Researching the Impact of Isolated Craniosynostosis

Dr. Matthew Speltz

Matthew Speltz is leading a
study into isolated

"The big question is whether isolated craniosynostosis — when only one of the sutures of the skull is fused at birth — causes developmental delays and whether the severity of the condition is related to the severity of the delays," says Dr. Michael Cunningham, medical director of Seattle Children's Craniofacial Center.

Dr. Cunningham is one of several Children's physicians and psychologists attempting to answer that question.

A National Institutes of Health (NIH) study led by Matthew Speltz, PhD, is following the mental development of 250 children with isolated craniosynostosis.

Each of the children in the study — which also involves medical centers in Chicago, St. Louis and Atlanta — is being compared to a child with a similar background from a control group.

The hypothesis is that children with isolated craniosynostosis are at greater risk of mild to moderate developmental delays, such as poor memory and learning disabilities.

Ours is the most comprehensive study to look at neurological development in children with isolated craniosynostosis.

Matthew Speltz, PhD

But that hypothesis is based on a handful of small studies, few of which included control groups.

"The difference with our study is its size and its use of a control group," says Speltz, who directs Children's Child Psychiatry Outpatient Clinic.

"Ours is the most comprehensive study ever to look at neurological development in children with isolated craniosynostosis."

The study involves multiple threads. One uses three-dimensional CT scanning technology to quantify skull shape and help determine whether there is a link between the severity of skull distortion and the degree of developmental delay.

Intuitively, it would appear there is a link, says Speltz, but it's also possible that the distortion and developmental delay are both caused by an unknown third factor. Another arm of the study is searching for the condition's genetic fingerprints.

Using bone samples from patients who've undergone surgery, Dr. Cunningham's laboratory has already found a link between simple craniosynostosis and novel mutations in a gene called TWIST, previously linked only to a syndromic form of craniosynostosis.

Craniosynostosis: Random or Inherited?

Isolated craniosynostosis has always seemed to strike randomly. Now, various clues are narrowing the search for the condition's possible causes.

Anne Hing

Olivia Bush's family history of unusual
head shapes inspired Dr. Anne Hing
(with Olivia and mom Cindy Bush) to
investigate whether simple
craniosynostosis is hereditary

One of those clues — that some family members of patients share the same unusual skull shapes — is driving a pilot study led by Dr. Anne Hing, a clinical geneticist at Children's Craniofacial Center.

Inspired by a patient, Olivia Bush, who has several relatives with craniosynostosis or similar unusual skull shapes, Hing reviewed the charts of 300 children treated at the Craniofacial Center and found that, in 6.5% of the families, one or more family members also had been diagnosed with craniosynostosis.

In addition, another 7% of families reported relatives with large foreheads or a long and narrow head shape. Isolated craniosynostosis is thought to occur when certain combinations of gene mutations and environmental factors interact.

Using 3-D photographic surface image technology, Hing is cataloging the head shapes of certain craniosynostosis patients and their parents to find patterns of inheritance.

After collecting data from Children's patients and parents, Hing will apply for an NIH grant to expand the study and seek genetic and environmental factors shared by patients with similar family histories

"We have a long ways to go," she says, "but you have to start by collecting some clues."