Population Health in Pediatric Sex Chromosome Aneuploidies

项目概要/摘要 每 400 名婴儿中就有 1 人的 X 和 Y 染色体数量不典型，统称为性染色体 非整倍体（SCAs）。尽管受 SCA 影响的人数很多，但他们常常未被识别，并且 尚未得到充分研究，特别是在儿童中。随着无创产前检测的最新变化 根据建议，更多患有 SCA 的婴儿正在被诊断出来。然而，我们有能力提供准确的 向家长提供的咨询或临床实践指南是有限的。该项目利用来自大型网络的数据 美国主要儿童医疗保健系统 (PEDSnet) 对超过 4,000 名患有 SCA 的青少年进行了研究。目标 1 我们将量化青少年共存的心理和身体健康诊断以及医疗保健利用 Turner、Klinefelter (XXY)、X 三体综合征和 XYY 综合征与一般儿科人群的比较。瞄准 2 我们将描述患有这些疾病的儿童在美国接受的当前临床护理实践。 最后，在目标 3 中，我们将为未来的特纳女孩雌二醇有效性比较研究做准备 通过开发和验证使用多个数据元素的算法来建立准确的综合症 可计算的表型。通过这种新颖的、基于人口的方法来研究青少年的 SCA，我们将 对患者和家庭的遗传咨询产生直接影响，支持并为遗传咨询的发展提供信息 临床实践指南，并为未来针对婴儿、儿童和青少年的高影响力研究做好准备 具备这些条件。除了 SCA 研究的进展之外，该研究的数据源和方法论 该项目可能会转化为其他遗传综合征和儿科罕见疾病。

PROJECT SUMMARY / ABSTRACT One in 400 infants have an atypical number of X and Y chromosomes, collectively known as sex chromosome aneuploidies (SCAs). Despite the number of individuals affected by SCAs, they often go unrecognized and are vastly understudied, particularly in children. With recent changes in non-invasive prenatal testing recommendations, more infants with SCAs are being diagnosed. However, our ability to provide accurate counseling to parents or guidelines for clinical practice is limited. This project utilizes data from a large network of major children’s healthcare systems across the US (PEDSnet) to study >4,000 youth with SCAs. In Aim 1 we will quantify co-existing mental and physical health diagnoses and healthcare utilization in youth with Turner, Klinefelter (XXY), Trisomy X, and XYY syndromes compared to the general pediatric population. In Aim 2 we will describe current clinical care practices that children with these conditions are receiving in the US. Finally, in Aim 3 we will prepare for a future comparative effectiveness study of estradiol in girls with Turner syndrome by developing and validating an algorithm using multiple data elements to establish an accurate computable phenotype. Through this novel, population-based approach to study youth with SCAs, we will have an immediate impact on genetic counseling for patients and families, support and inform the development of clinical practice guidelines, and prepare for future high-impact studies for infants, children, and adolescents with these conditions. In addition to advances for SCA research, the data source and methodologies from this project may be translatable to other genetic syndromes and pediatric rare diseases.