Molecular genetics of congenital diaphragmatic defects

Congenital diaphragmatic hernia (CDH) is a severe birth defect that is accompanied by malformations of the lung, heart, testis, and other organs. Patients with CDH may have any combination of these extradiaphragmatic defects, suggesting that CDH is often a manifestation of a global embryopathy. This review highlights recent advances in human and mouse genetics that have led to the identification of genes involved in CDH. These include genes for transcription factors, molecules involved in cell migration, and extracellular matrix components. The expression patterns of these genes in the developing embryo suggest that mesenchymal cell function is compromised in the diaphragm and other affected organs in patients with CDH. We discuss potential mechanisms underlying the seemingly random combination of diaphragmatic, pulmonary, cardiovascular, and gonadal defects in these patients.