Sidedness in Unilateral Orofacial Clefts: A Systematic Scoping Review

Objective: An overview of the literature relating to the sidedness of unilateral cleft lip with or without cleft palate to map current knowledge on the cause and impact of directional asymmetry. Design: Scoping review with a systematic search of Medline and Embase from inception to May 2023. Patients, Participants: Humans born with a left or right unilateral cleft lip with or without a cleft palate. Main Outcome Measures: Cleft sidedness as a co-occurrence, an outcome or an exposure. Results: Forty studies were eligible for inclusion and confirmed the predilection for the occurrence of left sided cleft lips; 12 studies reported cleft sidedness co-occurring with another phenotype, 11 studies report sidedness as an outcome and 17 studies as an exposure. Phenotypes which were reported to co-occur with either left or right sided clefts included congenital dental anomalies, handedness and additional congenital anomalies. Variables investigated as a potential cause of left or right sided clefts as an outcome included chromosomal anomalies, genetic variants and environmental factors. Outcomes investigated in relation to cleft sidedness as an exposure included facial anatomical features, facial growth, educational attainment, functional and psychological characteristics. More studies showed worse outcomes in right sided clefts versus left sided clefts than vice versa, although studies were inconsistent, and a quality assessment was not performed. Conclusions: The field of cleft sidedness research is expanding and there are promising early findings to differentiate cause and outcome by sidedness of the cleft.