Clinical Genetic and Morphometric Analysis of VCFS/DGS

描述(申请人提供)：Velo心面综合征和DiGeorge综合征是相对常见的疾病，至少影响4000名新生儿。大多数VCFS/DGS病例是散发性的。患有这些综合征的儿童表现出许多异常，包括面部畸形、心血管缺陷、免疫缺陷、言语缺陷和学习障碍。随着孩子们年龄的增长，他们中的许多人会患上严重的精神疾病。部分诊断为VCFS/DGS的患者在人类染色体22q11上有1.5或3.0Mb的DNA缺失。与VCFS/DGS相关的表型差异很大。同一家庭中携带相同缺失的个体有时会有不同的表型表现。由于表型谱的多样性，并不是所有的病例都是由22号染色体异常引起的，因此迫切需要制定VCFS/DGS诊断的定量临床标准。仔细的临床数据采集也可能使我们能够对患者群体进行分类和细分。VCFS/DGS患者的许多器官系统都起源于神经脊。这包括脸部。虽然公认面部畸形是VCFS/DGS表型的一个重要组成部分，但目前尚无良好的定量标准来描述面部畸形。我们建议使用一种新兴的三维摄影测量方法来收集临床诊断为VCFS/DGS患者的面部特征信息。这种方法是快速的，类似于拍照，并提供个人面部的数字化三维图像。由我们的同事编写并由我们应用的软件程序允许进行大量准确和可重复的测量。在三年的时间里，我们将招募300名患者参与研究，并从这些患者那里获得摄影测量数据和其他临床参数。我们假设面部特征可以作为这些综合征的准确诊断指标，并且它们将与缺失状态和缺失的大小相关。我们已经召集了一组临床和基础科学家以及一名生物信息学家来解决这个问题。

DESCRIPTION (provided by applicant): Velo-cardio-facial syndrome and DiGeorge syndrome are relatively common disorders and affect at least 1/4000 newborn children. Most of the cases of VCFS/DGS are sporadic. Children with these syndromes present with a number of abnormalities including facial dysmorphology, cardiovascular defects, immune defects, speech defects and learning disabilities. As the children grow older, many of them develop severe psychiatric illness. A subset of the patients diagnosed to have VCFS/DGS have a deletion of either 1.5 or 3.0 Mb of DNA on human chromosome 22ql 1. The phenotypes associated with VCFS/DGS are quite variable. Individuals within the same family who carry the same deletion sometimes have different phenotypic manifestations. Because of the variability in the phenotypic spectrum and since not all cases may result from abnormalities in chromosome 22 there is a strong need to develop quantitative clinical criteria for VCFS/DGS diagnosis. It is also possible that a careful clinical data acquisition would allow us to classify and sub classify the patient population. Many of the organs systems affected in VCFS/DGS patients have their origin in the neural crest. This includes the face. Although it is well recognized that facial dysmorphology is an important component of VCFS/DGS phenotype no good quantitative criteria for describing the facial dysmorphology are available. We propose to use an emerging method of three-dimensional photogrammetry to collect information about the facial features of patients clinically diagnosed to have VCFS/DGS. This method is rapid, analogous to taking a photograph, and provides a digitized three-dimensional image of the face of an individual. Software programs written by our colleagues and applied by us allow a large number of measurements that are accurate and reproducible. During the three-year period, we will enroll 300 patients in the study and obtain photogrammetric measurements as well as other clinical parameters from these patients. We hypothesize that facial features can be used as accurate diagnostic measures of these syndromes and that they would correlate with the deletion status and the size of the Ideletion. We have assembled a group of clinical and basic scientists as well a bioinformatician to address this problem.