Developing 3D Craniofacial Morphometry Data and Tools to Transform Dysmorphology

描述（由申请人提供）：畸形学是儿科学和临床遗传学的分支，涉及结构性出生缺陷和综合征的描述。已经描述了超过1500种包括口面畸形的综合征。今天，畸形学在很大程度上仍然是描述性的，诊断基于面部和其他解剖特征的主观或半定量临床印象。在过去的十年中，显着的技术进步，成像，量化和复杂的三维（3D）形状的变化分析已经彻底改变了形态变化的评估，允许强大的定量形态表型的定义，可以区分患者从控制在各种综合征。该应用程序的目标是开发能够在临床实践中实现颅面3D形态测量学诊断应用的系统。我们的目标是定义特定的定量措施，其特征异常的面部形状在大量的人类畸形综合征。具体来说，我们的目标是建立一个广泛而深入的颅面畸形综合征的3D形态测量面部扫描“库”，该资源可以通过NIDCR FaceBase Hub与经批准的研究人员共享用于研究目的;开发3D几何形态测量（GM）和密集表面建模（DSM）分析工具，以系统地分析和区分畸形综合征与未受影响的个体以及彼此;最后，开发一种功能性的、自动化的、原型临床工具，其能够同时区分大量的综合征，从而能够在临床环境中辅助综合征的实时诊断。我们预计，3D光形态测量的“深度表型”，结合外显子组和基因组测序在临床医学中的快速出现，将畸形学从临床艺术转化为医学科学。

DESCRIPTION (provided by applicant): Dysmorphology is the branch of pediatrics and clinical genetics concerned with structural birth defects and delineation of syndromes. More than 1500 syndromes that include orofacial dysmorphia have been described. Today, dysmorphology remains largely descriptive, with diagnoses based on subjective or semi-quantitative clinical impressions of facial and other anatomic features. Over the past decade, dramatic technological advances in imaging, quantification, and analysis of variation in complex three-dimensional (3D) shape have revolutionized the assessment of morphologic variation, permitting robust definition of quantitative morphometric phenotypes that can distinguish patients from controls in a variety of syndromes. The goal of this application is to develop systems that will enable diagnostic application of craniofacial 3D morphometrics in clinical practice. We aim to define specific quantitative measures that characterize the aberrant facial shapes in a large number of human dysmorphic syndromes. Specifically, we aim to build a broad and deep 3D morphometric facial scan "library" of defined craniofacial dysmorphic syndromes, a resource that can be shared with approved investigators for research purposes via the NIDCR FaceBase Hub; to develop 3D geometric morphometric (GM) and dense surface modeling (DSM) analytical tools to systematically analyze and distinguish dysmorphic syndromes from unaffected individuals and from each other; and finally to develop a functional, automated, prototype clinical tool that is capable of simultaneously distinguishing a large number of syndromes, and that thereby can assist real-time diagnosis of syndromes in the clinical setting. We anticipate that 3D photomorphometric "deep-phenotyping", in conjunction with the rapid advent of exome and genome sequencing in clinical medicine, will transform dysmorphology from a clinical art into a medical science.