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.

The use of whole-exome sequencing to disentangle complex phenotypes

“…The potential to improve the prognosis of such patients makes the use of WES a very cost-effective strategy in the clinic. 15 …”

Diagnostic Methods in Primary Ciliary Dyskinesia

“…Moreover there is no global agreement regarding the standardisation of conduct or reporting of any of the methods used to diagnose PCD. Diagnosis in Europe is generally based on the following criteria [11,15,17,18]: in a person with a clinical history consistent with PCD confirmation of the diagnosis by at least two of the following methods: (1) "hallmark" high speed videomicroscopy analysis (HVMA), (2) "hallmark" TEM, (3) biallellic disease-causing mutations identified by gene testing, (4) abnormally low nasal nitric oxide (nNO). If HVMA and nNO are the only abnormal tests, these tests should be repeated before making a diagnosis.…”

“…Whilst the reason for reduced nNO remains elusive [27], measurement became widely established as a screening test [11,17,19,[28][29][30][31]. A recent meta-A c c e p t e d M a n u s c r i p t analysis of 11 studies comparing nNO during a velum closure breath hold reported a mean nNO output of 19 nl/min (SD 18.6) in PCD (n=478) and 265 nl/min (SD 118.9) in healthy controls (n=338) [32].…”

“…Although assessment of ciliary function by light microscopy is recognised as a critical diagnostic test used as 'first-line' in many centres [11,17,48,53,54,56] it should be noted that some clinicians question its value and recommend that HVMA should be reserved for research purposes [20]. A limitation of HVMA is the need for specialist equipment, rigorous quality control and experienced technicians with a high through-put of normal and abnormal samples.…”

“…National collaborations are contributing to improved diagnostic management in a number of individual countries including France [58,106], and the United Kingdom [17,107].…”