Primary Ciliary Dyskinesia: A Clinical Review

Abstract

Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous, motile ciliopathy, characterized by neonatal respiratory distress, recurrent upper and lower respiratory tract infections, subfertility, and laterality defects. Diagnosis relies on a combination of tests for confirmation, including nasal nitric oxide (nNO) measurements, high-speed videomicroscopy analysis (HSVMA), immunofluorescent staining, axonemal ultrastructure analysis via transmission electron microscopy (TEM), and genetic testing. Notably, there is no single gold standard confirmatory or exclusionary test. Currently, 54 causative genes involved in cilia assembly, structure, and function have been linked to PCD; this rare disease has a spectrum of clinical manifestations and emerging genotype-phenotype relationships. In this review, we provide an overview of the structure and function of motile cilia, the emerging genetics and pathophysiology of this rare disease, as well as clinical features associated with motile ciliopathies, novel diagnostic tools, and updates on genotype-phenotype relationships in PCD.

Keywords: bronchiectasis; cilia; genotype; motile ciliopathy; phenotype; primary ciliary dyskinesia.

Figure 1

The location and function of the 54 known genes implicated in PCD. (A). Respiratory Epithelial Cell. * DNAH9 and DNAH11 are represented twice in this figure, including in panel C, however, these genes are important in ODA structure in different location s along the axoneme length, as demonstrated here. DA = dynein arm. (B). Cilium. IFT = intraflagellar transport. (C). Axoneme (in cross-section). The outer doublet A and B microtubules are labeled. The cross-section of the axoneme shows the “9 + 2” structure of microtubules in the motile cilium. ODA = outer dynein arm; IDA = inner dynein arm. Illustration by ©Jessica Holland 2024.