A Scoping Review on Genetic Mutations and Single-Nucleotide Polymorphisms Associated with Pectus Excavatum

Pectus excavatum (PE) is the most common congenital chest wall deformity, affecting approximately 1 in 400 live births, with a male predominance. While traditionally considered a primarily structural or biomechanical disorder, emerging evidence suggests significant genetic contributions to its etiology. This literature review systematically examines the current state of knowledge regarding genetic mutations, single-nucleotide polymorphisms (SNPs), and structural variants associated with pectus excavatum. A comprehensive search was conducted across multiple databases including PubMed, Google Scholar, SciSpace, and institutional repositories, yielding 14 relevant studies after de-duplication. The review reveals substantial genetic heterogeneity in PE, with identified variants predominantly affecting connective tissue genes including collagen family members (COL1A1, COL27A1, COL5A1), cartilage matrix proteins (ACAN, COMP), and signaling pathway components (SMAD4, REST). Copy number variants (CNVs), particularly the 3q29 deletion syndrome, show elevated PE prevalence. Early-onset PE demonstrates a 44% pathogenic genetic finding rate, suggesting stronger genetic contribution in childhood presentations. However, a critical gap exists in the literature: quantitative effect sizes such as odds ratios and hazard ratios are rarely reported, reflecting the predominance of case reports and small familial studies rather than large-scale genome-wide association studies. This review highlights the need for multi-center collaborative efforts to conduct adequately powered genetic epidemiological studies, establish genotype-phenotype correlations, and develop polygenic risk scores for clinical application.