HETEROGENEITY IN CRANIOSYNOSTOSIS

颅缝过早融合的表型后果， 颅骨融合症，从轻微到明显，病因和 这种疾病的发病机制是不同的。一种遗传基础是 也被确定为一些涉及颅缝早闭的综合征 至于一个受波士顿型颅缝早闭影响的家庭。如果 颅骨融合症是由调节发育的基因变化引起的， 然后对中国人出生后颅面发育的认识 颅缝融合可提供有关此病的发病机制的信息。 条件，并潜在地关于形态的产生 分子水平。该项目关注的是出生后的发展。 孤立性颅缝早闭的几个方面，特别是关于三个方面 头骨的三维(3D)生长模式。我们将系统地 将患者的高分辨率CT扫描存档 在大巴尔的摩地区。两种类型的孤立性颅缝融合 最初的目标是：冠状位和矢状位的颅缝早闭。这些 选择小组是因为他们相对较大(我们预计有20个 冠状位和17个矢状位病例/年)，这些群体不太可能 包括任何功能上的联会。因为每个颅骨融合症患者 强调至少三项CT研究，这些临床表明 扫描最终将包括一个纵向数据库。一种规范性的 样本将使用CT扫描形成不受影响的患者 颅骨融合症。以前的工作已经证明，类 颅缝融合症可通过分析生长方式加以鉴别。 使用Richsmeier和他的同事开发的形态测量方法，三 头骨的空间生长轨迹将被计算为 孤立性矢状面和孤立性冠状面融合1例。在每个 在这些诊断类别中，将在#年进行聚类分析 根据增长的相似性对个别病例进行分组的顺序 图案。我们认为，患者之间的生长模式差异 相似的形态学发现反映了根本的病因和 病理生理学差异。3D增长模式的详细信息 可以对这些集群中的个体进行比较，以识别 集群独有的增长模式。我们定义的集群将是 根据标准数据计算出的增长模式进行评估 在遗传和流行病学信息方面，从 颅面发育中心内的其他项目 紊乱，以进一步定义异质性的基础 颅骨融合症。

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.