Causes of nonsyndromic craniosynostosis
The cause of nonsyndromic craniosynostosis is unknown. However, a number of theories have been suggested.
One theory is that nonsyndromic craniosynostosis may be caused by the baby adopting an unusual position in the womb. For example, if the baby’s head is pushed down by their mother’s ribcage, this will place pressure on their skull. This extra pressure may push the plates of bone together, causing the sutures in the skull to fuse too soon.
Another theory about what might cause nonsyndromic craniosynostosis is that a (as yet unidentified) defect in the cells that make up the suture causes them to fuse prematurely.
Most cases of syndromic craniosynostosis do not appear to be connected to anything that a mother does during pregnancy. An exception to this is women who take a medication called valproic acid (sodium valproate), which is used to treat epilepsy.
Research found that women who take valproic acid during pregnancy are seven times more likely to give birth to a child with craniosynostosis than women who do not take any medication. However, in general terms, due to the rarity of nonsyndromic craniosynostosis, this increase in risk is still very small – around one in 500.
Causes of syndromic craniosynostosis
Most cases of syndromic craniosynostosis are caused by one of four genetic mutations. A genetic mutation occurs when the instructions that are carried in certain genes (a unit of genetic material) become scrambled. This means that some of the body’s processes do not work in the normal way.
Examples of mutated genes are:
- FGFR1, FGFR2 and FGFR3 (three related genes)
- TWIST gene
The FGFR group of genes seem to make a protein called fibroblast growth factor receptor work less effectively. As this protein is involved in regulating cell growth, particularly the growth of bones, it is thought that the FGFR mutation disrupts the development of the skull.
The mutated TWIST gene seems to totally block the effects of fibroblast growth factor receptors, so birth defects that are associated with this gene are often wide-ranging.
