Sturge-Weber Syndrome and Port-Wine Stain Birthmarks: Identifying the Cause, Pursuing the Cure

by Martie
Callaghan
November 13, 2013
Researchers at Kennedy Krieger recently announced the groundbreaking discovery of the genetic mutation that causes Sturge-Weber syndrome and port-wine stain birthmarks.

For patients with Sturge-Weber syndrome, like Madisynn Rodriguez (left), the discovery offers hope for new targeted therapies.After almost fifteen years of study, Anne Comi, MD, director of the Institute’s Hunter Nelson Sturge-Weber Center, and Jonathan Pevsner, PhD, director of Bioinformatics, confirmed their original hypothesis: the syndrome and the birthmark are caused by the same somatic mutation (an alteration in DNA that occurs after conception) now known to be in the GNAQ gene.

The discovery is important news for individuals and families affected by the syndrome, a neurological and skin disorder associated with the port-wine birthmark and with glaucoma, seizures, intellectual impairment, and weakness on one or both sides of the body. For the first time, parents can be assured that their child’s Sturge-Weber syndrome (SWS) was not caused by an injury sustained during pregnancy. “There is nothing the mother or the family did or did not do to cause SWS,” Dr. Comi says.

By establishing this genetic mutation as the cause of SWS, researchers also have proven that SWS is not an inherited condition. “We don’t know exactly why SWS happens in some individuals and not others,” Dr. Comi explains. “Somatic mutations occur at random throughout the lifetime of an individual in a localized area of the body. We think this particular alteration occurs in the first trimester of fetal development.”

Dr. Pevsner’s laboratory employed whole genome sequencing, a technology that allows examination of the billions of nucleotide pairs that form DNA, to identify the mutation. Affected tissue and unaffected tissue and blood samples from individuals with SWS were analyzed. Matt Shirley, then a graduate student in the Pevsner lab, was able to identify one somatic mutation common to affected samples.

Anne Comi, MD and Jonathan Pevsner, PhDThe study, published in May 2013 in the New England Journal of Medicine, represents a turning point, Dr. Pevsner says. “We suspected for decades that a somatic mutation was the cause of Sturge-Weber syndrome and port-wine birthmarks, but the technology to test that theory did not exist—until now. The advancements associated with whole genome sequencing and the development of next-generation sequencing tools finally allowed us to test and prove the hypothesis.”

Sturge-Weber syndrome is rare, affecting approximately one in 20,000 births, while port-wine stain birthmarks are more common, affecting approximately one million individuals in the United States. Current treatment options for children with SWS are limited, but include medications to reduce the likelihood of seizures and stroke-like episodes, eye drops or surgery to manage glaucoma, and physical rehabilitation.

With this new finding, much optimism surrounds future clinical trials. “We have real hope that in the next five to ten years—perhaps sooner, perhaps a little longer—there will be new treatments developed to inhibit the over-activation of those pathways,” Dr. Comi said. “We hope to move quickly toward targeted therapies, offering families the promise of new treatments for the first time.”

To learn more about current research initiatives at the Institute, visit kennedykrieger.org/research.