Phenotypic diversity in white adults with moderate to severe Class III malocclusion

Introduction: Class III malocclusion is characterized by a composite of dentoskeletal patterns that lead to the forward positioning of the mandibular teeth in relation to the maxillary teeth and a concave profile. Environmental and genetic factors are associated with this condition, which affects 1% of the population in the United States and imposes significant esthetic and functional burdens on affected persons. The purpose of this study was to capture the phenotypic variation in a large sample of white adults with Class III malocclusion using multivariate reduction methods. Methods: Sixty-three lateral cephalometric variables were measured from the pretreatment records of 292 white subjects with Class II malocclusion (126 male, 166 female; ages, 16-57 years). Principal component analysis and cluster analysis were used to capture the phenotypic variation and identify the most homogeneous groups of subjects to reduce genetic heterogeneity. Results: Principal component analysis resulted in 6 principal components that accounted for 81.2% of the variation. The first 3 components represented variation in mandibular horizontal and vertical positions, maxillary horizontal position, and mandibular incisor angulation. The cluster model identified 5 distinct subphenotypes of Class III malocclusion. Conclusions: A spectrum of phenotypic definitions was obtained replicating results of previous studies and supporting the validity of these phenotypic measures in future research of the genetic and environmental etiologies of Class III malocclusion.