Rett syndrome, MECP2 Duplications, and Rett-related Disorders Natural History

描述(由申请人提供) 对Rett综合征(RTT)和RTT相关疾病长期感兴趣的多机构研究人员的这一竞争性更新延续了罕见疾病临床研究网络中的罕见疾病临床研究中心(RDCRC)。这项RDCRC将专注于三种不同的疾病：RTT，MECP2复制障碍，RTT相关疾病，包括CDKL5，FOXG1，以及具有MECP2突变但缺乏RTT临床标准的个体。对于RTT来说，有意义的治疗的近期潜力是有形的；对其他疾病的治疗潜力是有希望的。提出了三个总体的具体目标。1)对每种疾病的核心临床特征进行纵向和神经行为评估：正在进行的RTT NHS为组织和推进纵向研究提供了关键数据。RTT在临床变异性方面仍然存在实质性的问题，而不是仅仅通过特定的突变来解释。为其他疾病获取类似的数据也同样重要。2)执行强大的生物标记物和临床结果测量，以确定导致每个疾病的疾病严重程度的生物因素：为有效和有区别的结果测量提供关键指导是任何临床试验的关键特征，需要对这些疾病进行特殊考虑。3)识别和描述RTT和RTT相关疾病的神经生理学和神经影像相关性：了解特定容量测量、化学成分和神经生理学测量(如EEG和诱发电位)的变化对于提高临床知识至关重要。区域发展合作中心将保持广泛的培训和试点项目方案，直接与各自的国家技术援助机构合作。RDCRC将与患者倡导团体合作，确保建立全面的合作伙伴关系，并将主要依靠数据管理和协调中心进行方案管理、数据存储、网站门户和生物统计支持。UAB CCTS(CTSA)将与RDCRC充分合作，制定试点项目并提供更多的生物统计支持。网站界面将与RDCRC、DMCC和患者倡导团体联系起来，以确保相关信息的最广泛覆盖

DESCRIPTION (provided by applicant) This competitive renewal from a multi-institutional group of investigators with longstanding interest in Rett syndrome (RTT) and RTT-related disorders continues a Rare Disease Clinical Research Center (RDCRC) within the Rare Diseases Clinical Research Network. This RDCRC will focus on three distinct disorders: RTT, MECP2 duplication disorder, and the RTT-related disorders including CDKL5, FOXG1, and individuals with MECP2 mutations but lacking clinical criteria for RTT. The near-term potential for meaningful therapies is tangible for RTT; the treatment potential for the other disorders is promising. Three overarching specific aims are proposed. 1) Perform longitudinal and neurobehavioral assessments on the core clinical features of each disorder: The on-going RTT NHS has provided critical data for organizing and advancing longitudinal studies. Substantial questions remain for RTT in terms of clinical variability not explainable solely by the specific mutations. Acquisition of similar data for the other disorders is equally important. 2) Perform robust biomarker and clinical outcome measures to identify biological factors that contribute to disease severity in each disorder: Providing critical guidance to effective and discriminant outcome measures is a crucial feature of any clinical trial and requires special consideration for these disorders. 3) Identify and characterize neurophysiological and neuroimaging correlates of disease severity in RTT and RTT-related disorders: Understanding alterations in specific volumetric measures, chemical composition, and neurophysiological measures such as EEG and Evoked Potentials are critical to advancing clinical knowledge. The RDCRC will maintain extensive training and pilot project programs cooperating directly with the respective CTSAs. The RDCRC will work with the Patient Advocacy Groups to ensure a full partnership and will rely principally on the Data Management and Coordinating Center for protocol management, data storage, a website portal, and biostatistical support. The UAB CCTS (CTSA) will fully cooperate with the RDCRC with pilot project development and additional biostatistical support. Website interfaces will be linked with the RDCRC, the DMCC, and the Patients Advocacy groups to ensure the widest reach of relevant information