Primary Ciliary Dyskinesia 

Introduction: Primary Ciliary Dyskinesia (PCD) is a recessive genetic disorder that affects the differentiation and motility functions of cilia in various organs and cells of the human body. The organ system that is primarily affected in this disease is the respiratory system where cilia beat continuously to remove mucus that traps inhaled pollutants and pathogens (Fig. 1).

Prevalence: Current estimate of the occurrence of PCD in the general population is about 1: 10,000 to 1: 20,000, whereas in communities that practice consanguinity the frequency can be much higher (1,2).

Figure 1. Diagram of motile cilia mediated mucus clearance in the airway of a healthy individual. Cilia are the hair-like projections on the multiciliated cells. The cilia beat continuously like a brush to move layers of mucus towards the throat and nose. In PCD patients, these cilia are dysfunctional due to genetic defects in cilia assembly and/or motility. Consequently, mucus clearance is affected, leading to recurrent respiratory infections and damage to the airway.

Cause: PCD arises from mutations in genes that encode proteins required for the formation and function of motile cilia (1). Motile cilia are hair like organelles that project from the surface of specialized epithelial cells (3). Some cells differentiate a single motile cilium, while others have hundreds of them. Motile cilia are able to beat rhythmically, which is why they play important roles in fluid clearance over epithelia or in cellular locomotion. In the human body, motile cilia are present on cells lining the respiratory tract (where, as discussed above, they function to clear mucus that traps inhaled pathogens and pollutants), within the brain ventricles (for circulation of cerebrospinal fluid [CSF]), within the oviducts of women and epididymis of men (where they are required to transport the ova and sperm, respectively) and on the sperm cells themselves (as long flagella, required for sperm propulsion). In addition, during development, the human embryo is thought to have motile cilia in a pit-like cavity called the ventral node. Nodal cilia movement creates an asymmetric fluid flow that is required for initiating asymmetric development of internal organs (like the heart positioned towards the left and the stomach situated on the right) (4). In the absence of this directional flow due to defects in nodal cilia motility, proper positioning of the internal organs can be randomised. Sperm cells and node cells have single motile cilia (single flagellum in case of sperm cells), while cells within the respiratory tract, oviducts, epididymis and brain ventricles have so called multiciliated cells with hundreds of motile cilia.

Reduced Generation of Multiple Motile Cilia: A more recently identified variant of PCD is reduced generation of multiple motile cilia (RGMC). In this disease, respiratory symptoms, hydrocephalus and infertility are the major issues because what is affected is the ability of multiciliated cells to form or for the multiciliated cells to generate sufficient numbers of motile cilia. Organ positioning within the body is not affected because the node cells have single motile cilia which are not affected by the disease. Only two genes have been associated with RGMC – one required for the muticiliated cells to form and the other for these cells to make sufficient numbers of motile cilia. The diagnosis and treatment options for RGMC largely remain the same as for conventional PCD.

Symptoms: PCD is genetically heterogeneous and mutations in more than 30 ciliary genes have been found be causative of this disorder (1). Patients with PCD have clinical symptoms of disease manifest in all the tissues and cells that require motile cilia for their proper functioning and development. Thus, they typically suffer from chronic upper and lower respiratory tract infections due to ineffective mucus clearance leading to bronchiectasis (and permanent lung damage if untreated), chronic middle ear infections, infertility and sometimes hydrocephalus or swelling of the brain ventricles due to improper csf circulation. In addition, about half of PCD patients have developmental anomalies of internal organs called situs inversus (when the internal organs like heart, stomach, spleen etc are all located on the opposite sides; for example, the heart tilted to the right and the stomach on the left) or heterotaxy (when the internal organs are not transposed in a mirror image inversion, but rather scrambled up). Heterotaxy with cardiac abnormalities requires correction via surgical intervention. Respiratory symptoms in PCD patients often present themselves at birth with respiratory distress. Occurrence of respiratory symptoms along with organ positioning defects is a strong indication of PCD. The presentation of respiratory pathology like sinusitis and bronchiectasis along with situs inversus is often called Kartagener syndrome.

