Population Health in Pediatric Sex Chromosome Aneuploidies

项目概要/摘要 每400个婴儿中就有一个有非典型数量的X和Y染色体，统称为性染色体 非整倍体（SCA）。尽管受《管制协议》影响的人很多，但他们往往得不到承认， 尤其是在儿童身上随着最近非侵入性产前检测的变化 根据建议，更多患有SCA的婴儿正在被诊断出来。然而，我们提供准确 对父母的咨询或临床实践的指导是有限的。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）研究了超过4,000名患有SCA的青少年。目标1 我们将量化青少年同时存在的心理和身体健康诊断以及医疗保健利用率， Turner、Klinefelter（XXY）、X三体和XYY综合征与一般儿科人群的比较。在Aim中 2我们将描述目前的临床护理实践，这些条件的儿童正在接受在美国。 最后，在目标3中，我们将为将来在Turner女孩中进行雌二醇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 可计算表型透过这个以人口为本的崭新研究方法，我们可以 对患者和家庭的遗传咨询产生直接影响，支持和告知 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 在这些条件下。除了SCA研究的进展之外， 该项目可能适用于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.