Fibroblast growth factor receptor 3 mutation in nonsyndromic coronal synostosis: clinical spectrum, prevalence, and surgical outcome

Object. A recurrent point mutation in the fibroblast growth factor receptor 3 gene that converts proline 250 into arginine has been reported recently in cases of apparently nonsyndromic coronal craniosynostosis. The goal of t he present study was to examine the phenotype of patients in whom this muta tion was present, to determine the prevalence of the condition, and to asse ss the functional and the morphological outcome of the surgically treated p atients. Methods. A DNA analysis was performed in 103 children suffering from appare ntly isolated coronal synostosis, 41 of whom had bilateral and 62 of whom h ad unilateral disease. There were 31 boys and 72 girls in the study group. Sixty cases were sporadic and 43 were familial; the 43 familial cases arose in 33 unrelated families. The mutation was found in seven (12%) of 60 spor adic cases and in 24 (73%) of the 33 families. The functional and morpholog ical results were assessed in all surgically treated patients who had at le ast 1 year of follow up and who were at least 3 years of age at the time of assessment. A comparison was made between patients with the mutation and t hose without. Conclusions. The most typical presentation was seen in girls and consisted of a bicoronal synostosis resulting in a severe brachycephaly associated wi th mild hypertelorism and marked bulging of the temporal fossae, which resu lted in a huge enlargement of the upper part of the face. The most frequent ly associated extracranial anomaly was brachydactyly, identified either cli nically or radiologically. Based on the proportion of bilateral and unilate ral coronal synostoses, the present data indicate that the mutation is asso ciated with more severe cases and that girls with the mutation are more sev erely affected than boys. The functional and morphological results were wor se in patients in whom the mutation was present as compared with those in w hom it was not.