Diagnosis: Clinical diagnosis of PCD is challenging (5). Although some symptoms are often apparent at birth such as respiratory distress, definitive diagnosis usually occurs much later in childhood or adulthood, by when the patient has developed significant lung damage. The disease is often confused with cystic fibrosis, asthma and other respiratory disorders. Historically, measurement of nasal nitric oxide (NO) levels and evaluation of ciliary ultrastructure from ciliated cells obtained by brushing of the nasal cavities (or brushing of the bronchi) by electron microscopy have been used to diagnose PCD. While nasal NO levels are typically low in PCD patients, measurement of NO levels is not a reliable diagnostic test, especially in children. Transmission electron microscopy (TEM) to examine defects in ciliary ultrastructure is a much more reliable method, but is a demanding technique that is time-consuming and expensive to be used as a routine diagnostic procedure. Moreover, not all ciliary defects are apparent on TEM analysis. Yet, the importance of early diagnosis of the disease cannot be emphasized enough as this allows for much better prognosis and maintenance of healthy lung conditions in the patients into later life. Without early diagnosis, atelectasis and bronchiectasis usually sets in by teenage and early adult life, resulting in permanent lung damage that can only be rectified with lung transplantation. Most clinics in Europe and America now use high-speed videomicroscopy (HVM) of the nasal ciliated cells as an additional diagnostic test for PCD. HVM is a simple and cost-effective technique that allows for direct visualization of ciliary motility using a compound microscope and a high-speed video camera. This technique not only helps to distinguish motile from immotile cilia, but also differences in ciliary beat frequency as well as ciliary beat pattern can be detected. Defects in both of these parameters can also result in PCD. Once ciliary motility defects are identified, further confirmatory tests are performed using immunofluorescence labelling with antibodies to a variety of ciliary proteins, and then transmission electron microscopy TEM. In addition, X-ray or ultrasound imaging of internal organs like the heart is highly recommended, since as discussed above, the presence of respiratory symptoms along with situs abnormalities significantly raises the suspicion of PCD. Finally, whole exome or whole genome sequencing as well as targeted sequencing of candidate gene/s leads to the identification of the underlying mutation.

Treatment: Currently, there is no cure for PCD. However, early diagnosis clearly helps to maintain a good quality of life among affected individuals. Otherwise, the respiratory system can get so badly damaged that lung transplantation will remain the only option. The key is to maintain the health of the airways by aggressive antibiotic treatments on infection, physiotherapy to regularly clear mucus, and timely administration of appropriate health vaccines (6). Cardiac anomalies must be corrected by appropriate surgical intervention. Infertility issues can be effectively dealt with using in vitro fertilization. It is expected that the various forms of genome editing technologies that are rapidly evolving at the moment, may become useful for gene therapy strategies in the future.

PCD in the regional context: Much of what we know about the genetics and pathology of PCD has come from studies with patients from North America, Europe and West Eurasian countries (and migrant Asian populations residing in these regions). More recently, PCD reports are appearing from China and Japan. From India, there have been a number of case reports of Kartagener syndrome patients. There is no clinic currently available in the country equipped to make a formal diagnosis of PCD.

PCD historical information: The role of abnormal cilia in the pathogenesis of PCD was first identified in the 1970s through TEM analysis of respiratory cilia obtained from Kartagener syndrome patients (7,8). Mutations in DNAH5, the first gene responsible for PCD and encoding a major dynein protein of cilia, were reported in 2002 (9). Since 2006, with advancements in genomic technologies, there has been a rapid identification of mutations is a large number of additional genes responsible for PCD. 


1. Primary Ciliary Dyskinesia. Knowles MR, Zariwala M, Leigh M. Clin Chest Med. 2016; 37:449-61.

2. High prevalence of primary ciliary dyskinesia in a British Asian population. O'Callaghan C, Chetcuti P, Moya E. Arch Dis Child. 2010; 95:51-2.

3. SnapShot: Motile Cilia. Zhou F, Roy S. Cell 2015; 162:224-224.

4. Left-right asymmetry: cilia stir up new surprises in the node. Babu D, Roy S. Open Biol. 2013; 3:130052.

5. Diagnosis of primary ciliary dyskinesia: potential options for resource-limited countries. Rumman N, Jackson C, Collins S, Goggin P, Coles J, Lucas JS. Eur Respir Rev. 2017; 26(143).

6. Treatment recommendations in Primary Ciliary Dyskinesia. Polineni D, Davis SD, Dell SD. Paediatr Respir Rev. 2016; 18:39-45.

7. A human syndrome caused by immotile cilia. Afzelius BA. Science 1976; 193:317-9.

8. Absence of axonemal arms in nasal mucosa cilia in Kartagener's syndrome. Pedersen H, Mygind N. Nature 1976; 262:494-5.

9. Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetry. Olbrich H, Häffner K, Kispert A, Völkel A, Volz A, Sasmaz G, Reinhardt R, Hennig S, Lehrach H, Konietzko N, Zariwala M, Noone PG, Knowles M, Mitchison HM, Meeks M, Chung EM, Hildebrandt F, Sudbrak R, Omran H. Nat Genet. 2002; 30:143-4.

Resources for patients and clinicians: 

1. 2. 3.


Sudipto Roy PhD
Senior Principal Investigator
Institute of Molecular and Cell Biology
Agency for Science, Technology and Research (A*STAR)
Proteos, 61 Biopolis Drive
Singapore, 138673

Mohammad Khan MD, PhD
Children's Hospital of Philadelphia
University of Pennsylvania, Philadelphia, PA, USA

February 2017