A Yale-led consortium of researchers have identified genetic biomarkers for a significant percentage of a rare but often deadly malformation of blood vessels in the brains of infants, they report Dec. 18 in the journal Neuron.
The condition, called Vein of Galen malformation (VOGM), causes arteries that pump high-pressure blood to bypass the normal capillary system and instead funnel directly into veins, exposing them to abnormally high pressures. This can cause vessel rupture and brain hemorrhage in newborns.
“The effect is like trying to connect a your backyard garden hose to a fire hydrant — the veins simply cannot withstand such high pressures from pumping arteries,” said corresponding author Kristopher Kahle, assistant professor of neurosurgery, pediatrics, and cellular & molecular physiology.
The research team analyzed all of the genes of 55 children with VOGM and their parents. One of the mutations associated with increased risk that they identified is crucial to the development of the vascular system. Intriguingly, said the researchers, parents who carry mutations of this gene (EPHB4) also often had skin lesions as result of vascular irregularities.
This information about the parents might help doctors diagnose VOGM before infants suffer a brain hemorrhage, Kahle said.
Currently, the best treatment for VOGM is a minimally invasive endovascular procedure in which brain lesions are blocked by catheters guided into the brain. However, only a few facilities nationwide, including the Vascular Neurosurgery section at Yale New Haven Hospital led by Dr. Charles Matouk, a co-author on the study, have the capability of performing such procedures.
Kahle pointed out that existing drugs have been approved to treat other conditions caused by disruptions to genes linked to the cell signaling pathways identified in the current paper and may one day benefit young patients.
Yale’s Daniel Duran, now a neurosurgery resident in training, is the lead author of the paper. Former Yale geneticist Richard Lifton, now at Rockefeller University, and Murat Gunel, chair of neurosurgery, are key co-authors on the study.