Three genetic diseases studied

            BALTIMORE - Newswise noted at least three severe, potentially fatal genetic diseases leave patients with aortas so flimsy they can rupture in pregnancy and labor or even lesser activities, often without warning. Beta blockers, curbing exercise, proactive blood vessel surgery, and other approaches can be helpful, but their usefulness varies according to which disease and when they’re offered.

            Now, a follow-up study of more than 50 families by a multi-institutional team led by Johns Hopkins University scientists should bring better guidelines for treating the disorders. The work, published in the New England Journal of Medicine, closely compares patients having one of two types of the lesser known Loeys-Dietz syndrome or Ehlers-Danlos syndrome with better understood Marfan syndrome. It stresses the importance of comprehensive clinical evaluations when diagnosing the diseases.

            `People with Loeys-Dietz have wide-set eyes, a cleft palate, or split uvula (tissue that hangs down in the back of the throat), and a convoluted arrangement of the body's blood vessels, in addition to aggressive swelling of the aorta. In these patients, the aorta breaks at a much smaller size than it does in people with Marfan syndrome or most other causes of aortic aneurysm.

            Marfan and Ehlers-Danlos are similar heritable conditions with overlapping symptoms that affect the connective tissue, the tissue that holds the body together. Marfan can affect many body systems, including the skeleton, eyes, heart and blood vessels, nervous system, skin, and lungs. The vascular variant of Ehlers-Danlos also affects skin, muscles, and ligaments and causes hypermobility of joints and fragile blood vessels that tear easily.

            “This study shows clinical and molecular analyses can distinguish patients with Loeys-Dietz from those with either Marfan or vascular Ehlers-Danlos,” says Dr. Harry Dietz, director 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, 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 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, patients with Loeys-Dietz do much better with cardiovascular surgery, highlighting the importance of aggressive surgical intervention for this disorder.”