CLINICAL GENETICS OF CRANIOSYNOSTOSIS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。具体目的/目标概述：本研究是约翰霍普金斯医院、波士顿儿童医院、费城儿童医院和宾夕法尼亚州立大学的多学科团队合作联盟的一部分，对颅缝早闭患者进行全面的临床评价，以建立特征良好的先证者人群。颅缝早闭，一个或多个颅骨缝的过早融合，是一种复杂病因和发病机制的临床异质性疾病，发生率为1/2000活产婴儿。虽然有超过100种畸形综合征表现为颅缝早闭的主要表型特征，但大约85%的病例被认为是非综合征。在了解单基因综合征性颅缝早闭的临床和分子方面开始取得进展，非综合征性颅缝早闭（NSC）的特征是不完整的，很少有人知道的颅缝早闭头骨的人体测量轮廓。关于未被识别的颅内压（ICP）升高病例和高患病率的基亚里I畸形的报告表明，这些患者的临床护理可以得到改善。发育迟缓和/或学习障碍也存在于相当一部分患者人群中，认知结果与颅外异常、基因突变和特定人体测量参数直接相关。颅缝早闭的多器官系统受累和神经精神方面的特征也需要进一步研究。 对大量仔细分类的患者进行系统评价，将能够无偏地确定特定缝骨结合的临床和人体测量特征、基因型/表型变异性和特定发育基线特征。从特征良好的、临床同质的人群和一个样本中积累不同的数据集，

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Specific Aims/ Objectives General: This study is part of a collaborative consortium of multidisciplinary teams at the John Hopkins Hospital, Children's Hospital Boston, Children's Hospital of Philadelphia, and the Pennsylvania State University to perform comprehensive clinical evaluations of craniosynostosis patients in order to develop well-characterized proband population. Craniosynostosis, the premature fusion of one or more skull sutures, is a clinically heterogeneous condition of complex etiology and pathogenesis occurring in 1 out of 2,000 live births. While there are more than 100 dysmorphic syndromes that manifest craniosynostosis as a major phenotypic feature, approximately 85% of cases are believed to be nonsyndromic. Progress is beginning to be made in understanding the clinical and molecular aspects of monogenic syndromic craniosynostosis, the characterization of nonsyndromic craniosynostosis (NSC) is incomplete and little is known about the anthropometric profile of the craniosynostic skull. Reports of unrecognized cases of increased intracranial pressure (ICP) and a high prevalence of Chiari I malformation in metopic NSC patients suggest that the clinical care of these patients could be improved. Developmental delay and/or learning disabilities are also present in a significant portion of the patient population and cognitive outcome is directly associated with the extracranial anomalies, gene mutations, and the specific anthropometric parameter. Further characterization of multiple organ systems involvement and neuropsychiatric profile of craniosynostosis is also needed. The systematic evaluation of a large group of carefully categorized patients will allow the unbiased ascertainment of the clinical and anthropometric features of specific sutural synostosis, genotypic/phenotypic variability, and specific developmental baseline profiles. The accumulation of varied data sets from well-characterized, clinically homogeneous populations, and a specim