Genes and Pathways Associated with Skeletal Sagittal Malocclusions: A Systematic Review

Abstract

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.

Odontostomatological Traits in North-Eastern Italy’s Isolated Populations: An Epidemiological Cross-Sectional Study

“…The literature describes different patterns of skeletal classes’ distribution according to ethnicities: African and Caucasian populations show the highest prevalence of skeletal classes I and II, respectively, whereas Asians show the highest prevalence of class III, suggesting a genetic contribution to the malocclusions’ etiology [ 1 ]. To date, several genes (e.g., COL1A1 , FGFR2 , MATN1, and MYO1H ) and pathways (e.g., insulin receptor and FGFR2 signaling cascades) that are involved in craniofacial development have been identified [ 31 ]. However, due to the multifactorial etiology of malocclusions, more studies aimed at deepening the knowledge of the molecular and genetic mechanisms underlying their etiology are needed, with the final aim of better understanding these traits and developing personalized treatment strategies.…”

Does Sex, Skeletal Class and Mandibular Asymmetry Affect Tooth Length and Asymmetry in Tooth Length?

“…The authors intentionally did not include patients with skeletal class II in the study. It has been shown in the literature that there is a greater number of genetic factors influencing the development of skeletal class III than skeletal class II [25]. Moreover, there is ample evidence that genetic factors influence the length and anatomy of tooth roots [24].…”

The association of polymorphisms in BMP2/MYO1H and skeletal Class II div.1 maxillary and mandibular dimensions. A preliminary ‘report

“…Moreover, to the best of our knowledge this is the first genetic study that mainly involved subjects who presented with skeletal class II division 1 due to mandibular deficiency. We decided to evaluate SNPs in these specific genes because of their role in bone and cartilage growth and development and skeletal muscle maturation and construction ( Gershater et al, 2021 ).…”