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Primary ciliary dyskinesia (PCD) is a rare, inherited disorder that disrupts the body’s ability to clear mucus and secretions from the airways and other organs lined by ciliated epithelium.[1] This is because it affects the structure and function of motile cilia that are part of the epithelium. The condition results from various genetic mutations, which disrupt normal ciliary function. Dysfunctional ciliary motion leads to chronic respiratory infections, sinus disease, middle-ear effusion, and, in roughly half of patients, abnormal organ positioning known as situs inversus (e.g., dextrocardia).[2]
PCD is not the same as secondary ciliary dyskinesia (SCD), which is temporary and occurs during or after an acute respiratory infection or results from environmental toxin exposure (e.g., chronic tobacco smoking, chronic inflammation). In contrast, PCD is a lifelong disease and results from intrinsic structural or functional defects of the cilia.
Historically, the combination of situs inversus, chronic sinusitis, and bronchiectasis was termed Kartagener syndrome, described in 1933.[3] It is now recognized as a classic clinical subset of primary ciliary dyskinesia.
Epidemiology of Primary Ciliary Dyskinesia
PCD affects all populations irrespective of gender, at a rate of 1 in every 10,000 to 30,000 people.[4] This is not to mention that the condition remains undiagnosed or underdiagnosed in many low-resource regions. And, the overlap of its symptoms with asthma, chronic sinusitis, or cystic fibrosis (CF) adds to this underdiagnosis.
Sometimes PCD is clear enough for diagnosis in early infancy, but the average age of diagnosis is often after age 5, and many adults are only diagnosed retrospectively when chronic bronchiectasis is investigated.
In countries where cousin marriages are common, the rates are a bit higher because the condition is inherited in an autosomal recessive way, meaning you need two faulty copies of the gene.
Pathophysiology of Primary Ciliary Dyskinesia
Ciliated epithelium lines the airways, sinuses, ears, and even reproductive organs. A normal cilium has a “9 + 2” microtubule arrangement: nine outer doublets surrounding two central microtubules, connected by dynein arms that generate coordinated beating movements. In PCD, genetic mutations target this structure.[5]
Overall, at least 50 genes have been implicated, including DNAH5, DNAI1, CCDC39, CCDC40, and RSPH1, each targeting a specific structural component. Not all mutations are equal, though; certain genotypes (e.g., CCDC39/40) are associated with early and more severe lung disease.[6]
Ciliary cross-sections from nasal brushings: (A) In normal cilia, the 9+2 axonemal structure is visible, with outer (green) and inner (magenta) dynein arms, a central pair (yellow), and radial spokes (blue). (B) In contrast, dynein arm defects show truncation or absence of the outer and/or inner arms. (C) Additionally, some axonemes demonstrate combined inner arm loss with microtubular disorganisation and a misplaced doublet. (D) Finally, secondary defects may involve the central pair, appearing as absent, duplicated, or disoriented microtubules (Image Courtesy: Birkhead, M., Otido, S., Mabaso, T., Mopeli, K., Tlhapi, D., Verwey, C., & Dangor, Z. (2023). Ultrastructure for the diagnosis of primary ciliary dyskinesia in South Africa, a resource-limited setting. Frontiers in Pediatrics, 11, 1247638. Available fromFrontiersand licensed under CC by 4.0)
Respiratory Consequences
Normally, as long as the cilia move rhythmically, they help to move mucus, bacteria, and debris out of the lungs and sinuses. However, because of structural defects in PCD, the cilia move weakly, erratically, or don’t move at all.
That’s why mucus collects in the lungs and bacteria get the chance to thrive and cause repeated infections. People with PCD often have repeated chest infections, chronic sinusitis, and ear problems right from early childhood. Persistent infections obviously damage the airways and eventually lead to bronchiectasis.
