What gene change or mutation causes Crouzon syndrome?
Usually Crouzon is caused by a mutation in the FGFR2 gene. Everyone has two copies of the FGFR2 gene. The official name of this gene is "fibroblast growth factor receptor 2." This gene is located on chromosome 10. We get one FGFR2 gene from our mother and one FGFR2 gene from our father. Having a specific change (mutation) in one copy of the FGFR2 gene causes Crouzon syndrome.
In some cases, a specific mutation called p.Ala391Glu, p. A391G, or c.1172C>A in another gene called FGFR3 gene causes Crouzon syndrome together with a skin condition called acanthosis nigricans.
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How does having a mutation in a copy of the FGFR2 gene cause Crouzon syndrome?
The FGFR2 gene provides instructions for making a protein called "fibroblast growth factor receptor 2." This is a protein (building block) that is important for many processes in the body such as cell division, cell growth, wound heading, creation of blood vessels, and the development of a baby. This protein is located on the outside of our cells and communicates with other chemicals and proteins outside of the cell. This protein plays an important role in bone growth especially in the early stages. If the FGFR2 gene has a harmful change (mutation) in it, cell communication and overall bone development is disrupted, leading to the features seen in Crouzon syndrome.
Do all mutations in the FGFR2 gene cause Crouzon syndrome?
Not all mutations in the FGFR2 gene cause Crouzon syndrome. Mutations in the FGFR2 gene can also cause Apert syndrome, Beare-Stevenson cutis gyrata syndrome, Jackson-Weiss syndrome, lacrimo-auriculo-dento-digital syndrome, and Pfeiffer syndrome. Early fusion of the skull bones (craniosynostosis) is also seen in Apert syndrome, Beare-Stevenson cutis gyrata syndrome, Jackson-Weiss syndrome, and Pfeiffer syndrome.
If someone has a FGFR2 gene mutation associated with Crouzon syndrome, are they definitely going to be affected with the condition?
Almost all people with a FGFR2 gene mutation associated with Crouzon syndrome are affected with the condition (complete penetrance). There has been only one family report in which two children and a father had a FGFR2 gene mutation associated with Crouzon syndrome, but two of these family members were mildly affected and one family member was not affected at all.
- de Ravel TJ, Taylor IB, Van Oostveldt AJ, Fryns JP, Wilkie AO. A further mutation of the FGFR2 tyrosine kinase domain in mild Crouzon syndrome. Eur J Hum Genet. 2005;13:503-5. PMID: 15523492.
Are there any other gene mutations that cause Crouzon syndrome?
Only FGFR2 gene mutations are known to be associated with Crouzon syndrome. However, a specific mutation in the FGFR3 gene called p.Ala391Glu, p. A391G, or c.1172C>A causes Crouzon syndrome with acanthosis nigricans. Acanthosis nigricans is a skin condition where the folds and creases in the skin are dark colored (brown to black), thickened, and velvety.
- Mulliken JB, Steinberger D, Kunze S, Muller U. Molecular diagnosis of bilateral coronal synostosis. Plast Reconstr Surg. 1999;104:1603-15. PMID: 10541159.