Simeon Boyd, UC Davis professor of genetics and pediatrics, has received a nearly $4 million, five-year grant from the National Institute of Dental and Craniofacial Research to lead a team of physicians and scientists from more than 10 centers in the United States and seven international sites, including Australia, Brazil, Bulgaria, Germany, Hungary, Italy and the United Kingdom, to study craniosynostosis, the premature fusion of the bony plates of the skull in infants.
The researchers are members of the International Craniosynostosis Consortium, whose goal is to identify the genetic and environmental causes of craniosynostosis, which affects approximately 1 in 2,500 newborns worldwide, in order to find clues to prevention, better treatments, and eventually, a cure.
"Our goal is not only to identify the genetic causes of all types of craniosynostosis, but also to facilitate the early detection of the condition, by identifying biomarkers. This may allow for nonsurgical therapeutic intervention in utero in the future," said Boyd, who is a researcher affiliated with the UC Davis MIND Institute. The conditions also have neurodevelopmental consequences: Approximately 50 percent of patients with craniosynostosis also may have learning disabilities.
During fetal development, the skull is made up of separate bony plates that allow the child's head to grow after birth. The borders between the plates do not normally fuse completely until a child is about 2, leaving temporary soft spots at the intersections of the seams of the skull.
In craniosynostosis the bones fuse early, causing the child to have an abnormally shaped head. The disorder can lead to complications due to brain compression, such as visual problems and learning disabilities.
"This is not only a skull disease," Boyd said. "It is a perturbation of the brain and the skull, in which the growing brain is abnormal and causes increased distension of the envelope of the brain so that signaling molecules that normally would keep the sutures open do not function properly."
Depending upon the severity of the condition, children born with craniosynostosis frequently may require extensive neurosurgical intervention to separate the fused bones of the skull so that the child's brain can grow.
There are a number of different types of craniosynostosis, depending on which suture is prematurely fused. For example, when the sagittal suture at the top of the head is fused the condition is called in sagittal synostosis, also known as scaphocephaly. Sagittal synostosis is the most common form of the disorder. In coronal synostosis the coronal sutures, which run from the top of the head to the ears, are fused. Several named conditions, such as Muenke syndrome, have craniosynostosis among their symptoms.
In 2012, Boyd and his consortium colleagues published a landmark study in Nature Genetics, which found that two areas of the human genome are associated with a form of the disorder, sagittal craniosynostosis. Although the condition had long been believed to be partially determined by genes - it is three times more common in boys than in girls, and identical twins are much more likely to both be affected than fraternal twins - the genes associated with the disorder had not been previously identified.
Identification of the genetic basis for the conditions is only a first step in preventive and therapeutic strategies, Boyd said.
"We want to prevent babies from being born with these disorders," he said.
Consortium researchers from the United States include:
- Jon Bernstein, Stanford University
- Michael Cunningham, University of Washington
- John Graham, Cedars-Sinai
- Virginia Kimonis, UC Irvine
- Ophir Klein, UC San Francisco
- Pedro Sanchez-Lara, Children's Hospital Los Angeles
- Joan Richtsmeier, Pennsylvania State University
- Paul Romitti, University of Iowa
- Joan Stoler, Boston Children's Hospital
International Consortium researchers include:
- Andrew Wilkie, Oxford University, United Kingdom
- Wanda Lattanzi, Universita Cattolica del Sacro Cuore, Italy
- Tony Roscioli, University of Sidney, Australia
- Emil Simeonov and Radka Kaneva, Medical University, Sofia Bulgaria
- Bernd Wollnik, University of Cologne, Germany
- Eva Olah, University of Debrecen, Hungary
- Maria Rita Passos-Bueno, University of Sao Paolo, Brazil