Developmental Trajectories in ARID1B-Related Disorder – a Multi-Method Multi-Site Prospective Natural History Study

ARID 1B是非遗传性神经发育障碍（NDD）中最常见的突变单基因，其患病率约为9，500人中的1人。ARID 1B相关障碍（ARID 1B-RD）在幼儿期表现为中度至重度发育迟缓，患有该障碍的儿童和成人具有智力残疾（ID），并且通常被诊断为自闭症谱系障碍沿着许多其他临床体征。尽管ARID 1B-RD的高患病率和广泛的衰弱效应，目前对这种疾病如何随着时间的推移而发展的理解是非常有限的。拟议项目将通过采用前瞻性纵向多方法设计来解决这一差距。具体而言，我们将在六个研究中心监测100名患有ARID 1B-RD的2-18岁儿童和青少年的发育，为期三年。监测将涉及（a）管理标准化NDD评估，并辅以ARID 1B-RD特定工具;（B）评估ARID 1B-RD的生物学方面（例如，脑电活动）;（c）通过护理人员报告收集日常生活数据，以及使用智能手表和麦克风收集音频和运动数据。该项目团队带来了一套多样化的互补技能，并与领先的患者倡导组织合作。该项目将全面了解ARID 1B-RD的进展情况。这些数据将有助于确定和验证可衡量的干预目标，从而促进为全世界数千名儿童制定有效的治疗方法。

ARID1B is the most frequently mutated single gene among neurodevelopmental disorders (NDDs) that are not inherited, with an approximated prevalence of one in 9,500 individuals. ARID1B-related disorder (ARID1B-RD) manifests in early childhood as moderate to severe developmental delay, and children and adults with the disorder have intellectual disability (ID) and are often diagnosed with autism spectrum disorder along with many other clinical signs. Despite ARID1B-RD’s high prevalence and extensive debilitating effects, the current understanding of how the disorder develops over time is strikingly limited. The proposed project will address this gap by employing a prospective longitudinal multi-method design. Specifically, in six sites, we will monitor the development of 100 children and adolescents aged 2-18 with ARID1B-RD for three years. Monitoring will involve (a) administration of standardized NDD assessments complemented by ARID1B-RD-specific tools; (b) evaluation of biological aspects of ARID1B-RD (for example, electric brain activity); and (c) collection of daily life data via caregivers’ reports, and audio and movement data using smartwatches and microphones. The project team brings a diverse set of complementary skills and collaborates with a leading patient advocacy organization. The project will generate a comprehensive picture of the progression of ARID1B-RD . The data will allow identifying and validating measurable targets for interventions, thus facilitating the development of effective treatments for thousands of children worldwide.