Elucidating the causes and consequences of sleep disturbances in children with rare genetic syndromes

项目摘要 遗传决定的神经发育综合征儿童的医疗管理代表了一个 严重的公共卫生负担。虽然这些综合征个别罕见，但它们是共同的。 值得注意的是，睡眠障碍是这些患者中最常见的并发症。睡眠 数量和质量被证明对神经发育和新陈代谢是重要的。未经治疗的睡眠 干扰可能对神经功能、生活质量和生产力产生长期的负面影响。 虽然有许多因素导致神经发育综合征儿童的睡眠问题，但有效 这些问题的治疗降低了许多其他症状的严重程度。这表明睡眠是一种 可改变的风险因素，如果得到有效管理，可能会改善这些人的健康结果和生活质量 患者及其家属。了解睡眠问题的原因和后果对于 确定治疗睡眠障碍的有效方法。本研究旨在阐明 Prader-Willi综合征（PWS）儿童睡眠障碍的原因和后果， 遗传条件和早发性病态肥胖的已知原因。这将是第一个使用 来自电子健康记录（EHR）的数据，以评估收集的真实世界临床信息， 患有罕见遗传综合征的儿童我们将开发一种方法来整合多种类型的EHR衍生 数据1）定义在PWS儿童中观察到的睡眠问题类型，2）定义 睡眠呼吸障碍，症状严重程度和其他重要的合并症，如 PWS中的肥胖，以及3）确定PWS的分子遗传类别的差异是否与 睡眠障碍的表达差异。拟议的项目提供了前所未有的机会， 提高我们对睡眠、神经发育、肥胖和遗传之间关系的理解， 孩子从睡眠研究报告和遗传信息中提取客观睡眠指标的方法 基因检测结果将为确定新的治疗方法提供途径。 罕见遗传缺陷儿童的睡眠障碍

PROJECT SUMMARY Medical management of children with genetically determined neurodevelopmental syndromes represents a significant public health burden. While these syndromes are individually rare, they are collectively common. Notably, sleep disturbances are some of the most prevalent co-occurring conditions in these patients. Sleep quantity and quality is evidenced to be important to neurodevelopment and metabolism. Untreated sleep disturbances may have long-term negative impacts on neurological function, quality of life and productivity. While many factors contribute to sleep problems in children with neurodevelopmental syndromes, effective treatment of these issues reduces severity of numerous other symptoms. This suggests that sleep is a modifiable risk factor that, when effectively managed, may improve health outcomes and quality of life for these patients and their families. Understanding the causes and consequences of sleep problems is crucial to identifying effective approaches to treatment of sleep disturbances. This study proposes to focus on elucidating the causes and consequences of sleep disturbances in children with Prader-Willi syndrome (PWS), a classical genetic condition and known cause of early-onset morbid obesity. This will be one of the first studies to use data derived from electronic health records (EHRs) to evaluate real-world clinical information collected in children with rare genetic syndromes. We will develop an approach to integrate multiple types of EHR-derived data to 1) define the types of sleep problems observed in children with PWS, 2) define the relationship between sleep disordered breathing, symptom severity and expression of other important comorbidities—like obesity—in PWS, and 3) determine if differences in the molecular genetic classes of PWS are associated with differences in expression of sleep disturbances. The proposed project offers unprecedented opportunity to improve our understanding of the relationship between sleep, neurodevelopment, obesity, and genetics in children. An approach for extracting objective sleep measures from sleep study reports and genetic information from genetic testing results will be established providing an avenue for identification of novel treatments of sleep disturbances in children with rare genetic defects.