Apert's syndrome correlates with low fibroblast growth factor receptor activity in stenosed cranial sutures.

Recent genetic studies have shown that Apert's syndrome results from mutations of the fibroblast growth factor (FGF) receptor 2 gene. We were interested in investigating the expression of FGF receptor 2 at the tissue level in children with Apert's syndrome. We studied FGF receptor activity in cranial sutures of children with Apert's syndrome and nonsyndromic, isolated craniosynostosis. Fourteen children between the ages of 6 months and 12 months were studied. Five of these children had Apert's syndrome with coronal suture stenosis. Nine children had an isolated, nonsyndromic coronal stenosis. Stenosed and nonstenosed cranial sutures were removed at the time of cranioplasty, fixed, decalcified, and paraffinized. Immunohistochemistry was performed with labeled, specific anti-FGR receptor 2 antibodies. We found lower levels of FGF receptor 2 staining in both stenosed and unstenosed sutures of children with Apert's syndrome compared with those from children with a nonsyndromic suture stenosis. Furthermore, fused sutures from children with Apert's syndrome demonstrated lower levels of FGF receptor 2 staining than unfused sutures from the same sample. The findings suggest that Apert's syndrome correlates with low FGF receptor 2 activity in cranial sutures. These results are consistent with and similar to our findings in Crouzon's syndrome, and support genetic studies showing localized mutational changes occurring at the FGF receptor 2 gene for both Apert's and Crouzon's syndromes. Furthermore, the findings suggest the possibility that variable expression of FGF receptor 2 occurs at the tissue level in patients with Apert's syndrome.