Dentoalveolar shape sariations in individuals with orofacial clefts and their unaffected relatives
Creators: name: Sarment, Lea
Publisher: name: University of Iowa
Year: 2025
Subjects: Cleft
Cleft Lip
Cleft Palate
Craniofacial anomalies
Geometric Morphometrics
public abstract

description: INTRODUCTION
description: The range of phenotypes present in patients with cleft lip and palate (CL/P) varies greatly in severity from abnormal craniofacial growth, dental anomalies, and malocclusion of the teeth and jaws. These variations can be associated to both genetic and environmental factors. Additionally, there may be physical sequelae from the surgical procedures and challenges to repair these clefts. It is important to understand the cleft-related phenotypic variations that may occur in unaffected family members (UFM) with whom cases presumably share genetic risk. An elevated risk for cleft-related anomalies in UFMs may shed light on the genetic factors that give rise to the anomalies rather than physical consequences from the surgical repairs. Many studies have compared facial shapes, dental morphologies, and cephalometric measurements for patients with orofacial clefts (OFC). This study aims to evaluate differences in 3D dento-alveolar shape between individuals with OFCs, their UFMs, and unrelated controls. Comprehending etiologic factors underlying such differences will aid with better management of these anomalies.
description: MATERIALS AND METHODS
description: Maxillary and mandibular digital casts were landmarked along the gingival margins, incisal edges, and cusp tips. There were a total of 1709 maxillary digital casts divided in UFM (n = 308) and controls (n = 729). Similarly, there were a total of 2085 mandibular digital casts including non-syndromic clefts (n = 111), their unaffected family members (UFM) (n = 621) and controls with no known family history of clefting (n = 1353). Given that orofacial clefts and scar tissue from their repair largely affect maxillary dentoalveolar shape, maxillary digital casts of individuals with clefts were not included in the shape analyses but only their mandibular casts. A 3-dimensional Procrustes fit was completed to scale all individual coordinate data sets followed by a canonical variate analysis to compare the dento-alveolar shapes between the study groups separately for maxilla and mandible. Mahalanobis and Procrustes distances were evaluated for the full data of 80 landmarks (first molar to first molar) and anterior data of 40 landmarks (canine to canine). Significance was determined with a 1,000-permutation test. Canonical variate results were visualized via wireframes to characterize the shapes differences between the groups. Further, Cases were divided by cleft type (cleft lip (CL), cleft lip and palate (CLP) and cleft palate only (CPO)) and laterality (unilateral or bilateral) and UFMs were divided by their family overall cleft type.
description: RESULTS
description: Shape differences were found between cases, controls, and UFMs using Mahalanobis and Procrustes distances for maxillary and mandibular datasets. The full dataset and anterior dataset of the maxillary data was divided into two comparisons: UFM vs. Control (Mahalanobis distances for the full and anterior dataset had P &lt;.0001, and Procrustes distance for the full and anterior dataset with P = .01) and UFM relative of CLP only vs. CP only vs. CL only (Mahalanobis distances for the full data set had P &lt; .0001, whereas all the other distances were not as significant.) The maxillas of UFM individuals separated themselves from those of controls due to the presence of Class III compensations, having proclined upper incisors, buccally rolled molars, reverse smile arcs, and narrow/tapered arch forms. The maxillary incisors also presented with a shape change resembling a possible Class III Collum angle. The UFMs separated by their family cleft type also showed unique characteristics, where the more severe clefts, CLP, had more Class III compensations.
description: The full dataset and anterior dataset of mandibular data was divided into separate comparison: Cases vs. UFM vs. Control (Procrustes and Mahalanobis distance P &lt;.0001, except the Procrustes value of UFM vs. Control full dataset with P == .015), CLP vs. CP vs.CL (Mahalanobis distance for the full dataset and anterior dataset P &lt;.0001, where all the Procrustes distances were less significant), and Unilateral cleft vs. Bilateral Cleft (Procrustes and Mahalanobis distance P &lt;.0001, except the Procrustes value of full dataset with P == .3130 and anterior dataset with P = .6050). In the mandibular data, the cleft cases were described to have Class III dento-alveolar compensations, with upright incisors, lingual rolled in molars, less arch projection, and more narrow and square arches. Cases also had shorter and wider teeth. The UFMs also had distinct differences from the controls, with Class III dento-alveolar compensations, shorter incisors, and large embrasures between the incisors. When comparing the cleft types, the more severe cleft anomalies, such as bilateral and CLP, had more significant Class III compensations.
description: CONCLUSIONS
description: There are significant differences in the maxillary and mandibular dento-alveolar shapes between individuals with clefts, UFMs who presumably have increased genetic cleft risk, and controls. The maxillary arches of the UFMs had distinct shape differences that were associated with Class III dento-alveolar compensations indicating that UFMs manifest distinct phenotypic variations likely due to their cleft risk when compared to the control population. Mandibular arches also presented with similar findings, where affected cases varied, and tended to have Class III dento-alveolar compensations and disproportionate width:height incisors. The mandibles of UFMs had more subtle changes but presented with similar phenotypic variations of Class III compensations and uniquely shaped incisors. As hypothesized, the UFMs, although not having an overt cleft, did have a spectrum of variation like cleft individuals. Additionally, more severe cleft types, bilateral clefts, and CLP, had more severe Class III compensations.