Proposed mechanism of chronic inflammation in primary ciliary dyskinesia: (1) Because of ciliary immotility, mucus is not cleared effectively, allowing pathogens to persist in the airways. (2) As a result, these pathogens trigger inflammation and attract neutrophils, which become activated during migration. (3) The activated neutrophils release enzymes and form neutrophil extracellular traps (NETs) to control infection. (4) However, due to impaired clearance, apoptotic cells, DNA, and enzymes accumulate in the airways. (5) These proteases interfere with macrophage activity and delay resolution of inflammation. (6) Ultimately, the persistent neutrophil products damage airway cells, thereby worsening inflammation and increasing susceptibility to secondary infection (Image Courtesy: Blanter, M., Cockx, M., Wittebols, L. et al. Sputum from patients with primary ciliary dyskinesia contains high numbers of dysfunctional neutrophils and inhibits efferocytosis. Respir Res 23, 359 (2022). Available fromBMCand licensed under CC by 4.0)
Ciliary Function in Organ Development
During early development, flow of the motile nodal cilia in the embryo determines which side of the body your organs are going to be developed on (usually left-right orientation).[7] It’s obvious then that when these are defective, this entire flow is disturbed, the arrangement is random.
- Situs inversus totalis (mirror-image organ arrangement) in about 50% of patients
- Heterotaxy syndromes (partial or inconsistent organ arrangement) in about 6–10%
Reproductive System and ENT Involvement
Ciliary dyskinesia also results in immotile sperm in males, and reciprocally, dysfunctional fallopian tube cilia in females, which means almost certain infertility or subfertility.
On the ENT front, PCD causes middle ear disease: defective eustachian tube clearance can cause otitis media and conductive hearing loss.
Primary Ciliary Dyskinesia Symptoms
PCD symptoms show up early, often in the neonatal period, and involves multiple organ systems. Its symptoms are classically chronic, progressive, and recurring. The exact severity of the symptoms varies from case to case; some people have very prominent symptoms in their early life, while some only experience mild symptoms later on.[8]
Respiratory Tract
Neonatal respiratory distress in full-term infants without a clear cause is one of the earliest signs. Other than that:
- Chronic, productive cough starting from infancy, often daily
- Repeated chest infections and pneumonia
- Shortness of breath and reduced exercise tolerance in advanced disease
Eyes, Nose, and Throat
- Chronic nasal congestion and a runny nose
- Recurrent otitis media with effusion (“glue ear”)
- Conductive hearing loss, especially in children
- Chronic sinusitis, sometimes with nasal polyps
Reproductive System
- Fertility issues in both men and women: male infertility due to immotile sperm, and female subfertility due to poor oocyte transport
- Normal hormonal and secondary sexual characteristics
These symptoms are general enough that they can easily mimic or overlap with other chronic airway diseases, naturally leading to a delay in diagnoses.
Primary Ciliary Dyskinesia Types
PCD can be classified based on the ultrastructural defect observed on transmission electron microscopy (TEM) and correlated with gene mutations.[9]
| Ultrastructural Defect | Mutated Genes | Clinical Notes |
|---|---|---|
| Outer dynein arm (ODA) defects | DNAH5, DNAI1 | Classic phenotype; often with situs inversus |
| Combined ODA + inner dynein arm (IDA) defects | CCDC39, CCDC40 | More severe lung disease, early bronchiectasis |
| Central pair or radial spoke defects | RSPH1, HYDIN | Normal organ situs, milder disease |
| ODA-docking complex defects | ARMC4, CCDC114 | Variable severity |
| Normal TEM (functional defect) | DNAH11, HYDIN | Functional but not ultrastructural abnormality; requires video microscopy or genetic confirmation |
Primary Ciliary Dyskinesia Diagnosis
No single test is actually enough to confirm or rule out dyskinesia.For acurate PCD diagnosis, clinicians look for a compatible clinical picture along with enough confirmatory evidence from testing. The final interpretation should always be multidisciplinary within an experienced PCD diagnostic center.
