Congenital Diaphragmatic Hernia Genetics and Signaling Pathways

Introduction to Congenital Diaphragmatic Hernia

The American Academy of Pediatrics notes that congenital diaphragmatic hernia occurs more commonly on the left posterior side of the diaphragm (85% left vs 15% right) and represents 95% of all congenital diaphragmatic hernias 1, 2.
The diaphragm normally forms and separates the thoracic cavity from the abdominal cavity during the eighth week of gestation, and congenital diaphragmatic hernia occurs due to incomplete development of the diaphragm 1, 2.

The World Health Organization acknowledges that alterations in FOG2, GATA4, or COUP-TFII interrupt the same molecular pathway, resulting in failure of mesenchymal development in the posterolateral region where these factors are critical 1, 2.
The National Institute of Child Health and Human Development states that no single genetic cause represents more than 1-2% of congenital diaphragmatic hernia cases, demonstrating high genetic heterogeneity 1, 2.

The American College of Medical Genetics recommends that genetic testing strategies can identify a genetic cause in up to ~30% of patients with non-isolated congenital diaphragmatic hernia 1, 2.
The European Society of Human Genetics notes that hypoplastic lung resulting from the presence of abdominal organs in the thoracic cavity during the prenatal period prevents or delays lung development, being the primary cause of morbidity and mortality 1, 2.