Genetic Associations with Pectus Excavatum: A Systematic Review

Area of Science:

• Genetics
• Medical Genetics
• Congenital Disorders

Background:

• Pectus excavatum (PE) is the most common congenital chest wall deformity.
• Familial clustering suggests a genetic basis for PE, but its molecular underpinnings are unclear.
• This review synthesizes genetic variant evidence to inform future research.

Purpose of the Study:

• To systematically review existing genetic evidence for pectus excavatum.
• To identify genetic variants and pathways associated with PE.
• To guide future genome-wide association studies (GWAS) and Mendelian randomization (MR) analyses.

Main Methods:

• A systematic search of electronic databases (Google Scholar, PubMed, Web of Science, arXiv) was performed.
• Nine studies meeting inclusion criteria were analyzed, focusing on genetic associations, family-based studies, or mechanistic investigations.
• Study quality was assessed using the Newcastle-Ottawa Scale.

Main Results:

• No population-level GWAS for isolated PE were identified.
• Fourteen genetic loci were reported across diverse study designs, implicating pathways in extracellular matrix, TGF-β signaling, cartilage development, and transcriptional regulation.
• Crucially, no SNP-level data (effect sizes, allele frequencies, odds ratios) were reported, preventing MR analyses.

Conclusions:

• Current genetic data for PE predominantly comes from rare variants and family studies.
• A significant gap exists due to the absence of population-level GWAS.
• Large-scale international GWAS are urgently required to identify common variants and elucidate PE's genetic architecture.