Laterality, Symmetry and Completeness Patterns of Nonsyndromic Orofacial Clefts in a Multiethnic Cohort

Abstract

ObjectiveNonsyndromic cleft lip with or without cleft palate (NSCL/P) presents in diverse phenotypic forms defined by laterality, symmetry, and completeness. This study examined these features and their associations with sex, race, and ethnicity in a multiethnic cohort of 3,561 individuals from North America, South America, Asia, and Africa. MethodsAssociations were evaluated using Chi-square or Fishers exact tests with Bonferroni correction. ResultsLeft unilateral clefts were the most prevalent, followed by right unilateral and bilateral clefts. The most common phenotype was a left complete unilateral cleft lip; the rarest was an asymmetric bilateral cleft with complete right-sided involvement. Among asymmetric bilateral cases, left-sided completeness was significantly more frequent than right-sided (p < 0.001), indicating the left side is both more commonly and more severely affected. Bilateral clefts -- both symmetric and asymmetric -- were more prevalent in males, while unilateral clefts were more common in females (p < 0.001). Asymmetric bilateral clefts occurred most frequently in Whites, whereas symmetric bilateral clefts were most common among Asians and Hispanics. Despite sex differences in bilateral cleft prevalence, completeness did not vary by sex for bilateral cases. For unilateral clefts, females showed higher completeness rates than males, and Asians and Hispanics/Latinos were more likely to exhibit complete unilateral clefts. Left unilateral clefts were most prevalent among Asians. ConclusionsSex, race, and ethnicity influence cleft laterality and symmetry, but cleft completeness appears sex-independent. The dissociation between side predominance and completeness suggests that distinct biological mechanisms govern cleft initiation and severity.