Facial Birthmarks Can Signal Deeper Problems in Brain
In the 1970s, some researchers recognized that facial hemangiomas like port-wine stain were associated with certain cerebrovascular anomalies. But it wasn't until 10 years ago that UCSF researcher Ilona Frieden, MD, and her colleagues recognized and described the association between facial hemangiomas and a wide variety of disorders like seizures, glaucoma, cardiac disorders, and various brain and cerebrovascular malformations.
They described the syndrome by the acronym PHACE because such large, segmental hemangiomas, most commonly of the face, were associated with one or more of the following anomalies: (P) posterior fossa brain malformations, (H) hemangiomas, (A) arterial anomalies, (C) coarctation of the aorta and cardiac defects, and (E) eye abnormalities. When ventral developmental defects - including (S) sternal clefting and supraumbilical raphe - are present, it is sometimes referred to as PHACES.
"In 1983, as a resident, I saw a patient with both a facial hemangioma and Dandy-Walker malformation (enlarged ventricles and a posterior cyst), and about 10 years later, I saw another patient who had the same thing," Frieden says. "I realized that even this was probably not a coincidence. We started looking around, and it turned out there had been many such cases, and still others - where hemangiomas were associated with cardiac and blood vessel abnormalities - which had been reported. The real advance in describing PHACE syndrome is that we were the first ones to 'connect the dots.'"
Since the group first described PHACE, the syndrome has become well recognized, and the presence of large facial hemangiomas has become a prompt for further investigation. One of Frieden's main projects now is to better define the risk of further malformations when hemangiomas are present.
She helped found the Hemangioma Investigator Group, which includes investigators in Milwaukee, New York City, Kansas City, Chicago, Cincinnati, Houston and Barcelona, Spain. This group works closely with the Birthmark and Vascular Anomalies Center at UCSF to better characterize the risks, and with the neuroradiology group to find the anomalies that may be present.
Hemangiomas signaling possible risk of further malformations are usually larger ones, Frieden says. "They are not just 'strawberries'; they typically cover an area of 20 square centimeters or more." Among children with facial hemangiomas of this size or larger, about 20 percent will have another of the defects described in PHACE syndrome. Ongoing studies are being performed to more accurately pinpoint the risk.
Since describing PHACE syndrome, Frieden and her colleagues have been investigating its origins. "Typically, 90 percent of the kids with PHACE syndrome are girls, and we don't know why," she says. They are currently collecting DNA samples from patients in an attempt to tie the syndrome to a gene or pattern of genes.
For more information, contact Dr. Frieden at (415) 353-7800.
This story originally appeared in the fall 2006 issue of Neuroscience at UCSF Medical Center.
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UCSF Medical Center
Ilona Frieden, MD
UCSF Birthmarks and Vascular Anomalities Center