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Scientists Review Loeys-Dietz Syndrome in the Largest Ever Study to date

of the William S. Smilow Center for Marfan Syndrome Research at Johns Hopkins, professor in the McKusick-Nathans Institute of Genetic Medicine, and a Howard Hughes Medical Institute investigator, "Distinguishing these conditions is essential in many ways. For example, when compared to Marfan syndrome, Loeys-Dietz patients are at high risk of rupturing their blood vessels at smaller dimensions, at a younger age, and in a wider distribution throughout the body. They are also at a much greater risk of tear or rupture of blood vessels or the uterus during pregnancy. When compared to people with vascular Ehlers-Danlos syndrome, patients with Loeys-Dietz syndrome do much better with cardiovascular surgery, highlighting the importance of aggressive surgical intervention for this disorder."

"Because Loeys-Dietz shares so many symptoms with other conditions like Marfan or vascular Ehlers-Danlos, it's critical that diagnostic distinctions are made accurately."

The researchers gathered detailed information on patients' physical characteristics, their symptoms, course of disease and timing and effect of treatments. They also used gene analysis of the DNA sequences that encode for two proteins, the transforming growth factor-beta protein receptors type 1 (TGF-betaR1) and type 2 (TGF-betaR2). All cases of Loeys-Dietz studied so far have mutations in either TGF-betaR1 or TGF-betaR2.

The two TGF-beta receptors act together to bind TGF-beta, a family of signaling molecules that controls cell growth, movement, activity and death by controlling whether certain genes are turned on or off. TGF-beta receptors normally are found on the cell's surface, facing the outside of the cell, where TGF-beta can be found floating around.

The receptors contain specialized domains - dubbed kinase domains -- that, when bound by TGF-beta, add a chemical phosphate group to molecules that set in motion a domino-like effect within the cell to activate other chemical
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