Detecting Birth Defects on the Horizon

Loeys Dietz syndrome may be diagnosable with blood test for specific protein levels

(RxWiki News) Doctors may soon be able to screen for a disorder with potentially fatal heart problems, giving doctors a better opportunity to immediately treat babies born with the condition.

People with Loeys-Dietz syndrome, also called Marfan syndrome type II, were found to have abnormally high levels of a protein called Transforming Growth Factor Beta, or TGF-β.

"Attend every prenatal appointment with your OB/GYN."

If doctors can develop a blood or tissue test to detect these levels in babies before or immediately after birth, they may be able to diagnose the condition much more quickly and begin appropriate treatment.

Junichi Iwata, a senior post-doctoral fellow from the Ostrow School of Dentistry at USC, led the study which gave them insights into the way the protein TGF-β interacts in the body and might cause Loeys-Dietz.

Babies born with Loeys-Dietz have abnormal facial features, including cleft palates, that are similar to other disorders, so doctors usually cannot make an immediate, accurate diagnosis.

Not diagnosing the problem quickly, however, can be fatal: children with Marfan syndrome type II usually have heart defects that can cause death if not treated.

"If we can screen patients for this, it can identify Loeys-Dietz syndrome and inform clinical practice," said co-author Yang Chai, director for the USC Center for Craniofacial Molecular Biology. "The prospects of this are very promising."
Iwata's team investigated the fetal development of mice and discovered mutations that cause TGF-β to communicate outside of cells in a way that might cause Loeys-Dietz syndrome.

The mutation prevents TGF-β from doing its various functions in a cell, including functions related to forming the facial palate.

The researchers suspected that TGF-β then tries a work-around to do its job, and when they activated the path they suspected it used, it led to the abnormal facial features seen in Loeys-Dietz patients.

A high level of TGF-β outside of a cell is an indicator that this mutation exist - and therefore that Loeys-Dietz may occur.

The researchers did not discuss how much it would cost to conduct screenings for Loeys-Dietz or whether there may be risks to the baby or mother.

The researchers also found that a reduction in TGF-β outside of the cell was able to prevent the facial defects from occurring before birth in the mice.

"In the longer term, our results could prove useful in efforts to identify safe and effective maternal nutritional and therapeutic interventions that reduce the risk of offspring developing these congenital malformations," the authors write. It's not known whether this ability to prevent the problem could work in humans.

The research appeared February 13 in the Journal of Clinical Investigation. It was funded by the National Institute of Dental and Craniofacial Research and the National Institutes of Health. The authors declared no conflicts of interest.