1. Clinical Suspicion
PCD should be suspected when at least two of the following are observed:
- History of daily, consistent, wet cough since early infancy
- Chronic nasal congestion
- In a term infant, unexplained neonatal respiratory distress
- Situs inversus
- Family history of PCD or unexplained bronchiectasis
Once suspected, proper scoring systems like PICADAR[10] can determine the exact likelihood of PCD and how to proceed with further testing.
2. Screening Tests
Nasal Nitric Oxide Testing: This test involves measuring the levels of nitric oxide when a person breathes out. In PCD, it is markedly reduced (<77 nL/min). Since the process is non-invasive, this test is useful as a first-line screening tool. A value within the normal limits essentially excludes PCD, except in very young children.[11]
3. Confirmatory Testing
- High-speed video microscopy involves viewing the movement of the cilia under a microscope in a sample that the pulmonologist collects from the nose or from bronchial brushings.
- Transmission electron microscopy identifies structural abnormalities (e.g., absent dynein arms, disorganized microtubules) in the cilia, as well as whether they’re working well.
- Immunofluorescence detects the absence or mislocalization of specific ciliary proteins such as DNAH5 or RSPH4A.
- Genetic testing with next-generation or whole-exome sequencing confirms if there are pathogenic mutations in any of the known PCD genes.
- Imaging studies visualize damage to the airways because of persistent infections. Chest radiographs may show hyperinflation or situs inversus.
The diagnosis tests for Primary Ciliary Dyskinesia often include nasal nitric oxide measurement, electron microscopy, and genetic analysis to identify the specific mutations responsible for ciliary dysfunction. The ICD-10 code for Primary Ciliary Dyskinesia is Q33.8, which helps standardize its documentation in medical records.
Clinical features of primary ciliary dyskinesia (PCD): (A) Coronal CT scan of a 17-year-old with PCD showing diffuse pansinusitis with marked mucosal thickening and nasal polyposis (B) Corresponding endoscopic view demonstrates a nasal polyp in the same patient (C) Chest X-ray of a 6-year-old with PCD reveals middle lobeatelectasis, with silhouetting of the right heart border (D) Meanwhile, chest CT of another 6-year-old with situs inversus totalis shows extensive bronchiectasis and volume loss in the left-sided middle lobe (white arrow), along with areas of consolidation and mucus impaction in the right upper lobe (Image Courtesy: Werner, C., Onnebrink, J.G. & Omran, H. Diagnosis and management of primary ciliary dyskinesia. Cilia 4, 2 (2015). Available fromBMCand licensed under CC by 4.0)
Primary Ciliary Dyskinesia Treatment
The cilia can obviously not be replaced or fixed. PCD management protocols focus on preventing lung damage, infection control, and complications.
Respiratory Management
- For airway clearance, there’s strong emphasis on daily chest physiotherapy and chest physical therapy, also called chest clapping or percussion, to loosen the mucus and help with clearance. Regular exercise also helps.
- Acute infections are treated with early and aggressive antibiotic therapy based on sputum culture. Common pathogens are Haemophilus influenzae, Staphylococcus aureus, and Pseudomonas aeruginosa in advanced disease. Long-term azithromycin (250–500 mg three times weekly) is shown to reduce flare-ups (BESTCILIA trial).[12] Inhaled antibiotics like tobramycin may be used for chronic Pseudomonas aeruginosa colonisation.
- Bronchodilators are commonly used before a round of chest physical therapy; they help relax the muscles around the airways, opening them, and allow for mucus to be cleared.
- Interestingly, there is no proven benefit for corticosteroids as anti-inflammatory drugs other than for co-existing asthma, that too inhaled.
- Annual flu and pneumococcal vaccines can keep patients protected to some extent.
ENT Management
- Recurrent otitis media can pose a threat to hearing, so regular assessment in children is important. If detected, tympanostomy tubes or hearing aids can be helpful. For cases of chronic rhinosinusitis, saline wash and intranasal anti-inflammatory drugs, and sinus surgery might help short term as well.
Fertility Care
- In men, even if the sperm motility is affected, intracytoplasmic sperm injection is an effective solution. Likewise, in women, IVF (in vitro fertilization) can help overcome subfertility/infertility caused by reduced ciliary motility in fallopian tubes.[13] In either case, genetic counselling should be offered to all affected families.
