Thanks to KU Leuven, we now have better understanding of the worldwide diversity in cranial shape, and how deformations occur

Peter Claes has successfully identified the genetic factor that accounts for the large variation in the shape of human skulls and faces, before subsequently identifying which of these genes play an important role in the risk of craniosynostosis, a condition where the fibrous sutures of a baby’s skull join together too early, preventing the skull from expanding as the brain develops and grows in the first two years of life. The results of the research are published today in Nature Communications.

When babies are born, their skulls have not yet fully fused together. As the brain continues to develop and grow during the first two years of life, elastic cartilage in the sutures allows the skull to expand along with it. But around 50 children are born every year in Belgium whose sutures join together too quickly, a condition called craniosynostosis. As their brains grow, certain parts of the skull cannot expand along, resulting in deformations of the skull and the face.

"Surgery is the only solution for these children. Fortunately, specialist doctors can successfully reconstruct the skull and face, but it is a highly invasive process for these young children," explains KU Leuven Professor of imaging genetics Peter Claes. "By gaining more insight into the genetics of the development of the brain, skull and face, we can better understand craniosynostosis. Understanding the underlying developmental processes can be the first step toward prevention, such as developing preventive drugs or changing environmental factors."

Large-scale study for worldwide conclusions

The study used a large dataset of 3D MRI images of nearly 7,000 children and adolescents, and compared the variation in skull and face shape with their DNA to identify which genes play a role in the processes of skull and face development. "Unlike other studies, we didn’t limit ourselves to a European population. Our findings are therefore less biased and our conclusions are more widely applicable at the global level," confirms PhD researcher Seppe Goovaerts.

Overlap between the development of the skull, face and brain

The study, published in Nature Communications, shows that there is significant overlap between the genes that play an important role in the growth and development of the skull and face as well as the brain. "But we all have a different appearance, so despite the fact that the same genes influence the processes, minimal genetic differences lead to significant variation in appearance and shape," Goovaerts explains. "Moreover, we noticed significant overlap between these genes and the mutations found in individuals with craniosynostosis. These processes are therefore all interrelated."

Advice for surgeons

"Since we mapped the variation in skull shape in our study, we could also advise surgeons in treating patients," Claes enthuses. "We can then simulate what the skull would have looked like if the sutures had not joined together. Surgeons can then use these images during operations to reconstruct the skull and face as accurately as possible. Furthermore, we can compare the reconstructed skull and face shape to our model of shape variation, and consequently provide objective feedback on the outcome."