RESEARCHERS in Oxford have discovered two new genetic causes of craniosynostosis – a rare bone condition that can inhibit brain growth in children.
The work will give affected families much greater understanding of the condition and inform patient treatment plans.
Andrew Wilkie, Nuffield Professor of Pathology at Oxford University and honorary consultant at Oxford University Hospitals NHS Trust, led the research published online in the journal Nature Genetics.
The study was supported by the Wellcome Trust, with additional funding from the National Institute for Health Research Oxford Biomedical Research Centre, a collaboration between the Oxford University Hospitals NHS Trust and Oxford University.
It was based on genetic data from more than 400 families treated at the specialist Craniofacial Unit at Oxford’s John Radcliffe Hospital over a twenty year period. Every gene in the family members’ DNA was sequenced in full at Oxford University, allowing the two new genetic causes of craniosynostosis to be identified.
About 1 in 2,200 children are born with craniosynostosis, a condition where the bony plates of the skull – known as sutures – are fused, leading to an abnormally shaped head. In some cases, the fusing of the sutures does not leave enough space for the growing brain which can increase pressure inside the skull, and can also cause hearing, vision and breathing difficulties.
About 21 per cent of craniosynostosis cases have a genetic diagnosis. The identification of two new genetic conditions takes that to about 24 per cent. The two new genetic conditions are each believed to account for one to two per cent of craniosynostosis cases.
Professor Wilkie said he believed that, in total, about 30 per cent of cases had a genetic cause, with the remaining 70 per cent partly attributable to a physical event during pregnancy.
The conditions with a genetic cause carry a risk of being inherited and, in most cases, are more severe forms of craniosynostosis.
Identifying a genetic cause, and then grouping together patients with the same underlying condition, allows medical staff to identify specific characteristics.
It gives individual families a greater understanding of the condition and allows treating consultants to be alert to potential future issues in an individual case.
A characteristic of the first new genetic condition – known as ERF – is that complications become apparent much later in childhood, at around age four of five, compared to the majority of craniosynostosis conditions which are apparent at, or shortly after, birth. Complications associated with the ERF gene then quickly become more serious if it is not recognised and treated.
In the second genetic condition – known as TCF12 – complications present almost immediately and require surgery. However, complications then tail off and most patients have a good long term prognosis.
Professor Wilkie said: “If consultants know the underlying genetic cause then they know what to look out for and they have a case management plan that is alert to the possible complications.
“It is about being fully aware of the condition, the characteristics, the cause and risks including the risk of it being inherited.”
Professor Wilkie, who in 1995 was the first to characterise Apert Syndrome (one of the most severe craniosynostosis conditions), said the collaboration of Oxford University researchers and NHS medical professionals ensured Oxford remained a world leading centre for research and treatment of the condition.
Professor Wilkie said: “There is a very close working relationship between surgeons, geneticists and the rest of the craniofacial team based at Oxford’s John Radcliffe Hospital. This is only possible within the NHS.”
“It is made possible by harnessing those strengths along with recent advances in genetics that allow us to sequence far more genes, more quickly.
“In the past couple of years, our team has discovered four new genetic conditions of craniosynostosis, and through ongoing research we are working on a further three.
“To put that in context, it is about equal to what the entire world effort has been able to describe in the past 20 years.”
The Craniofacial Unit at the John Radcliffe Hospital is one of four UK centres of excellence for the condition. The team worked in collaboration with colleagues at the other centres and the findings will be made available to all centres.