IDENTIFICATION OF A GENETIC CAUSE FOR ISOLATED UNILATERAL CORONAL SYNOSTOSIS - A UNIQUE MUTATION IN THE FIBROBLAST-GROWTH-FACTOR-RECEPTOR-3

To determine whether the autosomal dominant fibroblast growth factor r eceptor 3 (FGFR3) Pro250kg mutation causes anterior plagiocephaly, pat ients with either apparently sporadic unicoronal synostosis (N = 37) o r other forms of anterior plagiocephaly (N = 10) were studied for this mutation. Of 37 patients with unicoronal synostosis, 4 tested positiv e for the Pro250Arg mutation in FGFR3 and 33 were negative for this mu tation. In three mutation positive patients with full parental studies , a parent with an extremely mild phenotype was found to carry the sam e mutation. None of the 6 patients with nonsynostotic plagiocephaly an d none of the 4 patients with additional suture synostosis had the FGF R3 mutation. Because it is impossible to predict the FGFR3 Pro250Arg m utation status based on clinical examination alone, all patients with unicoronal synostosis should be tested for it. To assess their recurre nce risk, all parents of mutation positive patients should be tested r egardless of their clinical findings, because the phenotype can be ext remely variable and without craniosynostosis.