Primary Ciliary Dyskinesia Week

General Information


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 has been estimated to occur in 1 in 10,000 to 30,000 live births. Primary ciliary dyskinesia has been reported across 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 40 different genes have been linked to primary ciliary dyskinesia.

Most patients with primary ciliary dyskinesia present as term babies with neonatal respiratory distress during the first day of life, 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. 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. Left-right laterality defects, such as situs inversus totalis, are found in half of all affected individuals 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 primary ciliary dyskinesia should be suspected in children who have in infants and children with unexplained neonatal respiratory distress in term newborns, daily year-round productive (wet) cough that begins early in life, persistent rhinosinusitis since early infancy, or left-right laterality defects. Historically, the diagnosis has been based on the presence of characteristic clinical phenotype and ultrastructural defects of cilia, though transmission electron microscopy 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. With the identification of a growing number of primary ciliary dyskinesia-associated genes, genetic testing increasingly has become a viable diagnostic approach. Bialleleic, disease-causing mutations in known genes have been found in more than 70% of known cases.  In 2018, ATS guidelines for diagnosing PCD were published in the American Journal of Respiratory and Critical Care Medicine.

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. Nasal nitric oxide (nNO) is an excellent screening test for PCD. For reasons yet unknown, most individuals with PCD have very low levels of nNO and, when done correctly using validated SOPs, nNO can be very helpful in distinguishing PCD from other disorders.

  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.