A Prospective Natural History Study of Angelman Syndrome: A Fresh Approach to a 10-year Longitudinal Study to Facilitate Development of Novel Therapeutic Products

项目摘要 安杰曼综合征(AS)是一种神经发育障碍，以智力残疾、癫痫发作、 行为失常，很少说话或不说话。稳健的纵向、前瞻性收集的自然历史数据 临床试验设计的基础，包括选择适当的结果衡量标准。这是因为 自然历史研究试图通过引入新的成果措施来解决下面列出的未得到满足的需求， 包括积极开发AS治疗方法的制药公司建议的： (I)目前的成果衡量标准没有充分评估患有自闭症的个人的沟通技能，包括 增强和替代通信(AAC)设备的使用。 (Ii)焦虑是一些自闭症患者的一种衰弱症状，尚未得到系统检查。 (Iii)强直性脊柱炎患者所面对的运动和语言障碍对他们在 最广泛使用的评估工具(贝利婴儿发展量表，BSID)和结果 低估了他们的能力。 (4)对治疗效果的评价受到有效结果衡量标准数量不足的限制。 (V)由于成人参与者人数较少，人们对成人AS的自然历史了解甚少。 总体目标是增加对AS长期自然历史的了解，并获得AS的特异性 可以在临床试验中使用的结果衡量标准，以最终改善他们的护理。具体的 目标是： 目的1：在儿童和成人中进行一项前瞻性、纵向的AS自然历史研究，使用 研究人员观察和父母报告的结果衡量标准，这将对未来的临床试验有用。 目标2：通过减少运动和语言带来的偏见，使BSID适应AS人群 损害，并试行其使用。 探索性目标：评估使用照顾者获得的视频记录在参与者的 自然环境，以研究个人使用AAC设备的能力。 参与者将参加年度评估(在3个实际地点并通过远程参与)，包括 病史/发育史，体检(现场参与者)，以及一系列发育和 行为测量。对于实际站点的参与者，修改后的BSID版本删除了 精细运动障碍和完成速度导致的认知领域的惩罚，以及 学分将在表现力语言领域的非语言交流方式，将得到执行。视频 参与者的录音将由使用AAC设备的专家进行编辑和评分。

Project Summary Angelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, seizures, disturbed behavior and little/no speech. Robust longitudinal, prospectively collected, natural history data are the bedrock for the design of clinical trials, including selection of appropriate outcome measures. This AS Natural History Study seeks to address the unmet needs listed below by introducing new outcome measures, including those suggested by pharmaceutical company actively developing treatments for AS: (i) Current outcome measures do not adequately assess communication skills of individuals with AS, including the use of augmentative and alternative communication (AAC) devices. (ii) Anxiety, a debilitating symptom in some individuals with AS, has not been examined systematically. (iii) The motor and language impairments faced by individuals with AS negatively impacts their scores on the most widely-used assessment tool (Bayley Scales of Infant Development, BSID) and results in an underestimation of their abilities. (iv) Evaluation of treatment effects is limited by an inadequate number of validated outcome measures. (v) The natural history of AS in adults is poorly understood due to small number of adult participants. The overall goal is to increase understanding of the long-term natural history of AS and obtain AS-specific norms for outcome measures that can be used in clinical trials, to ultimately improving their care. The specific aims are: Aim 1: To conduct a prospective, longitudinal natural history study of AS in both children and adults, using investigator-observed and parent-reported outcome measures that will be useful for future clinical trials. Aim 2: Adapt the BSID for the AS population, by lessening the bias introduced by motor and language impairments, and pilot its use. Exploratory Aim: To assess the feasibility of using video recordings obtained by caregivers in the participant's natural environment to study the abilities of individuals with AS to use AAC devices. Participants will be enrolled (at 3 physical sites and via remote participation) for annual assessments including medical/developmental history, physical examination (on-site participants), and a battery of developmental and behavioral measures. For participants at the physical sites, a modified version of the BSID, which removes the penalty in the cognitive domain introduced by fine motor impairments and speed of accomplishment, and credits non-verbal communication modalities in the expressive language domain, will be administered. Video recordings of participants will be edited and scored by an expert in the use of AAC devices.