Classification of oral clefts by affection site and laterality: a genotype-phenotype correlation study

Objectives – The aim of this study was to classify the phenotypes found in a series of patients with non‐syndromic cleft lip (CL) with or without cleft palate (CP) and isolated cleft palate. Additionally, the frequency distribution of cases belonging to families linked to markers on chromosomes 6 and 2 within these phenotypic patterns were estimated. Design – A retrospective examination of all the available affected cases collected in Italy. Setting and Sample Population – Ninety‐seven affected subjects aged 5–18 years belonging to 38 families were considered. Patterns were identified by variance of the cleft (lip, primary palate, secondary palate) and stratified according to the side of occurrence (right, left, or bilateral). Latent class analysis was used as main statistical tool for carrying out the results. Results – Three homogenous classes were identified (P < 0.0001) by means of latent class analysis. Individuals were assigned to the most suited class. All three variables (lip, primary and secondary cleft palate) generated a specific class. Optimal findings were reported in cases having `any isolated cleft lip' (class 1); `secondary CP with or without bilateral/right primary cleft palate + bilateral/right cleft lip' (class 2); and `left primary cleft palate + left/bilateral cleft lip with or without secondary CP' (class 3). Correspondence to the evidence of linkage to chromosome 6 showed that 9 of 10 cases presenting with `right primary CP + right CL with secondary cleft palate' (class 2) belonged to a linked family. The same combination, but occurring on the left side (class 3), revealed that only three of nine cases belong to families linked to chromosome 6 (P‐value=0.02). The two patterns (right and left) never occurred in the same family. Three reliable groups were identified based on laterality and the presence of a cleft. A single right sided pattern displayed a statistically different distribution of linkage to chromosome 6 when compared with the homologous left side. Conclusion – Non‐syndromic CL with/without CP can be classified according to laterality that can be under genetic control.