Developing 3D Craniofacial Morphometry Data and Tools to Transform Dysmorphology

描述(申请人提供)：畸形学是儿科学和临床遗传学的分支，与结构性出生缺陷和症状描述有关。包括口腔面部变形症在内的1500多种综合征已被描述。今天，畸形仍然在很大程度上是描述性的，诊断基于对面部和其他解剖特征的主观或半定量的临床印象。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的巨大技术进步使形态变异的评估发生了革命性的变化，使得定量形态计量学表型的可靠定义成为可能，可以区分各种综合征中的患者和对照组。这一应用程序的目标是开发能够在临床实践中实现颅面3D形态测量诊断应用的系统。我们的目标是定义具体的量化指标，以表征大量人类变形综合征中的异常面部形状。具体地说，我们的目标是建立一个广泛而深入的已定义颅面部变形综合征的3D形态测量面部扫描“库”，这是一个可通过NIDCR FaceBase Hub与经批准的研究人员共享的资源；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变形综合征与未受影响的个体以及彼此之间的差异；最后开发一个功能性、自动化、原型临床工具，能够同时区分大量的症状，从而有助于临床上对症状的实时诊断。我们预计，随着外显子组和基因组测序技术在临床医学中的迅速出现，3D光形态学“深度表型”将把畸形学从一门临床艺术转变为一门医学科学。

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.