Craniosynotosis: Use Your Noggin

BY KRISTA CONGER

WINTER 2003 - The soft spots on a newborn baby's head can be a source of anxiety for new parents. But they are there for a good reason. The human brain triples in size during the first three years of life, and the skull must be able to expand to accommodate this growth.

If the spaces between the skull's boney plates grow together too soon, the child can suffer blindness, seizures, brain damage, and disfigurement. The only treatment is a long and complicated surgery to manually separate the bones and spread them apart.

"This is a big deal," says craniofacial surgeon and researcher Michael Longaker, M.D. "These kids are less than 1 year old, and there is invariably a lot of blood loss. It's very hard on a baby. But it's necessary to prevent serious complications and restore normal form."

Longaker is interested in identifying a less invasive, more appropriate way to treat the about 1 in 2000 infants who suffers from premature skull fusion.

"I wanted to know how we could do it fundamentally differently," he says, "by using biologically based therapies. Right now all we're doing is taking an abnormal piece of bone and changing its location in the skull."He began by studying the delicate dance of signaling molecules that tell the skull plates when and where to fuse, eventually homing in on a mouse protein called Noggin.

At 6 months of age, Creighton Morgenfeld had surgery at Packard Children's Hospital to correct a premature fusion of his skull's sagittal structure. Pediatric craniofacial surgeon Michael Longaker, M.D., FACS, and a team of researchers found that the absence of a protein called Noggin, which inhibits bone growth, is linked to premature skull plate fusion. By studying how Noggin works, clinical scientists may be able to develop less invasive ways to treat this relatively common condition in infants.

Although Noggin had been previously identified as an inhibitor of bone formation, no one knew how important it really was in skull growth until Longaker tested it in mice. He found that artificially prolonging Noggin expression in the skulls of the mice prevented fusion and left the animals with abnormally broad, squat heads -- sending Noggin to the head of the class, so to speak, in the school of molecules involved in skull fusion.

Noggin seems to work by hanging around in the spaces between the skull plates and repelling the efforts of other proteins that enhance bone growth. When the time is right for fusion, the body stops making Noggin and lets the other proteins take over.

Longaker envisions a time when small, time-release capsules of Noggin can be implanted in an infant's skull through very small incisions. Over the first few years of the child's life, Noggin would inhibit inappropriate bone growth, only to wear off in time for proper fusion to occur.

The concept has many challenges, including identifying the human form of Noggin and diagnosing infants at risk of premature skull fusion before their bones grow too tightly together.More sophisticated prenatal tests or the use of genetic markers may circumvent this problem. Longaker is unfazed by the difficulties facing the clinical scientist.

"Physicians always struggle with the clinical problems facing their patients," he says. "Ideally they lead a double-life in the lab that makes it easier for them to find new and better treatments for the kids they care for. If parents of these children were offered an opportunity to avoid this operation it would be fantastic for them. But it would be even better for their babies."