HETEROGENEITY IN CRANIOSYNOSTOSIS

颅缝过早融合的表型后果， 颅缝早闭，范围从微妙到明显的病因和 这种情况的发病机制是异质的。 基因基础 也被确定为涉及颅缝早闭的某些综合征 波士顿型颅缝早闭一家系。 如果 颅缝早闭是由调节发育的基因的变化引起的， 那么对出生后颅面发育的理解， 颅缝早闭症可以提供有关这一发病机制的信息， 条件下，并可能关于形态的产生， 分子水平。 该项目的重点是产后发育 孤立性颅缝早闭症的方面，特别是在三个 三维（3D）颅骨生长模式。 我们将系统地 存档所见患者的高分辨率计算机断层扫描（CT） 在大巴尔的摩地区。 两种孤立性颅缝早闭 最初的目标是冠状面和矢状面颅缝早闭 这些 选择这些组是因为它们相对较大（我们预计有20个 冠状和矢状17例/年），这些组不太可能 包括任何功能性骨结合。 因为每个颅缝早闭症患者 强调至少三项CT研究，这些临床指征 扫描最终将包括纵向数据库。 一个规范性 将使用未受影响的患者的CT扫描形成样本 颅缝早闭 以前的工作表明， 颅缝早闭可以通过分析生长模式来鉴别。 使用Richsmeier及其同事开发的形态测量方法， 将计算所有人的头骨的三维生长轨迹。 1例孤立性矢状面和孤立性冠状面骨性结合。 在每个 在这些诊断类别中，将进行聚类分析， 以便根据生长的相似性对个别病例进行分组 格局 我们认为，患者之间生长模式的差异 相似的形态学发现反映了基本的病因学和 病理生理差异。 3D生长模式的详细信息， 这些集群中的个体可以进行比较，以识别 一个集群所特有的增长模式。 我们定义的集群将是 根据标准数据计算的生长模式进行评价 从遗传学和流行病学方面收集的信息， 颅面发育中心的其他项目， 疾病，以进一步确定异质性的基础， 颅缝早闭

The phenotypic consequences of the premature fusion of cranial sutures, craniosynostosis, range from subtle to conspicuous and the etiology and pathogenesis of this condition is heterogeneous. A genetic basis has been determined for some syndromes that involve craniosynostosis as well as for a family affected with Boston type craniosynostosis. If craniosynostosis results from changes in genes regulating development, then an understanding of postnatal craniofacial development in craniosynostosis can provide information about the pathogenesis of this condition, and potentially about the generation of morphology at the molecular level. This project focuses on the postnatal developmental aspects of isolated craniosynostosis, specifically on the three dimensional (3D) growth pattern of the skull. We will systematically archive high resolution computed tomography (CT) scans of patients seen in the Greater Baltimore area. Two types of isolated craniosynostosis will be targeted initially; coronal and sagittal craniosynostosis. These groups are chosen because they are relatively large (we anticipate 20 coronal and 17 sagittal cases/year) and it is unlikely that these groups include any functional synostoses. Since each craniosynostosis patient underscores a minimum of three CT studies, these clinically indicated scans will eventually comprise a longitudinal data base. A normative sample will be formed using CT scans of patients unaffected by craniosynostosis. Previous work has demonstrated that classes of craniosynostosis can be differentiated by analysis of growth patterns. Using morphometric methods developed by Richsmeier and co-workers, three dimensional growth trajectories of the skull will be calculated for all case of isolated sagittal and isolated coronal synostosis. Within each of these diagnostic categories, a clustering analysis will be done in order to group individual cases on the basis of similarity in growth pattern. We propose that differences in growth pattern among patients with similar morphological findings reflect fundamental etiological and pathophysiologic differences. Details of the 3D growth patterns for individuals within these clusters can be compared to identify aspects of the growth pattern unique to a cluster. The clusters we define will be evaluated against the growth patterns calculated from the normative data and in terms of genetic and epidemiological information gathered from other projects within the Center for Craniofacial Development and Disorders in order to further define the basis for heterogeneity in craniosynostosis.