Aberrant bony vasculature associated with activating fibroblast growth factor receptor mutations accompanying Crouzon syndrome.
Aberrant bony vasculature associated with activating fibroblast growth factor receptor mutations accompanying Crouzon syndrome.
复制标题
异常的骨脉管系统与伴随克鲁宗综合征的成纤维细胞生长因子受体激活突变相关。
DOI：
10.1097/00001665-200405000-00016
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Ogle,RoyC
中科院分区：
文献类型：
--
作者：
Tholpady,SunilS;Abdelaal,MohamedM;Dufresne,CraigR;Gampper,ThomasJ;Lin,KantY;JaneSr,JohnA;Morgan,RaymondF;Ogle,RoyC
成纤维细胞生长因子受体突变与颅缝早闭综合征有关，事实上，也是引起颅缝早闭综合征的原因。这一知识导致了骨缝融合因果关系范式的转变;以前认为颅底异常张力导致穹窿骨缝融合，但现在认为发育中的颅骨异常细胞间信号传导导致骨缝形态发生异常。虽然与这些综合征相关的突变是已知的，表型的后果是有据可查的，从突变到表型的途径尚未阐明。手术重建是与颅缝早闭综合征（如Crouzon综合征）相关的颅面畸形的主要治疗方法。在许多情况下，颅骨穹隆的重塑取决于可用的自体骨的质量;然而，颅缝早闭综合征患者的骨通常比来自未受影响供体的颅骨更脆、更薄、更不坚固。综合征性颅缝早闭症与此骨之间的关系以前没有被描述过。在这项研究中，测量了Crouzon综合征患者和年龄和性别匹配的正常颅骨的骨单位和血管直径。统计分析表明，在血管直径，但不是在骨单位直径的定量和显着差异。这一发现可能是由成纤维细胞生长因子受体突变引起的异常血管发育的结果，该突变发生在骨形成之前并与骨形成同时发生，并导致骨组织变弱和脆弱。
Fibroblast growth factor receptor mutations are associated with and, in fact, cause most syndromes presenting with craniosynostosis. This knowledge has resulted in a shift in the paradigm of suture fusion causation; it was thought previously that abnormal tensional forces arising in the cranial base caused fusion of the vault sutures, but it is now understood that aberrant intercellular signaling in the developing skull leads to abnormal suture morphogenesis. Although the mutations associated with these syndromes are known and the phenotypic consequences are well documented, the pathway from mutation to phenotype has yet to be elucidated. Surgical reconstruction is the primary treatment of craniofacial abnormalities associated with craniosynostotic syndromes such as Crouzon syndrome. In many cases, calvarial vault reshaping is dependent on the quality of the autologous bone available; however, the bone of patients with craniosynostosis syndrome is often more brittle, thinner, and less robust than cranial bone from nonaffected donors. The relation between syndromic craniosynostoses and this bone has not been previously described. In this study, the osteon and blood vessel diameters of calvarial bone from patients with Crouzon syndrome and age-and sex-matched normal calvarial bone are measured. Statistical analysis demonstrates a quantitative and significant difference in the blood vessel diameter but not in the osteon diameter. This finding could be a result of abnormal blood vessel development caused by the fibroblast growth factor receptor mutation occurring before and coincident with bone formation and leading to weakened and fragile bone tissue.