PDF: Skeletal Class II Malocclusion: From Clinical Treatment to Genetic Insights with the Collaborative Cross Mouse Model

Skeletal Class II malocclusion remains one of the most prevalent and challenging dentofacial anomalies, often manifesting as mandibular retrusion, maxillary protrusion or a combination of both, with significant implications for facial aesthetics, occlusion, and overall oral health.

In their comprehensive article entitled “Skeletal Class II Malocclusion: From Clinical Treatment Strategies to the Roadmap in Identifying the Genetic Bases of Development in Humans with the Support of the Collaborative Cross Mouse Population”, Lone et al. present an integrative framework that bridges clinical orthodontic strategies and cutting-edge genetic research.

The paper begins by dissecting the heterogeneity inherent in Class II cases—highlighting skeletal-versus-dentoalveolar contributions, growth-stage considerations, and the spectrum of intervention options from early functional appliances to orthognathic surgery.

Importantly, the authors then pivot to exploring the genetic architecture underlying the skeletal Class II phenotype (SCIIMO), summarizing existing human linkage and association studies, emphasizing the gaps in robust heritability and gene-discovery data.

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Recognizing these limitations, the authors propose a novel roadmap: to leverage a genetically diverse murine platform—the Collaborative Cross mouse population (CC)—in parallel with large human cohorts, integrating genome-wide association studies (GWAS), epigenome-wide association studies (EWAS), RNA sequencing, and quantitative trait-locus (QTL) mapping.

This dual-track strategy aims to stratify and refine the phenotypic classification of Class II malocclusion, improve the power to detect novel genetic loci and modifiers, and translate molecular insights into early-detection and risk-stratification tools for orthodontic and surgical planning.

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For clinicians and researchers in orthodontics, dentofacial orthopedics and craniofacial genetics, this article offers a forward-looking blueprint: marrying established therapeutic paradigms with genomics and systems biology to unlock the etiological basis of a condition long treated empirically.

Its relevance spans from immediate clinical decision-making—identifying when growth modification, camouflage or surgery is indicated—to the aspirational horizon of personalized, genetics-informed treatment protocols.

👉 To explore the full article, including detailed treatment protocols, genetic analyses, proposed experimental workflows and rich tables/figures, please Review the PDF version available from the journal.