Population Health in Pediatric Sex Chromosome Aneuploidies

项目摘要/摘要 每400名婴儿中就有一名具有非典型数量的X和Y染色体，统称为性染色体 非整倍体(SCA)。尽管受管制计划协议影响的人数众多，但他们经常得不到承认，而且 研究严重不足，尤其是在儿童方面。随着无创产前检测的最新变化 建议，越来越多的婴儿被诊断出患有SCA。然而，我们能够提供准确的 对父母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 在全美主要的儿童医疗保健系统(PEDSnet)的基础上，向4,000名拥有SCA的青少年提供学习服务。在目标1中 我们将量化同时存在的心理和身体健康诊断和医疗保健利用情况， Turner，Klinefelter(XXY)，X三体和XYY综合征与普通儿科人群进行比较。在AIM 2我们将描述美国目前有这些疾病的儿童正在接受的临床护理实践。 最后，在目标3中，我们将为将来雌激素对特纳综合征女孩的比较有效性研究做准备。 通过开发和验证使用多个数据元素的算法来建立准确的 可计算的表型。通过这种新颖的、以人口为基础的方法来研究患有SCA的青年，我们将拥有 对患者和家属的遗传咨询产生直接影响，支持和促进 临床实践指南，并为未来针对婴儿、儿童和青少年的高影响研究做准备 在这些条件下。除了SCA研究的进展外，数据来源和方法学 该项目可能可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.