Identification of a genetic cause for isolated unilateral coronal synostosis: a unique mutation in the fibroblast growth factor receptor 3

Abstract

To determine whether the autosomal dominant fibroblast growth factor receptor 3 (FGFR3) Pro250Arg mutation causes anterior plagiocephaly, patients with either apparently sporadic unicoronal synostosis (N = 37) or other forms of anterior plagiocephaly (N = 10) were studied for this mutation. Of 37 patients with unicoronal synostosis, 4 tested positive for the Pro250Arg mutation in FGFR3, and 33 were negative for this mutation. In three mutation positive patients with full parental studies, a parent with an extremely mild phenotype was found to carry the same mutation. None of the 6 patients with nonsynostotic plagiocephaly and none of the 4 patients with additional suture synostosis had the FGFR3 mutation. Because it is impossible to predict the FGFR3 Pro250Arg mutation status based on clinical examination alone, all patients with unicoronal synostosis should be tested for it. To assess their recurrence risk, all parents of mutation positive patients should be tested regardless of their clinical findings, because the phenotype can be extremely variable and without craniosynostosis.