Eur J Pediatr. 2025 Nov 26;184(12):798. doi: 10.1007/s00431-025-06653-0.
ABSTRACT
Congenital diaphragmatic hernia (CDH), a rare defect (1/2000-1/4000 births), results from a diaphragmatic malformation allowing abdominal organs to invade the thorax. Despite progress in fetal and neonatal care, mortality reaches 30-40%, with survivors often facing chronic complications. Although chromosomal and monogenic anomalies suggest a genetic origin, CDH’s pathophysiology remains poorly understood and multifactorial. Omics technologies (genomics, transcriptomics, and proteomics) provide potentially powerful tools to decode its molecular mechanisms and discover predictive biomarkers for precision medicine. This review integrates well known genetic knowledge as well as recent omics advancements. Transcriptomics and proteomics uncover dysregulated pathways, microRNAs, and proteins linked to diaphragmatic development, its complications, such as pulmonary hypoplasia, and potential therapeutic targets.
CONCLUSION: Multi-omics integration highlights CDH’s complexity. Despite challenges like animal model limitations and biomarker accessibility, omics offers promising avenues-for prenatal counselling, risk stratification, and potential targeted therapies-ultimately improving clinical outcomes.
WHAT IS KNOWN: • CDH exhibits marked genetic heterogeneity, as it is associated with both chromosomal abnormalities and monogenic syndromes, yet no single gene explains more than 1-5% of cases. • High-throughput omics technologies in precision medicine have already identified therapeutic targets and helped better comprehension of pathophysiological mechanism.
WHAT IS NEW: • Multi-Omics integration in CDH research by combining genomics, transcriptomics, and proteomics uncovers dynamic mechanisms and therapeutic targets – such as miR-200b and STAT3 tested in animal models. • Proteomic and transcriptomic biomarkers in fetal biological fluids may enable to monitor prenatal therapeutic efficiency and perinatal outcomes.
PMID:41299117 | DOI:10.1007/s00431-025-06653-0
