Developing 3D Craniofacial Morphometry Data and Tools to Transform Dysmorphology

描述（由申请人提供）：畸形形态学是儿科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。包括口面部畸形在内的1500多种综合征已被描述。今天，畸形学在很大程度上仍然是描述性的，诊断基于对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，在复杂三维（3D）形状的成像、量化和变异分析方面取得了巨大的技术进步，彻底改变了形态学变异的评估，允许定量形态学表型的强大定义，可以区分各种综合征的患者和对照组。本应用程序的目标是开发系统，使颅面三维形态测量学在临床实践中的诊断应用成为可能。我们的目的是定义特定的定量措施，表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3D形态测量面部扫描“库”，定义颅面畸形综合征，这是一个可以通过NIDCR FaceBase Hub与批准的研究人员共享的资源；开发三维几何形态测量（GM）和密集表面建模（DSM）分析工具，系统地分析和区分畸形综合征与未受影响的个体和彼此；最后，开发一个功能性的，自动化的，原型临床工具，能够同时区分大量的综合征，从而可以在临床环境中帮助实时诊断综合征。我们预计3D光形态测量“深度表型”，结合临床医学中外显子组和基因组测序的快速出现，将把畸形学从临床艺术转变为医学科学。

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.