Using Longitudinal Data to Characterize the Natural History of Fragile X Syndrome--Component A

 描述（由申请人提供）：脆性X综合征（FXS）是智力残疾和自闭症谱系障碍的最常见遗传原因，估计男性频率约为1：4000-5000，女性约为1：8000。它影响到全世界所有种族和族裔群体。尽管多年的工作，我们对FXS的自然历史以及FXS个人和家庭的需求的了解仍然存在相当大的差距。对共发疾病的研究通常通过使用横截面数据单独关注每种疾病，而不检查与FXS其他特征的关联，也不采取系统方法。此外，为了进行设计良好的临床试验，捕获整个疾病谱，需要确定FXS患者的自然史。对于患有FXS的成年人来说尤其如此，对于他们的生活轨迹和医疗并发症几乎一无所知。 2012年实施了脆性X染色体在线登记研究数据库（FORWARD），以填补公认的知识空白。FORWARD由患者和家庭登记处以及由来自FXS患者的临床医生和父母报告的数据填充的纵向数据库组成。作为脆性X临床和研究联盟成员的脆性X诊所与国家脆性X基金会和疾病控制和预防中心合作，向FORWARD提供了临床医生和家长报告的数据。目前，该数据库包括超过850名FXS参与者，具有基线数据收集点。纵向部分现在包括250多名有随访数据的受试者。 本提案的目标是通过以下方式扩大“前进”：1）增加基线和纵向数据点的数量，2）构建新的数据收集工具以招募和表征患有FXS的成年人，以及3）扩大努力以增加目前在FXS研究中代表性不足的参与者的数量。在FORWARD中描述的纵向队列将允许脆弱X临床研究和公共卫生社区检查治疗和服务使用、教育环境、医疗问题以及从父母和临床医生报告的组合中获得的其他特征。据我们所知，FORWARD现在是关于FXS患者参加专业诊所的最大数据收集，具有临床医生报告信息收集的附加价值。本申请中提出的扩展，结合在组合组件C站点收集的详细的纵向认知，适应性，语言，运动，行为，社会和生活质量数据，对于进一步了解FXS的自然史以及FXS个体和家庭在其生命周期中的需求至关重要。

 DESCRIPTION (provided by applicant): Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism spectrum disorder, with an estimated frequency of about 1:4000-5000 in males and about 1:8000 in females. It affects all racial and ethnic groups worldwide. Despite the years of work, there are still considerable gaps in our knowledge about the natural history of FXS and the needs of individuals and families with FXS. Studies of co-occurring conditions have typically focused on each condition alone by using cross-sectional data, without examining the associations with other features of FXS or without taking a systems approach. Furthermore, in order to conduct well-designed clinical trials that capture the entire spectrum of the disorder, the natural history of those with FXS needs to be determined. This is particularly true for adults with FXS, about whom almost nothing is known regarding life trajectory and medical complications. The Fragile X Online Registry With Accessible Research Database (FORWARD) was implemented in 2012 to fill the recognized gap in knowledge. FORWARD consists of a patient and family registry and a longitudinal database populated by clinician- and parent-reported data from individuals living with FXS. Fragile X clinics that are members of the Fragile X Clinical and Research Consortium, in partnership with the National Fragile X Foundation and the Centers for Disease Control and Prevention, have contributed clinician- and parent- reported data to FORWARD. Currently, the database includes over 850 participants with FXS with a baseline data collection point. The longitudinal component now includes over 250 subjects with follow-up data. The goals of this proposal are to expand FORWARD by: 1) increasing the number of baseline and longitudinal data points, 2) building new data collection tools to enroll and characterize adults with FXS, and 3) expanding efforts to increase the number of participants who are currently under-represented in FXS studies Through analyses coordinated with Component B, the resulting longitudinal cohort characterized in FORWARD will allow the fragile X clinical research and public health community to examine changes over time in use of treatments and services, educational setting, medical problems, and other characteristics obtained from a combination of parent and clinician report. To our knowledge, FORWARD is now the largest collection of data about individuals with FXS attending specialty clinics, with the added value of the collection of clinician- reported information. The expansion proposed in this application, in combination with the detailed longitudinal cognitive, adaptive, language, motor, behavioral, social, and quality of life data to be collected at the combined Component C sites, is essential to further our understanding of the natural history of FXS and the needs of individuals and families with FXS across their life spans.