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Laterality and Completeness Patterns of Nonsyndromic Clefts in a Multiethnic Cohort

Spencer, C.; Machado-Paula, L.; Qian, F.; Butali, A.; Buxo, C. J.; Padilla, C.; Restrepo-Muneton, C.; Valencia-Ramirez, C.; Long, R. E.; Weinberg, S.; Marazita, M. L.; Murray, J. C.; Moreno-Uribe, L. M.; Petrin, A. L.

2025-12-29 genetic and genomic medicine
10.64898/2025.12.29.25343144 medRxiv
Show abstract

ObjectiveOrofacial clefts may involve the complete vertical thickness of the lip (complete) or partial thickness (incomplete). This study evaluates side preference for completeness in nonsyndromic asymmetric bilateral and unilateral cleft lip with or without cleft palate (NSCL/P). DesignWe studied 4 multiethnic cohorts from North and South America, Asia, and Africa, including 3,561 individuals with NSCL/P. Associations between cleft completeness, sex, ethnicity, and race were assessed using Chi-square or Fishers exact test (=0.05). ParticipantsPatients with NSCL/P with complete information on cleft type and completeness were included. Our main goal was to analyze side preference of complete clefting in different demographic groups, sex and race. ResultsAmongst asymmetric bilateral cases, left side completeness was significantly more frequent than the right side (73.7% vs. 26.3%; p<0.001). No associations observed for sex or race with ethnicity showing a trend toward significance (50.0% vs. 25.5%; p=0.088). Amongst symmetric bilateral and unilateral cases, Hispanics exhibited completeness more frequently than non-Hispanics (96.4% vs 89.5%; p<0.001; 84.1% vs. 79.7%; p<0.001). For unilateral cases, completeness showed no side preference. Caucasians were less likely to exhibit complete clefts compared to Asians, Blacks, or other racial groups (68.7% vs 84.9% or 81.2% or 81.7%; p<0.001). Females more frequently presented with completeness than males (81.2% vs 76.6%; p=0.003). ConclusionsIn NSCL/P with bilateral asymmetry, the left side is more often complete than the right side. Although unilateral left-sided clefts are more common overall, completeness shows no side preference. Race and ethnicity demonstrate significant associations with cleft severity patterns.

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