Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Recognizing new aneurysm syndrome can save lives

01.02.2005


Physical traits, genetic test help with early diagnosis

A research team led by Johns Hopkins doctors has defined the physical traits and genetic basis of a new aortic aneurysm syndrome that is extremely aggressive and can cause death in early childhood. Early diagnosis of the syndrome and rapid surgical repair of the swollen aorta can save lives, the researchers report in the Jan. 30 advance online section of Nature Genetics.

Based on a review of medical records and experience with new patients, the Johns Hopkins team discovered that people with wide-set eyes, a cleft palate or split uvula (the tissue that hangs down in the back of the throat), and a torturous arrangement of the body’s blood vessels also have aggressive swelling of the aorta, the body’s biggest blood vessel. In these patients, the aorta breaks at a much smaller size than it does in people with Marfan syndrome or other causes of aneurysm, making identifying these patients critical, the researchers report.



"The severity of the physical traits can vary, but because the aorta ruptures so much sooner than one would expect, patients need to be identified and treated as early as possible and much sooner than is standard medical practice for other causes of aortic aneurysms," says Harry Dietz, M.D., 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.

The syndrome-defining traits can have a wide range of severity, and some other abnormalities, including congenital heart and brain defects and skeletal abnormalities such as early fusion of the bones of the skull or curvature of the spine, are seen in some patients. "It’s too soon to know how common or rare the syndrome might be," says Dietz, "but we know that surgery to fix the aneurysm works if patients are identified in time."

Sadly, one patient who came to the clinic with widely spaced eyes and aortic aneurysm died just a week after being evaluated. At the time of her death, her aneurysm had measured just 4 centimeters (about 1.5 inches) in diameter, and aneurysms in this part of the aorta usually aren’t repaired until they measure more than 5 centimeters (about 2 inches).

"It was incredibly unfortunate, but until this patient died we didn’t know that the rupture happened so much earlier than in any other condition," says Bart Loeys, M.D., an instructor in pediatrics and genetic medicine in the McKusick-Nathans Institute. "We can now get patients to surgery in time to prevent aortic rupture and save their lives."

The researchers suggest that doctors, particularly those at craniofacial clinics, consider requesting imaging studies to look for aortic aneurysm and abnormal blood vessel organization in patients with the syndrome’s physical traits, particularly widely spaced eyes, cleft palate or bifid (split) uvula or early fusion of the skull bones, a condition called craniosynostosis. "It’s surprising that a syndrome with this many outward features escaped notice until now," says Dietz, "but now that we know it exists, it’s critical that doctors look for it."

For example, the parents of an 18-month-old girl had brought her to the clinic because of a heart murmur caused by a connection between her lungs’ main blood vessel and the aorta.

"When I walked by a photo the girl’s mother sent for the 2003 holidays, it struck me that the girl’s eyes were just slightly wide-set," says Dietz. "We had just figured out the new syndrome, so I asked the girl’s local doctor to look in her mouth and tell me if she had a split uvula. The answer was yes. We found that the girl’s aorta was already approaching 4 centimeters, so we quickly scheduled surgery, and today she’s doing well."

The researchers also found the genetic mutations behind the syndrome, for which a diagnostic test is available at Johns Hopkins’ DNA Diagnostic Laboratory. The syndrome runs in families, but syndrome-causing mutations have also been found in patients whose parents were not affected.

All cases have had mutations in either the gene for transforming growth factor-beta (TGF-beta) receptor 1 or that for TGF-beta receptor 2, two halves of the receptor that binds TGF-beta. TGF-beta is a family of signaling molecules that controls cell growth, movement, activity and death by altering expression of many genes.

The researchers from Hopkins, Ghent University Hospital in Belgium and elsewhere are still trying to explain why the syndrome’s craniofacial traits can range from quite severe to barely noticeable, even though patients’ tortuous blood vessels and swollen aortas are disease hallmarks.

Those diagnosed with the new syndrome have arrived on Loeys’ and Dietz’s doorstep for a variety of reasons. One young patient was first seen because her aorta was wrapped around her esophagus, making it difficult to eat. An adult patient had been seeking medical evaluation because her father had died suddenly at age 29. Some others had been incorrectly diagnosed with Marfan syndrome and referred to Dietz’s well-known center. While there’s some overlap, Marfan syndrome’s outward physical traits are easily distinguished from those of the new syndrome.

"One case is a curiosity, two cases are intriguing," says Loeys. "But when you see 16 cases in 10 unrelated families, it shows that it’s real, particularly when there’s a family history that can be traced."

Mutations in the syndrome’s responsible genes had not previously been linked to the syndrome’s individual characteristics in people. The dozen or so mutations identified so far reduce the ability of the receptor to bind TGF-beta and transmit its signal, but that’s only indirectly the cause of the syndrome, Dietz suggests.

"We’ve found that too much TGF-beta signaling, not too little, is behind lung and heart valve problems in mice with the genetic defect behind Marfan syndrome, and we suspect the same in the new syndrome," says Dietz. "Our studies so far support the idea that these patients’ cells compensate for the problems in TGF-beta receptor 1 and 2, but in doing so overshoot what’s normal. More work needs to be done to address this issue, which might offer a target for developing medical intervention for these patients."

The Johns Hopkins researchers were funded by the Howard Hughes Medical Institute, the National Heart, Lung and Blood Institute, the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Marfan Foundation.

Authors on the paper are Loeys, Dietz, Junji Chen, Enid Neptune, Daniel Judge, Megan Podowski, Tammy Holm, Jennifer Meyers, Carmen Leitch, Nicholas Katsanis, Neda Sharifi, Lauren Xu, Loretha Myers, Philip Spevak and Duke Cameron of Johns Hopkins; Julie De Backer, Jan Hellemans, Paul Coucke and Anne De Paepe of Ghent University Hospital, Belgium; Yan Chen and Daniel Rifkin of New York University School of Medicine; Elaine Davis of McGill University, Montreal, Canada; Catherine Webb, Northwestern University School of Medicine; and Wolfram Kress, University of Wuerzburg, Germany.

Joanna Downer | EurekAlert!
Further information:
http://www.jhmi.edu
http://www.nature.com

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>