Bhatt Reena, Hogg Claire
Royal Brompton Hospital, London, UK.
Paediatric Respiratory Medicine, Imperial College London, London, UK.
Breathe (Sheff). 2020 Jun;16(2):200047. doi: 10.1183/20734735.0047-2020.
Primary ciliary dyskinesia (PCD) is an inherited disorder of clinical and genetic heterogeneity resulting from mutations in genes involved in the transport, assembly and function of motile cilia. The resulting impairment in mucociliary clearance means patients suffer from chronic progressive lung disease, bronchiectasis, rhinosinusitis and middle ear disease. Subfertility is common to both male and female patients. Situs abnormalities occur in around half of patients, with a subgroup suffering more complex situs arrangements where congenital heart defects or other organ abnormalities frequently coexist. Variations from the classical PCD phenotype are increasingly recognised where overlapping features across a range of motile and nonmotile ciliopathies are redefining our approach to both diagnosis and management of these complex conditions. PCD offers an ideal opportunity for direct visualisation of ciliary function and structure, following nasal brush biopsy, allowing opportunities for researchers to directly interrogate the downstream impact of loss of function mutations. In turn, this has led to rapid advances in the development of new diagnostic tests. These advances mean that PCD is an excellent disease model for understanding the genetic and mechanistic causes of the clinical phenotype for all respiratory ciliopathies. Furthermore, the overlapping role of motile ciliary defects in a wider set of complex and syndromic disorders related to loss of function mutations in primary, nonmotile cilia has been recognised. As we better understand the role of ciliary defects in a broad spectrum of diseases, we should aim to map out a framework through which we can identify, diagnose and treat all respiratory ciliopathies.
Primary ciliary dyskinesia is just one of a group of conditions where a heterogeneous array of genetic mutations affect the assembly or structure of motile cilia.Overlapping phenotypes between motile and nonmotile ciliopathies are redefining the diagnostic and therapeutic approach to encompass all ciliopathy patients with a respiratory phenotype.An extended diagnostic algorithm may be required to capture the majority of cases with a respiratory ciliopathy, including patients with syndromic ciliopathies.The terminology around disorders of motile cilia is becoming more descriptive to better reflect the heterogeneity and underlying disease mechanisms across the spectrum of respiratory ciliopathies.
To summarise the existing knowledge base around the disease mechanisms for respiratory ciliopathies, including primary ciliary dyskinesia (PCD).To explore and understand the reasons for changing terminology around respiratory ciliopathies.To emphasise key messages around the diagnosis and treatment of all ciliopathies.Diagnosing PCD is complex and time consuming, and there is no single stand-alone test that can confirm or exclude a diagnosis in all cases.
原发性纤毛运动障碍（PCD）是一种具有临床和遗传异质性的遗传性疾病，由参与运动性纤毛运输、组装和功能的基因突变引起。由此导致的黏液纤毛清除功能受损意味着患者会患上慢性进行性肺病、支气管扩张、鼻窦炎和中耳疾病。男性和女性患者都常有生育力低下的问题。约半数患者会出现内脏反位异常，其中一小部分患者的内脏反位情况更为复杂，常伴有先天性心脏缺陷或其他器官异常。经典PCD表型的变异越来越受到认可，一系列运动性和非运动性纤毛病的重叠特征正在重新定义我们对这些复杂病症的诊断和管理方法。通过鼻刷活检，PCD为直接观察纤毛功能和结构提供了理想机会，使研究人员有机会直接探究功能丧失突变的下游影响。反过来，这也推动了新诊断测试的快速发展。这些进展意味着PCD是理解所有呼吸道纤毛病临床表型的遗传和机制原因的优秀疾病模型。此外，人们已经认识到运动性纤毛缺陷在与原发性非运动性纤毛功能丧失突变相关的更广泛的复杂和综合征性疾病中也发挥着重叠作用。随着我们更好地理解纤毛缺陷在广泛疾病中的作用，我们应致力于规划一个框架，以便能够识别、诊断和治疗所有呼吸道纤毛病。
原发性纤毛运动障碍只是一组疾病中的一种，在这些疾病中，一系列异质性基因突变会影响运动性纤毛的组装或结构。运动性和非运动性纤毛病之间的重叠表型正在重新定义诊断和治疗方法，以涵盖所有具有呼吸道表型的纤毛病患者。可能需要扩展诊断算法来确诊大多数呼吸道纤毛病病例，包括患有综合征性纤毛病的患者。关于运动性纤毛疾病的术语正变得更具描述性，以更好地反映呼吸道纤毛病谱系中的异质性和潜在疾病机制。
总结关于呼吸道纤毛病（包括原发性纤毛运动障碍（PCD））疾病机制的现有知识库。探索并理解呼吸道纤毛病术语变化的原因。强调关于所有纤毛病诊断和治疗的关键信息。诊断PCD复杂且耗时，没有单一的独立测试能在所有情况下确诊或排除诊断。
