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

项目总结 对患有遗传神经发育综合征的儿童的医疗管理代表着一种 严重的公共卫生负担。虽然这些症状是个别罕见的，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共生疾病之一。沉睡 数量和质量被证明对神经发育和新陈代谢很重要。未经治疗的睡眠 精神障碍可能会对神经功能、生活质量和生产力产生长期的负面影响。 虽然许多因素导致神经发育综合征儿童的睡眠问题，但有效 对这些问题的治疗可以减轻许多其他症状的严重性。这表明睡眠是一种 可修改的风险因素，如果有效管理，可能会改善这些人的健康结果和生活质量 病人和他们的家人。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。这项研究建议集中于澄清 普拉德-威利综合征(PWS)儿童睡眠障碍的原因和后果 早发性病态肥胖的遗传状况和已知原因。这将是最早使用的研究之一 来自电子健康记录(EHR)的数据，用于评估收集的真实临床信息 患有罕见遗传综合征的儿童。我们将开发一种方法来集成多种类型的EHR派生的 数据用于1)定义在PWS儿童中观察到的睡眠问题的类型，2)定义关系 睡眠呼吸障碍、症状严重程度和其他重要的合并症的表现 肥胖--在PWS中，以及3)确定PWS分子遗传类别的差异是否与 睡眠障碍的表现差异。拟议中的项目提供了前所未有的机会 提高我们对睡眠、神经发育、肥胖和遗传学之间的关系的理解 孩子们。一种从睡眠研究报告和遗传信息中提取客观睡眠指标的方法 从基因检测结果将建立一条途径，以确定新的治疗方法 罕见基因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.