CLINICAL GENETICS OF CRANIOSYNOSTOSIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 具体目标/目标 总则：这项研究是约翰·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多学科团队合作的一部分，旨在对颅缝早闭患者进行全面的临床评估，以发展具有良好特征的先证者群体。颅缝融合，一条或多条颅缝过早融合，是一种临床上不同的疾病，病因和发病机制复杂，每2000名活产儿中就有一名发生。虽然有100多个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。对单基因综合征颅缝早闭的临床和分子方面的了解开始取得进展，非综合征颅缝早闭(NSC)的特征描述是不完整的，对颅缝早闭颅骨的人体测量学特征也知之甚少。有报道称，在异位NSC患者中，存在未被发现的颅内压升高和Chiari I型畸形的高发病例，这表明对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很大一部分患者中，认知结果与颅外畸形、基因突变和特定的人体测量参数直接相关。多器官系统受累的进一步特征和颅缝融合的神经精神病学特征也是必要的。对一大群仔细分类的患者进行系统评估，将使我们能够公正地确定特定缝合融合的临床和人体测量特征、基因/表型变异和特定发育基线特征。

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.