Primary Ciliary Dyskinesia and Overlapping Syndromes

描述（由申请人提供）： 原发性纤毛运动障碍（PCD）是一种常染色体隐性遗传疾病，可导致粘膜纤毛清除功能受损，其特征为复发性支气管炎、鼻窦炎、中耳炎和支气管扩张。在这种疾病中，运动纤毛，其中包括一个配置的9个外部微管对和一个中央对，表现出有缺陷的动力蛋白武器在大多数患者中，和其他表现出有缺陷的轴丝组件或具有正常的纤毛超微结构。在过去的10年中，在理解潜在缺陷，识别导致PCD的特定基因突变以及定义患有该疾病的患者的自然临床过程方面取得了很大进展。到目前为止，三个基因（DNAI 1，DNAH 11和DNAH 5）与“严重”（功能丧失）突变是30%的PCD患者的致病原因。尽管有这些最新的发展，诊断仍然很困难，这种疾病往往得不到承认。与其他（“原发性”/“感觉性”）非运动综合征重叠的运动性纤毛病变的谱也正在被确定，并且这些病症对临床表现的影响知之甚少。几乎没有证据可以描述最佳治疗实践。本次会议的目的是为国际专家提供一个机会，以建立一个工作组，以实现以下四个目标：（1）通过标准化诊断测试优化PCD的诊断;（2）通过全球网络定义PCD基因和基因突变;（3）优化PCD患者的临床护理，并建立临床研究网络，通过临床试验测试治疗方法;（4）通过全球网络定义PCD基因和基因突变。（4）完善纤毛病变的命名法，更好地定义重叠特征。 公共卫生相关性： 原发性纤毛运动障碍是一种运动纤毛的遗传性疾病，可导致复发性支气管炎、慢性鼻窦炎和支气管扩张或不可逆的气道损伤。这些表现的发生是因为纤毛不能有效地将粘液移出气道。在过去的10年里，在理解这种疾病的潜在病理生理学以及临床过程的自然史方面取得了很大进展。还开发了有助于诊断该疾病的改进工具，并确定了重叠的综合征。鉴于这些发展，应建立一个正式的国际工作组，以改善合作，并为临床试验网络提供机会。初级睫状体运动障碍卓越中心可以建立，以促进这一进程。NIH主办的一次会议将启动这些重要举措。

DESCRIPTION (provided by applicant): Primary ciliary dyskinesia (PCD), an autosomal recessive disorder leading to impaired mucocociliary clearance, is characterized by recurrent bronchitis, rhinosinusitis, otitis media and development of bronchiectasis. In this disease, the motile cilia, which consists of a configuration of nine outer microtubule pairs and a central pair, exhibit defective dynein arms in most patients, and others exhibit defective axonemal components or have normal ciliary ultrastructure. Over the past 10 years, much progress has occurred in understanding the underlying defect, in identifying specific genetic mutations leading to PCD, and in defining the natural clinical course of patients afflicted with the disorder. To date, three genes (DNAI1, DNAH11, and DNAH5) with "severe" (loss-of-function) mutations are disease-causing in 30% of patients with PCD. Despite these recent developments, diagnosis remains difficult and the disease often goes unrecognized. The spectrum of motile ciliopathies overlapping with other ("primary"/"sensory") non-motile syndromes is also being identified, and the impact of these conditions on clinical manifestations is poorly understood. There is minimal to no evidence describing best treatment practices. The objectives of this conference will be to provide an opportunity for international experts to establish a working group to meet the following four objectives: (1) To optimize diagnosis of PCD through standardization of diagnostic testing; (2) To define PCD genes and gene mutations through global networking; (3) To optimize clinical care of PCD patients and develop clinical research networks to test therapies through clinical trials; and (4) To refine nomenclature for ciliopathies and better define overlapping features. PUBLIC HEALTH RELEVANCE: Primary ciliary dyskinesia, a genetic disorder of the motile cilia, leads to recurrent bronchitis, chronic rhinosinusitis and bronchiectasis or irreversible airway damage. These manifestations occur because the cilia are not effective at moving mucous out of the airways. Over the past 10 years, much progress has occurred in understanding the underlying pathophysiology of this disease as well as the natural history of the clinical course. Improved tools that help in diagnosing the disease have also been developed and overlapping syndromes have been identified. Given these developments, a formal international working group should be established to improve collaborations as well as provide an opportunity for a clinical trial network. Primary ciliary dyskinesia centers of excellence could be established to facilitate this process. A NIH-sponsored conference would launch these important initiatives.