Skeletal Class III phenotype: Link between animal models and human genetics: A scoping review

Abstract

This study aimed to identify evidence from animal studies examining genetic variants underlying maxillomandibular discrepancies resulting in a skeletal Class III (SCIII) malocclusion phenotype. Following the Manual for Evidence Synthesis of the JBI and the PRISMA extension for scoping reviews, a participant, concept, context question was formulated and systematic searches were executed in the PubMed, Scopus, WOS, Scielo, Open Gray, and Mednar databases. Of the 779 identified studies, 13 met the selection criteria and were included in the data extraction. The SCIII malocclusion phenotype was described as mandibular prognathism in the Danio rerio, Dicentrarchus labrax, and Equus africanus asinus models; and as maxillary deficiency in the Felis silvestris catus, Canis familiaris, Salmo trutta, and Mus musculus models. The identified genetic variants highlight the significance of BMP and TGF-β signaling. Their regulatory pathways and genetic interactions link them to cellular bone regulation events, particularly ossification regulation of postnatal cranial synchondroses. In conclusion, twenty genetic variants associated with the skeletal SCIII malocclusion phenotype were identified in animal models. Their interactions and regulatory pathways corroborate the role of these variants in bone growth, differentiation events, and ossification regulation of postnatal cranial synchondroses.