Diagnosis and management of primary ciliary dyskinesia

Abstract

Primary ciliary dyskinesia (PCD) is an inherited autosomal-recessive disorder of motile cilia characterised by chronic lung disease, rhinosinusitis, hearing impairment and subfertility. Nasal symptoms and respiratory distress usually start soon after birth, and by adulthood bronchiectasis is invariable. Organ laterality defects, usually situs inversus, occur in ∼50% of cases. The estimated prevalence of PCD is up to ∼1 per 10,000 births, but it is more common in populations where consanguinity is common. This review examines who to refer for diagnostic testing. It describes the limitations surrounding diagnosis using currently available techniques and considers whether recent advances to genotype patients with PCD will lead to genetic testing and screening to aid diagnosis in the near future. It discusses the challenges of monitoring and treating respiratory and ENT disease in children with PCD.

Keywords: Kartagener syndrome; ciliary motility disorders; diagnosis; primary ciliary dyskinesia; treatment.

Figure 1

Cartoon of a respiratory cilium in transverse section as seen by transmission electron microscopy (TEM). Respiratory cilia have a ‘9+2’ arrangement with a central pair of single microtubules running the length of the ciliary axoneme surrounded by nine peripheral microtubule doublets. Nexin and radial spokes maintain the organisation of the axonemal structure. Attached to the peripheral microtubules are inner and outer dynein arms that generate the force for ciliary beating. Abnormalities of the dynein arms affect ciliary beating. HYDIN projections on the central pair of microtubules are not usually seen by routine TEM (Cartoon image provided by Robert L Scott).

Figure 2

Transmission EM of a respiratory cilia from (A) a healthy individual. Representative nasal epithelium cilia from patients with primary ciliary dyskinesia (PCD) caused by (B) outer and inner dynein arm defects (C) transposition defect: some cilia demonstrate absence of a central microtubule pair (‘9+0’); in other cilia a peripheral microtubule doublet has crossed to take the central position providing an apparent ‘8+2’ structure (D) microtubular disorganisation. EM images obtained using FEI Tecnai 12 transmission electron microscope (FEI UK Limited, Cambridge, UK) at 80 kV). EM images provided by P Goggin (Primary Ciliary Dyskinesia Centre, University Hospitals Southampton NHS Foundation Trust, Southampton, UK).