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Understanding and Treating Congenital Diaphragmatic Hernia

The diaphragm, a shelf of muscle that separates the chest cavity from the abdominal cavity, is critical to sustaining life. A life-threatening birth defect known as congenital diaphragmatic hernia (CDH), results from failure of normal diaphragm formation which in turn allows abdominal organs to migrate into the chest cavity. Abnormal lung development, so-called pulmonary hypoplasia, frequently co-occurs with CDH, and in fact is the major predictor of morbidity and mortality. This appears to arise from combined primary developmental defects of the lung, as well as mechanical compression from the displaced abdominal contents. CDH affects as many as 1 in 3,000 newborns and continues to have a mortality rate as high as 50 percent. Scientists have come to understand that it is not limited to a single or specific defect in the diaphragm and is often accompanied by other major malformations, usually relating to the lungs or cardiovascular development. There is also increasing evidence that genetic mutations in important developmental pathways contribute to CDH.

Four new reviews shed light on CHD by describing the diversity of the condition, exploring potential ways of treating it, using animal models to discover which genes play a role in diaphragm development, and examining its connection to cardiovascular malformations. The studies were published in May 2007 in a special issue of the American Journal of Medical Genetics Part C that examines the biology and genetics of CHD and is available online via Wiley InterScience at (http: www.interscience.wiley.com/journal/ajmgc).

In an introduction by Kate G. Ackerman and Barbara R. Pober of Harvard Medical School and several of the affiliated Harvard hospitals authors note that it is not known how many different types of diaphragm defects occur in humans or which types are developmentally related. They present a schematic developed to capture the full range of diaphragm defects which is currently in
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