Bresnick S, Schendel S
Department of Plastic and Reconstructive Surgery, LSPCH Medical Center at Stanford, Stanford University Medical Center, California 94305, USA.
J Craniofac Surg. 1995 May;6(3):245-8. doi: 10.1097/00001665-199505000-00012.
Reports have demonstrated that Crouzon's disease is associated with a gene on chromosome 10 coding for the fibroblastic growth factor (FGF) receptor 2. The purpose of this investigation was to evaluate the FGF receptor 2 levels in cranial sutures of children with Crouzon's disease and nonsyndromic, isolated craniosynostosis. Twelve children between the ages of 6 and 24 months were studied. Four patients had Crouzon's disease with coronal suture stenosis. The 8 remaining had a nonsyndromic, isolated coronal stenosis. Stenosed and adjacent nonstenosed cranial sutures were removed at cranioplasty and promptly fixed, decalcified, and embedded in paraffin. Immunohistochemical analysis of cranial sutures was performed with labeled, specific anti-FGF receptor 2 antibodies. In children with Crouzon's disease, we found significantly lower levels of FGF receptor 2 staining in stenosed sutures compared with nonstenosed sutures. In addition, sutures from children with Crouzon's disease demonstrated lower levels of FGF receptor 2 activity in both stenosed and nonstenosed sutures compared with children with a nonsyndromic, isolated coronal stenosis. However, there were no significant differences in FGF receptor 2 staining between stenosed and nonstenosed sutures in children with a nonsyndromic, isolated coronal stenosis. These findings suggest that low FGF receptor 2 activity in cranial sutures correlates with Crouzon's disease. This work supports genetic studies and yet shows that patients with Crouzon's disease have low FGF receptor 2 activity in cranial sutures. The findings also suggest that there may be etiological differences between syndrome- and nonsyndrome-associated craniosynostoses in children.
报告显示，克鲁宗病与10号染色体上一个编码成纤维细胞生长因子（FGF）受体2的基因有关。本研究的目的是评估克鲁宗病患儿和非综合征性孤立性颅缝早闭患儿颅缝中的FGF受体2水平。对12名6至24个月大的儿童进行了研究。4例患者患有伴有冠状缝狭窄的克鲁宗病。其余8例患有非综合征性孤立性冠状缝狭窄。在颅骨成形术时切除狭窄及相邻的非狭窄颅缝，并立即固定、脱钙，然后包埋于石蜡中。用标记的特异性抗FGF受体2抗体对颅缝进行免疫组织化学分析。在患有克鲁宗病的儿童中，我们发现狭窄缝中FGF受体2染色水平明显低于非狭窄缝。此外，与患有非综合征性孤立性冠状缝狭窄的儿童相比，患有克鲁宗病的儿童的狭窄缝和非狭窄缝中FGF受体2活性水平均较低。然而，在患有非综合征性孤立性冠状缝狭窄的儿童中，狭窄缝和非狭窄缝之间的FGF受体2染色没有显著差异。这些发现表明，颅缝中低FGF受体2活性与克鲁宗病相关。这项工作支持了基因研究，同时表明克鲁宗病患者颅缝中的FGF受体2活性较低。研究结果还表明，儿童综合征性和非综合征性相关颅缝早闭之间可能存在病因学差异。
