Departmental Papers (Dental)

Document Type


Date of this Version


Publication Source

International Journal of Molecular Sciences





Start Page

Article number 13037




Skeletal class II and III malocclusions are craniofacial disorders that negatively impact people’s quality of life worldwide. Unfortunately, the growth patterns of skeletal malocclusions and their clinical correction prognoses are difficult to predict largely due to lack of knowledge of their precise etiology. Inspired by the strong inheritance pattern of a specific type of skeletal malocclusion, previous genome-wide association studies (GWAS) were reanalyzed, resulting in the identification of 19 skeletal class II malocclusion-associated and 53 skeletal class III malocclusion-associated genes. Functional enrichment of these genes created a signal pathway atlas in which most of the genes were associated with bone and cartilage growth and development, as expected, while some were characterized by functions related to skeletal muscle maturation and construction. Interestingly, several genes and enriched pathways are involved in both skeletal class II and III malocclusions, indicating the key regulatory effects of these genes and pathways in craniofacial development. There is no doubt that further investigation is necessary to validate these recognized genes’ and pathways’ specific function(s) related to maxillary and mandibular development. In summary, this systematic review provides initial insight on developing novel gene-based treatment strategies for skeletal malocclusions and paves the path for precision medicine where dental care providers can make an accurate prediction of the craniofacial growth of an individual patient based on his/her genetic profile. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.


Bone, Functional matrix theory, GWAS, Malocclusion, Mandibular prognathism, Mandibular retrognathism, Skeletal class II, Skeletal class III, SNP, Genome-Wide Association Study, Humans, Malocclusion, Mandible, Muscle, Skeletal, NFATC Transcription Factors, Phospholipase C gamma, Polymorphism, Single Nucleotide, Receptor, Fibroblast Growth Factor, Type 2, Signal Transduction, fibroblast growth factor receptor 2, phospholipase C gamma, transcription factor NFAT, bone development, bone growth, cartilage, craniofacial development, functional enrichment analysis, gene identification, genetic profile, genome-wide association study, human, malocclusion, personalized medicine, Review, signaling pathway analysis, skeletal sagittal malocclusion, skeleton malformation, systematic review, treatment planning, genetics, genome-wide association study, growth, development and aging, malocclusion, mandible, metabolism, pathology, signal transduction, single nucleotide polymorphism, skeletal muscle



Date Posted: 10 February 2023