Adults with Fragile X Syndrome: Health and Life Course Trajectories

这是一个连续申请，用于额外5年的支持，以进行比较和前瞻性研究， 脆性X综合征（FXS）是一种遗传性神经发育障碍，由脆性X染色体的三核苷酸扩增引起。 X染色体上FMR 1基因中的CGG重复序列。FXS显著改善健康和功能 开始于幼儿期并持续一生的损伤。它是智力障碍最常见的遗传原因。 残疾和孤独症，造成沉重的家庭负担和公共卫生影响。关键是，绝大多数 关于FXS临床表型的知识来自于对儿童的研究， 未知领域这项研究的目的是调查如何健康和行为 FXS患者的功能在整个成年期发生变化，并确定缓解或恶化健康的因素 和行为功能。这将是第一项有力解决这些问题的研究 超过成年早期。我们有三个具体目标。对于目标1，我们将确定健康状况的概况 以及FXS成人患者的医疗保健利用率。使用病例对照设计，我们建议检查健康 新确定的368名成年人（年龄18至80岁以上）的队列中，他们的电子健康中有FXS代码 记录（EHR）- 162名女性，206名男性，77名非白色，291名白色。这些成年人将从11个健康 包括芝加哥地区以患者为中心的结果研究网络（CAPriCORN）的护理系统。使用 EHR，我们将研究FXS成人与年龄和性别匹配的对照组之间的差异， 在健康和医疗保健利用方面有FXS。我们将探讨不同的子组之间的差异， 根据年龄（成年早期、中年、老年）以及性别和种族定义的FXS成人。为宗旨 2、采用18年的纵向设计，我们将定义健康的生命轨迹， 行为功能与FXS成人和调查年龄相关的风险。在5号楼的基础上- 收集重复测量，我们将前瞻性地收集另外3轮数据，从而产生多达8个 在18年的时间里重复测量（n=182对FXS成人及其前突变携带者 母亲）。到拟议的研究结束时，我们现有纵向样本中的成年人平均年龄将达到37岁 年龄，59%为35岁或以上（最大年龄为72岁）。我们将采用加速纵向 旨在阐明健康、执行功能、沟通、行为问题和日常生活变化的设计 成年后的技能。我们将测试风险增加的年龄以及性别和自闭症对这些的影响。 轨迹对于目标3，使用与目标2相同的样本，我们将研究成年人的生命历程轨迹 与FXS相关的家庭和社会背景的决定因素-家庭关系，居住状况 FXS的成年人，父母的教育水平，家庭收入，健康保险类型，服务， 邻里SES通过采用多种创新方法和不同的数据来源，拟议的研究将 扩展有关FXS的知识，超越成年早期，并阐明FXS在中年及以后的变化。

This is a continuation application for an additional 5 years of support for a comparative and prospective study of Fragile X Syndrome (FXS), an inherited neurodevelopmental disorder caused by a trinucleotide expansion of CGG repeats in the FMR1 gene on the X chromosome. FXS results in significant health and functional impairments that begin in early childhood and last a lifetime. It is the most common inherited cause of intellectual disability and autism, with substantial family burden and public health impacts. Critically, the great majority of knowledge about the FXS clinical phenotype derives from research on children, leaving adulthood a vast uncharted territory. The purpose of the proposed research is to investigate how the health and behavioral functioning of individuals with FXS change across adulthood and to identify factors that alleviate or worsen health and behavioral functioning during the adult years. It will be the first study to robustly address these questions beyond early adulthood. We address 3 Specific Aims. For Aim 1, we will determine profiles of health conditions and health care utilization for adults with FXS. Using a case-control design, we propose to examine the health of a newly ascertained cohort of 368 adults (age 18 to 80+) who have a code for FXS in their electronic health records (EHRs) – 162 women, 206 men, 77 nonwhite, and 291 white. These adults will be drawn from 11 health care systems comprising the Chicago Area Patient-Centered Outcomes Research Network (CAPriCORN). Using EHRs, we will examine differences between adults with FXS and age- and sex-matched controls who do not have FXS with respect to health and health care utilization. We will probe differences between sub-groups of adults with FXS defined by age (early adulthood, midlife, older adulthood) as well as by sex and race. For Aim 2, using a longitudinal design that will span 18 years, we will define life course trajectories in health and behavioral functioning among adults with FXS and investigate age-related risk. Building on the 5 already- collected repeated measures, we will prospectively gather 3 additional rounds of data, resulting in up to 8 repeated measures over the 18-year period (n=182 dyads of adults with FXS and their premutation carrier mothers). By the end of the proposed study, the adults in our existing longitudinal sample will average 37 years of age, with 59% being age 35 or older (the oldest will be age 72). We will employ an accelerated longitudinal design to elucidate changes in health, executive functioning, communication, behavior problems, and daily living skills across adulthood. We will test for ages of increased risk and the effects of sex and autism on these trajectories. For Aim 3, using the same sample as in Aim 2, we will examine how life course trajectories of adults with FXS are associated with familial and social contextual determinants – family relationships, residential status of the adult with FXS, educational level of parents, family income, type of health insurance, services, and neighborhood SES. By employing multiple innovative methods and varied data sources, the proposed study will extend knowledge about FXS beyond early adulthood and elucidate how FXS changes in midlife and beyond.