PCD diagnosis has historically been a daunting task, relying primarily on interpretation of ciliary ultrastructural biopsies. Recent advancement in our knowledge about PCD genetics and the emergence of a characteristic phenotype for most cases of PCD has greatly improved PCD diagnosis.
ATS Clinical Practice Guideline for the Diagnosis of PCD is now (freely) available at the American Thoracic Society website! Using rigorous evidence-based analysis, this document provides an overview of available information related to best practices for diagnosing PCD and addresses some of the challenges and misinformation currently confronting clinicians and patients in their PCD diagnostic journey
From the PCDF Consensus Statement: “PCD is a rare disorder; consequently, only a limited number of centers have extensive experience in the diagnosis and management of PCD. Research over the past decade has led to a revolution in diagnostic approaches, including nNO and genetic testing. Nevertheless, many PCD patients are still undiagnosed or misdiagnosed. To date, only limited studies have addressed management of PCD, and there have been no large, randomized clinical trials to direct therapy. Therefore, this review article includes consensus recommendations from PCD physicians in North America for diagnosis, monitoring and management of PCD.”
Diagnosis of PCD presents a number of challenges and can often be a complex process. It is not uncommon for the diagnosis to be significantly delayed, with the diagnosis not even considered for many years, after many visits to multiple specialists. Even when PCD is part of the diagnostic workup, inconclusive results may present additional challenges and frustrations. Perhaps the biggest challenge is that there is no single diagnostic testing option that is 100% effective. There are currently only two approved methods for diagnosing PCD:
- Biopsy of ciliated tissue (usually from the nose or trachea) with analysis of ciliary ultrastructure
- Genetic test showing two mutations known to cause PCD—one from each parent
There are three additional tests that can be used as screening tools to determine whether PCD is a likely diagnosis. None of these tests are approved for diagnosis (in the United States at least) and they all must be confirmed by one of the above tests before a diagnosis can be made. These ‘adjunct’ PCD tests are primarily used in research settings:
- Nasal nitric oxide (note: not ‘nitrous’) measurement
- High-speed videomicroscopy to assess ciliary beat pattern
- Immunofluorescent assay using tagged antibodies
Most importantly, there is a strong clinical phenotype—or physical presentation—associated with PCD and diagnostic testing undertaken in the absence of this presentation is not recommended, as it has led to an unacceptably high rate of false positive diagnoses in PCD (people being told they have the disorder when they do not).
With rare exceptions, people with PCD exhibit the following symptoms:
In the first months of life (an important phenotypic feature is that the symptoms of PCD almost always present at birth or shortly after–this can help distinguish PCD from non-PCD):
- Respiratory problems in the newborn period despite full term birth
- Daily, year-round, wet cough starting in the first year of life (usually first months of life) that does not go away with change of seasons. It may improve with antibiotic treatment, but never fully resolves
- Daily, year-round nasal congestion starting in the first year of year of life (usually first months of life) that does not go away with change of seasons
- Any laterality/situs (organ placement) anomaly and/or organ development issue, plus the above
In older children and adults, all of the above remain constant, plus:
- Development of chronic otitis media with effusion and/or recurrent ear infections
- Development of chronic pansinusitis (all sinuses involved)
- Bronchiectasis on chest CT scan or x-ray
- Fertility issues
Expert Centers for PCD Diagnosis
Because PCD diagnosis relies on a high level of experience with the disorder and with diagnostic technologies, the PCD Foundation recommends that diagnosis be done–when at all possible–at a PCD Clinical and Research Network site. Learn more about our PCDF Clinical Centers Network.
Genetic Testing Resources
There are a number of options for genetic testing for PCD, including genetic laboratory services at individual academic sites and commercial genetic testing vendors. Individual physician preference and insurance requirements often dictate which genetic testing provider is used. The list below represents commercial vendors* (vs. in-house academic labs) that offer PCD genetic testing panels.
PLEASE NOTE: This information is provided as an informational resource only and should not be viewed as an endorsement for any particular test or vendor.
- Ambry Genetics: http://www.ambrygen.com/
- Fulgent Diagnostics: https://www.fulgentgenetics.com/
- Invitae: https://www.invitae.com/en/
- McLendon Clinical Laboratory: http://www.uncmedicalcenter.org/mclendon-clinical-laboratories/available-tests/primary-ciliary-dyskinesia-pcd-mutation-testing/
- Prevention Genetics: https://www.preventiongenetics.com/
*Vendors—if you would like to be included on this list, please forward information to the PCD Foundation at firstname.lastname@example.org.