New insights into little known but common birth defect: Congenital diaphragmatic hernia

CDH is a common defect that occurs in 1 in 3,000 births, and 50 percent patients die from related complications. Research from the University of Utah provides new information on how CDH arises, opening avenues for researching therapeutic interventions. LEFT - The diaphragm acts as a barrier that separates the liver and guts in the abdominal cavity from the heart and lungs in the chest cavity. A normal, healthy diaphragm is comprised of a dome-shaped layer of muscle (red) that overlies a layer of connective tissue (green, not visible on left). CENTER – Experiments in mice show that diaphragms missing muscle do not develop hernias. RIGHT – Research suggests that CDH originates from regions with connective tissue but no diaphragm muscle. Internal pressure from growing organs in the abdominal cavity causes them to protrude through the weak spots and into the chest cavity.

Mar. 25, 2015 – Congenital diaphragmatic hernia (CDH) is not as well known as muscular dystrophy and cystic fibrosis, but like them it is a life-threatening birth defect, and is just as common. Occurring in one in 3,000 births, CDH causes the guts and liver to protrude through a defective diaphragm and into the chest cavity, where they interfere with the lungs.

Although many genetic mutations have been linked to CDH, a new study from the University of Utah School of Medicine is the first to demonstrate a linkage between genetic variation and a physiological mechanism that gives rise to defects in the diaphragm. The research points to a crucial role for connective tissue in CDH, and in guiding normal development of the diaphragm. These findings were published March 25, 2015, in Nature Genetics.

Research like this could tell physicians when and how CDH occurs in fetal development, opening the door to preventative treatments. “We learned that these defects happen really early – much earlier than previously thought,” says Gabrielle Kardon, Ph.D., associate professor of human genetics and principal investigator on the study. She stressed there are currently no therapeutic interventions to prevent CDH, and even with surgical patching of the diaphragms CDH is “silently killing half of the affected babies” – referring to the 50 percent mortality rate with this condition. Her lab is poised to test whether drugs can prevent the birth defect in animal models.