Primary Ciliary Dyskinesia Week

General Information

PCD Week

Primary ciliary dyskinesia is a genetically heterogeneous disorder, and mutations in any protein that is involved in ciliary assembly, structure, or function could theoretically cause disease.  It occurs in roughly 1 in 12,000 to 20,000 live births, based on the prevalence of situs inversus totalis and bronchiectasis in population surveys.  Primary ciliary dyskinesia has been reported in many ethnic groups without apparent racial or gender predilection. In most families, the disease is transmitted by an autosomal-recessive pattern of inheritance.  Parents of affected children are normal and have no evidence of impaired ciliary structure or function.  To date, mutations in 37 different genes have been linked to primary ciliary dyskinesia.

Most patients with primary ciliary dyskinesia present as term babies with neonatal respiratory distress, typically manifested by tachypnea, hypoxemia, or even respiratory failure requiring mechanical ventilation.  The upper respiratory tract is almost universally involved in primary ciliary dyskinesia, and persistent rhinosinusitis is common during infancy.  Inadequate innate mucus clearance leads to chronic sinusitis.  Middle ear disease occurs in nearly all children with primary ciliary dyskinesia, with varying degrees of chronic otitis media leading that can lead to hearing loss.  Impaired mucociliary clearance of the lower respiratory tract leads to daily productive cough that begins early in life, secondary to chronic bronchitis and bronchiectasis.  Left-right laterality defects, such as situs inversus totalis, are found in half of all individuals with primary ciliary dyskinesia with transposition of the thoracic and abdominal organs, also known as Kartagener syndrome.  Through research, we now have greater understanding of the natural history of respiratory tract involvement, and genotype-phenotype relationships are emerging.

The diagnosis of PCD should be suspected in children with chronic or recurring upper and lower respiratory tract symptoms.  Historically, the diagnosis has been based on the presence of characteristic clinical phenotype and ultrastructural defects of cilia, though this approach has limitations as a diagnostic tool.  Recent advances in the understanding of the basic biology and function of the cilium have led to alternative diagnostic tests, including nasal nitric oxide measurements and high-speed videomicroscopy.  Most promising, the identification of disease-causing mutations has led to the development of comprehensive genetic testing that may ultimately overcome many of the current diagnostic limitations.

The ATS and its Public Advisory Roundtable are committed to the concept that research will lead to cures.  These advances will depend on education, advocacy and research partnerships to be formed among patients, parents, clinicians and scientists.  Increased research funding will allow us to better understand the pathophysiology of primary ciliary dyskinesia and potentially identify novel therapeutic targets, which will allow us advance treatments for the many patients and families we serve.

Four Facts About Primary Ciliary Dyskinesia

  1. PCD is an inherited disorder of cilia, the hair-like moving structures that line the airways and help keep them free from debris and infection.
  2. PCD is an ‘autosomal recessive’ disorder (both parents must carry a disease-causing mutation on the same gene) and there are currently 37 genes associated with PCD.
  3. Cilia are also important in determining organ placement and 50% of all individuals with PCD will have unusual organ-placement—either completely reversed organs or situs inversus (PCD with situs inversus is also known as ‘Kartagener syndrome’) or issues with the formation and/or placement of single organs (aka ‘situs ambiguus’). Congenital heart defects are 200X more common in individuals with PCD and situs ambiguus than in the general population.
  4. Bronchiectasis, permanent damage to the airways, is universal in PCD and develops in all patients by adulthood. Bronchiectasis is the most serious complication of PCD, leading to need for lung transplant and/or respiratory failure in some patients.