Touching Lives - December 2003
We all take special care when holding a tiny baby. This is partly because we know that babies’ heads are particularly vulnerable, as they are still ‘soft’ and the skull is still forming. In fact, skull growth continues until late adolescence, and its proper functioning is crucial.
But around 1 in every 2000 children is born with a genetic condition called craniosynostosis which prevents the skull from growing properly. While the number of children affected is relatively small, the effects of the condition are wide-ranging and potentially devastating.
In a version of the condition called Apert syndrome much of the skull is affected. Without surgery brain growth is restricted, causing serious mental defects. In other versions the skull growth malfunctions in some places and not others. In these cases, children may have normal intelligence, but they still have a seriously misshapen head and face. Having to contend with such a prominent physical abnormality can be very difficult for children and their families.
Currently, the only treatment is surgery, which starts early — from the age of three months to one year — and is inevitably serious and traumatic. And children who suffer from the condition may have to have several operations, since the process of bone growth continues to malfunction throughout childhood. But work done by Action Medical Researchers could mean the development of new treatments for the condition, reducing the number of operations these children have to endure.
What happens in craniosynostosis?
When we are born, the bones of the skull are still separate. In normal skull growth, new cells are formed at the very edge of the bone. As new cells form, the cells formed just before them stop dividing and make new bone.
To keep the skull growing properly throughout childhood, these two processes — the formation of new cells, and their conversion into bone — need to happen at a balanced rate. But in craniosynostosis bone forms too fast and new cells stop forming, so the skull bones fuse together prematurely and further growth is impossible, causing the various serious effects of the condition.
The genetic key
Craniosynostosis has been the focus of two Action Medical Research funded projects led by Gillian Morriss-Kay, Professor of Developmental Anatomy at the University of Oxford. Professor Morriss-Kay’s research aims to understand the underlying biology of the condition in order to develop other treatments in addition to surgery.
In the first project, which reported its findings in the summer of 2003, Professor Morriss-Kay and her colleagues looked at how certain genes affected in craniosynostosis control the balance between cell division and bone formation. They made some exciting and potentially life-changing discoveries about the condition.
In particular, Professor Morriss-Kay discovered that a specific gene is connected with growth at the edges of the skull bones. It is crucial in maintaining the balance needed for normal skull formation. However, in craniosynostosis the protein which keeps this gene ‘switched on’ is abnormal. Because of this, the gene is ‘switched off’ and the cells at the edges of the bones are converted into bone faster than new cells can be made, fusing the bones together prematurely.
Looking for an antibody
Professor Morriss-Kay’s research means that the aim of finding a non-surgical treatment, perhaps an antibody to target the abnormal protein, is now a step closer.
“Sadly, children with craniosynostosis will always need surgery of some description,” said Professor Morriss-Kay. “However, treatment with an antibody would mean that there wasn’t so much malformation to operate on in the first place. Also, there would be less abnormal growth after the operation, reducing the need for further surgery.”
Professor Morriss-Kay has seen the effect of this condition at first hand, and knows what a dramatic difference such a treatment could have on the lives of sufferers.
“Children seem to accept each other’s differences up to a certain age, but at around the age of six to eight they start noticing and pointing things out. We want to be able to prevent as much malformation in children affected by craniosynostosis as early as possible, minimising the physical and psychological damage caused by this condition.”