processes.