Conditions

Genetic Cause of Port-Wine Stain Birthmarks, Sturge-Weber Syndrome Determined

Sturge-Weber syndrome - Port-wine stain birthmark genetic mutation
Sturge-Weber syndrome, in which individuals are born with port-wine stain birthmarks, is caused by a genetic mutation that occurs after conception in the GNAQ gene. Sturge-Weber UK

 

"Port-wine stain" birthmarks are caused by a genetic mutation that occurs after conception, reveals a new study, and that same somatic mutation is the key to the rare and potentially debilitating Sturge-Weber syndrome.

The findings, published on May 8 in the New England Journal of Medicine, are a "game changer" for people born with Sturge-Weber syndrome and port-wine stain birthmarks, said study co-author Dr. Anne Comi, Director of the Sturge-Weber Center at the Kennedy Krieger Institute, in a news release.

Researchers estimate that about one million people in the United States have port-wine stain birthmarks, reddish-purple skin discolorations caused by dilated capillaries that usually occur on the face and neck.

Healthy individuals can have such birthmarks, but children born with port-wine stains have a 6 percent chance of having Sturge-Weber syndrome, a neurological disorder that affects about one in every 20,000 newborn babies and is linked to glaucoma, seizures, learning disabilities, and muscle weakness.

There is no cure for Sturge-Weber syndrome, and current treatments can only manage symptoms with drugs that reduce seizures, surgeries for glaucoma, or physical rehabilitation for muscle paralysis.

"Now that we know the underlying genetic mutation responsible for both conditions," said Comi, "we're hopeful that we can move quickly towards targeted therapies, offering families the promise of new treatments for the first time."

Study co-author Dr. Jonathan Pevsner, also of the Kennedy Krieger Institute, found the genetic mutation by conducting whole-genome sequencing on tissues and blood samples from three people with Sturge-Weber syndrome.

The research team had long imagined that a somatic mutation, which is a DNA change that happens only after human sperm and egg cells meet during conception and can occur in specific patches of tissue, might be behind the rare disorder. They were unable to explore their suspicion, however, until new advances in genetic sequencing made it possible to do so.

Gene sequencing in Pevsner's lab revealed that DNA from all three samples shared a single somatic mutation, located in the gene GNAQ on chromosome 9q21.

They confirmed that result with genetic sequencing in a larger sample, finding the same GNAQ somatic mutation in the DNA of 23 out of 26 individuals with Sturge-Weber syndrome, and 12 out of 13 otherwise healthy people who had port-wine stain birthmarks. None of the healthy control subjects had that mutation.

Surprisingly to researchers, the GNAQ gene has also been pinpointed as a risk factor for uveal melanoma, a cancer that develops in the eye.

The results should reassure parents of children diagnosed with Sturge-Weber syndrome, said Comi in the news release- since the pivotal somatic mutation occurs after conception, the disease is not genetically inherited from parents.

Ultimately, the researchers hope their discovery of the GNAQ somatic mutation can lead to drugs that treat Sturge-Weber syndrome by inhibiting abnormal genetic activity. People with port-wine stain birthmarks and uveal melanoma might also benefit from such medications.

"This breakthrough gives renewed hope to my family and thousands of others," said Karen Ball, founder and CEO of the Sturge-Weber Foundation, in the news release, "and brings new opportunities to increase the pace of scientific discovery for Sturge-Weber."

Loading...