Michelle Li

A recent Yale study has identified the gene mutation for Vein of Galen malformation (VOGM) — a type of rare blood vessel abnormality inside the brain that is potentially fatal in newborns.

In a collaborative international effort with other pediatric neurosurgeons, the study collected the largest cohort of patients affected by VOGM. The researchers identified the gene mutations that account for VOGM, particularly pinpointing a gene called EPHB4. The study was published in the journal Neuron on Dec. 18.

“In VOGM, the intervening capillaries between the high-pressure arteries and the low-pressure veins [in the brain] are absent. This makes the veins susceptible to rupture and bleeding,” said Kristopher Kahle, professor of neurosurgery at the Yale School of Medicine and corresponding author of the study.

Kahle emphasized the severity of the disease, adding that if the disease is left untreated, the patients may die of catastrophic brain hemorrhage.

Since there is extremely limited knowledge of how a VOGM develops, the researchers hypothesized the involvement of a genetic component, which is found in other similar vein malformations.

The most fruitful way of getting patients to participate was the use of social media, particularly Facebook, Kahle noted.

“After extensive dealings with the Yale legal department, we were given permission to make posts on Facebook for different support groups to let people know about our study,” said Kahle.

He added that this grassroots level recruitment process empowered parents who have lost children to VOGM to get involved with the cause.

After the recruitment process, the researchers found that a few specific gene mutations can account for about 30 percent of all VOGM cases. In particular, the primary gene that results in VOGM developments is called EPHB4.

“The gene mutation that we have identified is part of a larger syndrome. In our study, we discovered that carriers of this mutation also exhibit splotch-like birthmarks in addition to VOGM,” said Daniel Duran, neurosurgery resident at University of Mississippi Medical Center and co-author of the study.

Duran added that sometimes carriers of the gene mutation develop skin splotches but do not have VOGM. He noted that the study also raises new questions about why some people with the identical genetic mutations develop the fatal VOGM condition while others do not.

According to Kahle, the potential implications of this study are far-reaching. The identification of the gene that causes VOGM can be useful for diagnostic screening.

“This study improves prenatal diagnosis by narrowing down a gene you can look for,” he said. “Knowing this is especially important, as treatment can begin before the vein rupture happens.”

Another important consequence of the study is that the mutated gene can be targeted with drugs. Kahle noted the existence of inhibitors approved by the Food and Drug Administration that can target this pathway.

Currently, Kahle and his team are in the process of creating an animal model to test whether the lesion can be reversed with drug treatment instead of neurosurgery or an endovascular treatment.

Ishana Aggarwal | ishana.aggarwal@yale.edu