RETT SYNDROME--PROGRAM PROJECT

这是一个多学科的研究计划， 临床的，交流的，神经物理学的，神经化学的， 流行病学、分子遗传学和神经病理学方面 Rett综合征 将采用多种分析模式 解决造成这种情况的根本机制 影响幼儿期女性的疾病。 临床 评估将利用系统的神经，发育， 运动行为分析，以验证现有的分期系统 对于Rett综合征，为临床诊断提供精确度， 为评估潜在治疗提供依据 战略布局 临床实验室检查将侧重于 先前描述的脑脊液异常（生物源性 胺代谢物、生物蝶呤和β-内啡肽）。 药理学 将通过系统评估对干预措施进行评估 记录并与合适的对照进行比较。 地位 Rett综合征的沟通技巧将由 言语和语言的行为评估， 听觉系统的电生理学评估。 这些 模式是研究的额外客观措施 治疗策略。 特征改变 呼吸模式和脑电图 通过复杂的视频脑电图方法进行检查。 本研究 在可能的情况下，还将评估上气道肌肉 类似于锥体外系疾病的功能障碍， 注意到;对Rett中观察到的癫痫发作类型进行严格分析 综合征;并在以下之前评估EEG 神经药理学治疗。 流行病学研究是 旨在检查Rett综合征的发生率， 确定的地理位置，并寻找产前和围产期 危险因素采用病例对照方法。 分子遗传学 研究将包括X-失活的模式和搜索 用高度多态性的探针进行亚显微的缺失。 一个 这项研究的一个重要组成部分是对家族病例的评估 使用X特异性的高度多态性探针以及具有 Rett表型。 Rett综合征的病理学研究将 检查尸检中的可用组织以及分析 肌肉和周围神经使用定量方法。 这项研究计划是由以下方面的共同努力发展而来的： 临床和基础研究人员，代表了一个重要的 扩大这些合作的机会。

This is a multidisciplinary research program for the study of the clinical, communicative, neurophysicological, neurochemical, epidemiologic, molecular genetic, and neuropathological aspects of Rett syndrome. Diverse analytic modalities will be employed to address the fundamental mechanism(s) responsible for this disorder affecting females in early childhood. The clinical assessment will utilize systematic neurologic, developmental, and motor-behavioral analyses to validate the existing staging system for Rett syndrome, to lend precision to the clinical diagnosis, and to provide a basis for the evaluation of potential treatment strategies. Clinical laboratory investigations will focus on previously-described abnormalities in cerebrospinal fluid (biogenic amine metabolites, biopterin, and B-endorphins). Pharmacologic intervention will be evaluated by the systematic assessments noted and compared with suitable controls. The status of communication skills in Rett syndrome will be examined by behavioral assessment of speech and language and by quantitative electrophysiologic evaluation of the auditory system. These modalities represent additional objective measures for the study of treatment strategies. Characteristics alterations in respiratory pattern and the electroencephalogram will be examined by sophisticiated video EEG methodologies. This study will also evaluate upper airway muscles where possible dysfunction similar to that in extra-pyramidal disorders has been noted; provide rigorous analysis of the seizure types seen in Rett syndrome; and assess the EEG prior to the following neuropharmacological treatment. Epidemiologic studies are designed to examine the occurrence of Rett syndrome in a defined-geographic locale and to search for prenatal and perinatal risk factors using case-control methodology. Molecular genetics studies will include the pattern of X-inactivation and the search for submicroscopic deletions using highly polymorphic probes. An important element of this study is evaluation of familial cases using X-specific, highly polymorphic probes as well as males with the Rett phenotype. Studies of pathology in Rett syndrome will examine available tissue from necropsy as well as analysis of muscle and peripheral nerves using quantitative methodologies. This research program has evolved from the concerted efforts of clinical and basic researcher and represents an important opportunity to extend these collaborations.