J Pediatr Genet 2014; 03(02): 115-127
DOI: 10.3233/PGE-14088
Review Article
Georg Thieme Verlag KG Stuttgart – New York

Primary ciliary dyskinesia: From diagnosis to molecular mechanisms

Tamara Paff
a  Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands
b  Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands
c  Department of Pediatric Pulmonology, VU University Medical Center, Amsterdam, The Netherlands
,
Johannes M.A. Daniels
a  Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands
,
Gerard Pals
b  Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands
,
Eric G. Haarman
c  Department of Pediatric Pulmonology, VU University Medical Center, Amsterdam, The Netherlands
› Author Affiliations

Subject Editor:
Further Information

Publication History

02 May 2014

08 June 2014

Publication Date:
27 July 2015 (online)

Abstract

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder affecting motile cilia. This can lead to neonatal respiratory distress, early onset upper and lower airway infections, laterality abnormalities and sub- or infertility. Although disease progression shows large individual variability, all adult patients eventually develop extensive bronchiectasis. As in cystic fibrosis, early diagnosis and frequent follow-up with microbiological control is the best therapeutic strategy, as other treatment options are lacking. PCD is underdiagnosed and diagnosed late due to clinical unawareness, limited availability of diagnostic tests and difficult interpretation of test results. Diagnosis is currently based on a combination of assessment of ciliary motion and ultrastructure by high-speed video microscopy and electron microscopy, respectively. As nasal nitric oxide is low in almost all PCD patients, these measurements can be used for screening. Although there are 26 PCD genes known so far, the genetic basis of the disease has not been unraveled in an estimated 30–40% of patients. However, the rapid discovery of novel PCD genes in recent years is expected to enable accurate genetic characterization of most patients in the near future. Large-scale use of next-generation sequencing and the availability of large ciliary proteomic and transcriptomic databases accelerate the identification of novel PCD genes, especially those that play a key role in cytoplasmic assembly of ciliary ultrastructural components. These genetic advances are revolutionizing the process of obtaining a molecular diagnosis for PCD as we speak and may ultimately lead to an increased understanding of ciliogenesis and function, providing novel handles for therapeutic interventions in PCD patients.