Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is caused by ultrastructural ciliary defects that lead to abnormal ciliary beating and, subsequently, mucociliary dysfunction. PCD presents clinically with bronchiectasis, sinusitis, and, in up to 50% of cases, situs inversus. The ultrastructural defects of cilia are diverse but include in many cases outer and/or inner dynein arms. Recent advances have shown that ciliary defects in the embryonic node during development are responsible for the random right–left axis determination in these patients. Genetic approaches have elucidated at least some of the heterogeneous molecular defects underlying PCD. This article summarizes the current knowledge about this disease with respect to clinical manifestations, laboratory diagnosis and pathogenesis, situs inversus, genetics, and therapeutic considerations. A report of a patient with the seemingly disparate symptoms of bronchiectasis and situs inversus 100 years ago is likely the first account of primary ciliary dyskinesia (PCD). Kartagener refined the description of the syndrome to include chronic sinusitis. However, only approximately 30 years ago, Afzelius and co-workers identified absent axonemal dynein arms in motile cilia with the ‘9þ 2’ microtubular arrangement of the airway epithelium and in sperm flagella as the cellular defect leading to what had come to be known as Kartagener’s syndrome or immotile cilia syndrome. Recent studies have demonstrated considerable heterogeneity of dynein arm morphology at the ultrastructural level among patients with this syndrome. Moreover, half of patients with clinical symptoms and ciliary ultrastructural defects do not exhibit situs inversus. Thus, the term PCD is currently used to describe individuals with congenital abnormalities of cilia and flagella and the clinical symptoms of bronchiectasis and chronic sinusitis. Kartagener’s syndrome, which in addition to bronchiectasis and sinusitis includes situs inversus, is thus considered a subset of PCD. The overall incidence of PCD is 1 in 20 000, with enrichment in certain populations. PCD is usually an autosomal recessive disorder, but unusual cases of PCD with apparent dominant or X-linked inheritance pattern have also been reported. Clinical Manifestations Many clinical features of PCD reflect abnormal ciliary beating leading to impaired mucociliary clearance. Symptoms of mucociliary dysfunction in the nose, sinuses, and middle ear are recurrent or persistent rhinitis, sinusitis, and otitis media. Chronic productive cough is the major symptom of mucociliary dysfunction in the lower airways, and this chronic bronchitis can lead to bronchiectasis. Neonatal respiratory problems, situs inversus, and male infertility, common in PCD, are most likely linked to ciliary or flagellar dysfunction. Chronic nasal congestion is common and often present from early infancy, with little or no seasonal variation. Almost all PCD patients have chronic sinusitis, radiographically demonstrated by mucosal thickening, cloudiness, and/or opacification of all paranasal sinuses. Nasal polyps occur in approximately one-third of patients and may be apparent in early childhood. Almost all patients have chronic otitis media that is much more prominent in early childhood. At the time of diagnosis, most patients PRIMARY CILIARY DYSKINESIA 485