Abstract

A recurrent point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene that converts proline 250 into arginine is commonly associated with coronal craniosynostosis and has allowed definition of a new syndrome on a molecular basis. Sixty-two patients with sporadic or familial forms of coronal craniosynostosis were investigated for the P250R FGFR3 mutation. It was identified in 20 probands originating from 27 unrelated families (74%), while only 6/35 sporadic cases (17%) harboured the mutation. In both familial and sporadic cases, females were significantly more severely affected than males. Hence, while 68% of females carrying the P250R mutation showed brachycephaly, only 35% of males had the same phenotype. In the most severe forms of the disease, the association of bicoronal craniosynostosis with hypertelorism and marked bulging of the temporal fossae were common hallmarks that might be helpful for clinical diagnosis.

Taken together, these results indicate that the P250R FGFR3 mutation is mostly familial and is associated with a more severe phenotype in females than in males. The sex related severity of the condition points to the possible implication of modifier genes in this syndrome.