Decoding structural birth defects through genomic landscapes: Innovative frameworks for diagnosis (Review)

Structural birth defects (SBDs) represent a major subset of congenital malformations arising from abnormalities during organogenesis and subsequent tissue morphogenesis. The triad of congenital heart defects (CHDs), orofacial clefts (OFCs) and neural tube defects (NTDs) dominates the global epidemiology of SBDs, collectively contributing to considerable neonatal mortality while imposing profound clinical and socioeconomic burdens. Conventional genetic screening approaches, such as karyotype and non‑invasive prenatal testing, remain limited in their capacity to decipher the complex genomic factors underlying these SBDs. The advent of advanced genomic technologies (including chromosomal microarray analysis and next‑generation sequencing) and integrated genomic analysis methods [such as copy number variation analysis, single nucleotide variation/insertion and deletion analysis and genome‑wide association studies (GWAS)] has enhanced the capacity to identify pathogenic genetic factors, thereby transforming the mode of prenatal diagnosis and genetic counseling. The application of these technologies, by virtue of more accurate diagnosis and finer disease classification, not only provides a more comprehensive basis for assessing disease severity and prognosis in clinical decision‑making but also offers support for implementing targeted intervention and treatment. The present review systematically evaluates state‑of‑the‑art genomic methodologies and computational approaches for detecting genomic aberrations in CHDs, OFCs and NTDs, and integrates insights from GWAS to elucidate the underlying genetic architecture, contributing to achieving precise predictive modeling and targeted therapeutic innovation for SBDs.