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Craniosynostosis: improving diagnosis and care for children with this rare condition

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What did the project achieve?

Our research has increased understanding of the causes of craniosynostosis and will help improve the diagnosis of the condition,” says Dr Stephen Twigg of the University of Oxford. “Receiving a precise diagnosis will enable more families to benefit from improved genetic counselling – and it may also help end a diagnostic odyssey that might have lasted years or decades, finally explaining what caused their child’s skull abnormality.”

Up to 350 children are born with craniosynostosis every year in the UK.1,2 In affected children, the bones in their skull fuse together too early, causing an abnormally shaped head and leaving no room for their brain to grow. Although a child can usually have operations to correct this, unfortunately, they can be left with some long-term problems.

“We already know that faults in multiple genes can cause craniosynostosis – which account for around one-quarter of affected children – but unfortunately, in many cases, we still can’t identify an exact genetic cause.”

This research involved examining the genetic material (DNA) of three known genes in 252 children with craniosynostosis – with a particular focus on surrounding ‘non-coding’ regions (sections of DNA surrounding, but not part of, the genes). Changes in these regions could be involved in development of the condition.

“Despite extensive searching, we found that changes in these non-coding regions of the selected genes do not make a large contribution to the condition,” says Dr Twigg. “This is important information as it increases understanding of how the disease is caused, and importantly, it will help doctors decide which parts of a child’s DNA to concentrate on to make a genetic diagnosis.”

The team successfully identified 14 faults in or very close to the three genes under investigation, most of which had not been picked up by routine screening.

“This is good news for these families as they can now receive improved genetic counselling,” says Dr Twigg. “In two children, we also found the first changes in a non-coding region lying close to the TWIST1 gene which causes Saethre-Chotzen syndrome – a type of craniosynostosis. This highlights the importance of screening this particular region of DNA in other families affected with this genetic syndrome who don’t yet have a precise diagnosis.”

 

References

  1. Headlines, http://www.headlines.org.uk/ [website accessed 05 August 2021]
  2. Wilkie AO et al. Prevalence and complications of single-gene and chromosomal disorders in craniosynostosis. Pediatrics 2010 126(2):e391-400.

This research was completed on

About 350 children are born with craniosynostosis every year in the UK.1,2 In children with this condition, the bones in the skull fuse together too early, giving the head an abnormal shape and leaving no room for the brain to grow. Children can usually have operations to correct this, but they can be left with some long-term problems. Dr Steve Twigg at the University of Oxford is looking at the genetic causes of craniosynostosis. He hopes this will help to diagnose the underlying cause of the condition earlier, giving families invaluable information, including a clearer picture of their child’s future. 

How are children’s lives affected now?

In babies and young children the skull is made up of several plates of bone. Between the plates there are narrow gaps that allow the skull to grow as the brain develops.

“Once the skull and brain are fully developed the gaps disappear and the plates fuse together” explains Dr Twigg. “In craniosynostosis, this happens too early.”

Children with the condition usually have surgery to correct head shape and make room for the brain to grow. But they can sometimes be left with vision or hearing problems, breathing difficulties or learning disabilities.

There are several genetic conditions linked to craniosynostosis, but in many cases the cause can be difficult to find.

“Parents often want to know what caused their child’s skull abnormality. In most cases a number of factors affecting the unborn baby are to blame, and in about a quarter of children a precise genetic diagnosis can be made through genetic screening” explains Dr Twigg. “But there are many affected children for whom the cause is still unknown.”

How could this research help?

A possible reason for why the cause remains unknown in some children may be that the fault sits in regions of the genetic material (DNA) that aren’t normally screened.

“These regions are called ‘non-coding’ DNA and they are the focus of our work” says Dr Twigg. The team plan to track down new causes of craniosynostosis in patients who do not yet have a specific genetic diagnosis by specifically looking at these regions of DNA.

“Finding the underlying genetic causes means that patients and families can immediately benefit from an accurate diagnosis, giving them a clearer picture of their child’s future” explains Dr Twigg. “This can end a diagnostic odyssey that could have lasted years or even decades.”

Their research could also help to guide surgical decisions and, in the longer term, lead to new treatment approaches.

References

  1. NHS Choices website http://www.nhs.uk/Conditions/Craniosynostosis/Pages/Introduction.aspx [accessed 29/08/2016]
  2. Wilkie AO et al. Prevalence and complications of single-gene and chromosomal disorders in craniosynostosis. Pediatrics 2010 126(2):e391-400

 

 

 

Project Leader Dr Stephen RF Twigg BSc DPhil
Project Team Professor Andrew OM Wilkie FRS FMedSci FRCPProfessor Jim R Hughes BSc DPhil
Project Location MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
Project Location Other MRC Haematology Unit, John Radcliffe Hospital, University of Oxford
Project duration 30 months
Date awarded 21 July 2016
Project start date 1 August 2016
Project end date 31 March 2019
Grant amount £173,162
Grant code GN2483

 

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