Cephalometric similarity among parents of individuals with sporadic isolated cleft palate: is there evidence for an inherited predisposition?

Abstract

Isolated cleft palate is one of the most frequent congenital conditions that affect the oral and facial structures, yet its etiology remains obscure. Previous studies of both cleft palate (CP) and cleft lip and/ or palate [CL(P)] have shown that there may be unusual facial characteristics among the parents of such sporadic cases. Such findings have been used to support the possibility that there are predisposing familial (genetic) factors for both conditions. However, previous studies have generally not controlled for the possibility of genetic heterogeneity or for different contributions from each of the parents. The objective of this study is to examine parents of individuals with CP in order to test the hypothesis that these "non cleft" individuals have abnormal facial structures. Lateral (LA) and Posterior-Anterior (PA) cephalograms were examined from thirty parents of fifteen individuals with sporadic CP. Seventeen LA and twenty-five PA variables were obtained on each subject and converted to standardized "z-scores" through comparison to published age and sex matched reference data. Multivariate cluster analysis was used to define groupings of individuals who shared similar patterns of facial features. Results demonstrate that as a group, relatives of CP individuals show significantly different patterns of facial measurements compared to reference norms. Values significantly larger (p < 0.05) fro1n parental data included: ANS-Me, PNS-ANS, S-N-Pg, Ar-Go-Me, MoL-MoR, NSR-NCR. Values significantly smaller (p < 0.05) from parents included: N-ANS, S-Ba, PNS-ANS/ N-ANS, PNS-ANS/ N-Pg, N-S-Ba, ZyL-ZyR, GoL-GoR, GoNL-GoNR, CRO-CNS, CNS-SD, CNS-Me, ID-Me, MxR-ZyR, Me-GoR. These findings were not entirely consistent with those few previously reported findings. Additional analysis of the present data demonstrated that such inconsistencies may be due in part to the presence of distinct phenotypic sub groupings within the parental sample. Cluster analysis identified two such subgroups. Significant findings (p < 0.05) that were smaller for Cluster 1 relative to Cluster 2 included: N-Me, ANS-Me, S-Go, PNS-ANS, Ar-Go, CNS-SD, MxR-ZyR. Significant variables that were larger for Cluster 1 included: S-N-Pg. In addition, gender was significantly different across clusters with Cluster 1 containing 75 percent female individuals and Cluster 2 containing 67 percent male individuals. These results extend those reported in other studies by demonstrating that unusual facial patterns, when present are not uniformly distributed in parents of sporadic cases of CP. Phenotypic assessment in conjunction with multivariate analysis may help to identify families in which there is a significant heritable component for CP.