Kennedy Krieger researchers pinpoint cause of rare disease

Ida Heck is the mother of 8-year-old Jenna Heck, who has Sturge-Weber Syndrome.
Ida Heck is the mother of 8-year-old Jenna Heck, who has Sturge-Weber Syndrome. (Algerina Perna, Baltimore Sun)

It's a dream Ida Heck never really expected to come true.

Her family has raised about $1 million since 2005 for research into the rare disorder that afflicts her 8-year-old daughter, Jenna, resulting in cognitive deficits, seizures, long-lasting migraines, glaucoma in one eye and a red birthmark on the right side of her face.


She's been driven by a fervent hope that the money would help finance a breakthrough. Yet she had her doubts: "So often you give and give and give and never hear of any findings."

Then came this month's news from the Kennedy Krieger Institute in Baltimore. Researchers there announced that they had discovered the genetic mutation that causes both the disorder, Sturge-Weber syndrome, and the far more common port-wine birthmarks that don't harm the brain.


The researchers say this knowledge could lead to new treatments and, perhaps, one day, a cure. Dr. Anne Comi, a pediatric neurologist who has studied the disorder since the late 1990s, spoke directly to people like the Hecks in a video posted on Krieger's website.

"We have real hope in the next five to 10 years, perhaps sooner, perhaps a little longer, that there will be … new treatments and perhaps even a cure for Sturge-Weber syndrome," Comi said after summarizing the findings published recently in The New England Journal of Medicine.

Jenna Heck watched the video with her mother at their home in Davidsonville.

"Replay it," she told her mother.

The discovery — Comi calls it a "game changer" — owes a lot to tenacity and technology. Comi, 45, and molecular scientist Jonathan Pevsner, 51, have both been trying to unravel the mysteries of Sturge-Weber since attending a conference on the disorder in 1999. It's been dubbed an "orphan disease," one that attracts relatively little public attention or research money.

"We've been trying for many years to get at this," Comi said in an interview.

Scientists long suspected a genetic mutation that randomly occurred during fetal development. But "the technology didn't exist to fit that hypothesis, until now," said Pevsner, the study's co-senior author with Comi.

The technology that solved the puzzle, known as whole genome sequencing, allowed scientists to compare DNA in tissue affected by the disease with DNA in tissue that wasn't affected. That pinpointed the source as GNAQ, a gene well known to researchers and the subject of active research.

The mutation, which is not inherited, causes both the syndrome and port wine birthmarks, so named for their dark wine color.

Port wine birthmarks affect about 1 million people in the United States. One baby in 300 is born with such marks, which can appear anywhere on the body.

Sturge-Weber is much rarer, affecting about one in 20,000 babies. Only babies born with a port wine birthmark in the upper part of their face can develop Sturge-Weber. Those babies have a roughly 20 percent change of having the syndrome, though it's often not apparent for months whether that will turn out to be the case.

Abnormal capillaries under the skin cause the birthmarks. With Sturge-Weber, irregular blood vessels can also reach into the child's brain, blocking blood flow and depriving the tissue of oxygen and nutrients. As the brain shrinks and hardens, seizures, mental deficits and strokes can occur.


Current treatment options are limited, Comi said. For the birthmarks, laser treatment can lighten the mark, but the process frequently needs to be repeated over time.

For those with the brain effects, doctors use anti-convulsants to reduce seizures, but the treatment is not always effective. Studies have looked at using low-dose aspirin to aid seizure control and blood flow.

"This does help stabilize the patient and improve their seizure control," Comi said, "but it certainly is not the silver bullet we're looking for."

Comi said the basic shortcoming of existing treatments is this: "We were trying to treat symptoms without knowing about the cause."

Jenna Heck is among the patients Comi has long cared for as director of Krieger's Hunter Nelson Sturge-Weber Center. Comi said she has been "fairly stable" over the past couple years.

Ida Heck agreed, saying her daughter has not had to go to the hospital in three years. Medication controls the seizures, and her glaucoma, which has left her legally blind in her right eye, is deemed stable. She's now a third-grader receiving special education instruction in what her mother calls a mainstream classroom setting.

Her main challenge is migraine headaches that can last 10 days — and teasing. She's been slighted from attending birthday parties, her mother said. And one girl told her she would not sit next to her because "you look like a monster."

While the discovery of the syndrome's cause has no immediate impact on her daughter, Heck said it's both gratifying and encouraging. "It gives us a little more belief, a little more hope that a cure will come one day," she said.

She also hopes the finding will re-energize her annual fundraiser, Bands on the Bay, which has seen declining numbers in recent years.

The key discovery by the Krieger team occurred at the end of last summer in Pevsner's lab when a graduate student named Matthew Shirley made what Pevsner likened to finding a needle in a haystack. The finding was confirmed by analyzing dozens more tissue samples.

"For me it's a thrill," said Pevsner, the institute's director of bioinformatics. "As researchers, our dream is to make progress and make discoveries and hope they can impact people's lives."

Comi paused while searching for the right words to describe her feelings.

"There is a lot of satisfaction and also an eagerness to move forward — to take next steps," she said. "There's a lot of promise here, a lot of promise."

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