Diseases

The diagnosis of aortic aneurysms, including those seen in the Loeys-Dietz syndrome, usually is made by injecting a dye that is visible by X-ray, computerized tomography (CT), or magnetic resonance imaging (MRI) into the blood vessels. X-rays or scans by CT or MRI then are done that show the arteries and aneurysms (because the aneurysms are filled with dye-containing blood). Although aortic aneurysms are the hallmark of Loeys-Dietz Syndrome and the characteristic facial features may suggest the diagnosis, the definitive diagnosis of Loeys-Dietz Syndrome can only be established by the genetic test (described above).

The only treatment for Loeys-Dietz syndrome to prolong life expectancy is surgical repair of the aortic aneurysm. Surgical repair of the aneurysms is generally successful. Since the aneurysms tend to rupture early, early and accurate diagnosis is critical to ensure that affected individuals receive prompt surgical treatment. The genetic test can be of value in identifying which individuals with aortic aneurysms have Loeys-Dietz syndrome, and therefore, should have immediate surgery. In contrast to Loeys-Dietz syndrome, in other inherited syndromes associated with aortic aneurysms, surgery carries a poorer prognosis, and the aneurysms can be managed with medications for a longer period of time before surgery becomes necessary. Studies are ongoing to determine whether drug treatment of the Loeys-Dietz syndrome also may be of value. At the time of diagnosis, imaging studies of the aorta are recommended and should be repeated after 6 months to determine if aortic enlargement is occurring. If the diameter of the aorta is not enlarging, yearly magnetic resonance imaging (MRI) scans from the of the circulation from the barin to the pelvis are recommended, since affected persons commonly develop aneurysms that are treatable surgically.

Loeys-Dietz syndrome is inherited, meaning that it is a genetic syndrome that tends to run in families. The mutated abnormal gene that causes Loeys-Dietz syndrome is dominant, and only one parent needs pass the gene to a child in order for the syndrome to develop. (This is in contrast to recessive syndromes in which each parent must pass the gene to a child in order for the syndrome to develop.) A report published in the New England Journal of Medicine in August, 2006, reported that 52 affected families (with a total of 90 affected individuals) had been identified.

Aortic aneurysms and abnormal organization of blood vessels (widespread tortuosity of the arteries in locations other than the aorta) are the hallmarks of Loeys-Dietz syndrome, but many affected children have characteristic physical and facial features that may be the first abnormality to be recognized. Recently, LDS has been subdivided into two types, LDS type I (LDSI) and type II (LDSII), signaling the presence or the absence of cranio-facial involvement, respectively. The craniofacial characteristics of Loeys-Dietz syndrome include early fusion of the skull bones (known as craniosynostosis), widely spaced eyes (hypertelorism), and cleft palate or split uvula. In some individuals with Loeys-Dietz syndrome, other physical abnormalities have been noted, including defects at birth in the heart and brain, osteoporosis (weak bones), skin changes (such as translucent skin and/or easy bruising), and defects of the spine or chest. It is important to note that the severity of the visible physical characteristics varies widely among affected individuals, but the danger of rupture of aneurysms remains the same no matter how severe or mild the physical characteristics are. In many cases pediatricians may be able to recognize the characteristic facial features of Loeys-Dietz syndrome, and on this basis suggest further evaluation for the presence of aortic aneurysms and vascular irregularities. Other people with the syndrome are recognized when they seek medical assistance for other reasons, such as heart murmurs or a family history of Marfan syndrome or another condition that may cause aortic aneurysms.

The cause of Loeys-Dietz syndrome has been determined recently. TGF-beta is a signaling molecule produced in the body that influences the growth, movement, and activity of cells as well as the death of cells by changing the way many genes within the cells are expressed. TGF-beta brings about the changes within cells by binding to receptors on the surfaces of the cells. . Loeys-Dietz syndrome is known to be a result of mutations in the TGF-beta-receptor I (TGFBR1) or II (TGFBR2) genes. The genetic mutations in Loeys-Dietz causes a change in the receptor that prevents TGF-beta from working on the cells. A test is available that can detect the genetic mutation associated with the syndrome; however, the test is not available in most laboratories.

Loeys-Dietz syndrome is a recently-described connective tissue disorder with features similar to those of Marfan syndrome, and the vascular type of Ehlers-Danlos syndrome. Loeys-Dietz syndrome is primarily characterized by aortic aneurysms (weakened outpouchings of the aorta, the main artery in the body) in children. In Loeys-Dietz syndrome, the aortic aneurysms are prone to rupture at a smaller size than other aneurysms, putting children with Loeys-Dietz at great risk for dying if the aneurysm is not identified and treated early. The syndrome is named for pediatric geneticist Harry Dietz, director of the William S. Smilow Center for Marfan Syndrome Research at Johns Hopkins University and his colleague, Bart Loeys, who characterized the genetic and physical markers of the syndrome together with Dr. Dietz.