Advanced Disease
- In end-stage respiratory failure, a lung transplant may be indicated. The success rates and outcomes are quite similar to cystic fibrosis when performed in experienced centers. Likewise, it requires strict infection control and immunosuppression after the transplant.
Monitoring and Follow-Up
- Regular lung function tests (every 6 to 12 months)
- Sputum cultures for microbial surveillance
- Chest imaging (HRCT) every few years to look for worsening bronchiectasis
- Multidisciplinary review including pulmonology, ENT, audiology, and physiotherapy
Primary Ciliary Dyskinesia Life Expectancy
The prognosis overall is good as long as the condition can be detected and diagnosed early. Also important is effective infection control, counselling and asserting the importance of chest physical therapy.
In terms of lung function, adults with proper monitoring have mean FEV₁ in the range of 75–80% predicted, with a 1–2% predicted decline in FEV₁ annually if poorly controlled. It is almost never life-threatening, only if a patient is undiagnosed or diagnosed very late and they develop progressive respiratory failure.
Factors that are known to negatively affect prognosis are: late diagnosis, chronic Pseudomonas infection, recurrent severe infections, and CCDC39/40 mutations.
Prognosis aside, chronic symptoms and daily treatments may still have a significant impact on psychosocial well-being and life situation, and those should definitely be addressed as well.
Primary Ciliary Dyskinesia vs Cystic Fibrosis
Although both disorders affect mucus clearance and the lungs, the difference between Primary Ciliary Dyskinesia and Cystic Fibrosis lies in their underlying mechanisms. PCD is caused by defective ciliary motion, whereas CF results from abnormal chloride transport due to CFTR gene mutations. The main differences are mentioned in the table below:
| Feature | Primary Ciliary Dyskinesia | Cystic Fibrosis14Sankari A, Sharma S. Cystic Fibrosis. [Updated 2024 Dec 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK493206/ |
|---|---|---|
| Genetic defect | Structural or functional ciliary motor protein defect | CFTR chloride channel mutation |
| Mode of inheritance | Autosomal recessive | Autosomal recessive |
| Sweat chloride test | Normal | Elevated |
| Nasal nitric oxide | Very low | Normal or slightly low |
| Laterality defects | Common | Absent |
| Common pathogens | H. influenzae, S. aureus, Pseudomonas | Pseudomonas aeruginosa, Burkholderia cepacia |
| Fertility issues | Sperm immotility, tubal dysfunction | Vas deferens absent, thick cervical mucus |
Final Words
Primary ciliary dyskinesia is an uncommon but clinically significant cause of lifelong respiratory and sinus disease. Public awareness of the disease is still low, though, and diagnosis is often delayed even though the symptoms develop pretty early on. If a clinician can recognize the pattern of chronic wet cough, nasal congestion, otitis media, and situs abnormalities, it can be diagnosed early and targeted care can be provided. With regular airway management, infection control, and multidisciplinary follow-up, most patients maintain good average lung function and a normal lifespan. Research is focused on gene therapy and better diagnostic methods.
References
[1] Despotes, K. A., Zariwala, M. A., Davis, S. D., & Ferkol, T. W. (2023). Primary Ciliary Dyskinesia: A Clinical Review. Cells, 13(11), 974. https://doi.org/10.3390/cells13110974
[2] Knowles, M. R., Daniels, L. A., Davis, S. D., Zariwala, M. A., & Leigh, M. W. (2013). Primary ciliary dyskinesia. Recent advances in diagnostics, genetics, and characterization of clinical disease. American journal of respiratory and critical care medicine, 188(8), 913–922. https://doi.org/10.1164/rccm.201301-0059CI
[3] Knowles, M. R., Daniels, L. A., Davis, S. D., Zariwala, M. A., & Leigh, M. W. (2013). Primary ciliary dyskinesia. Recent advances in diagnostics, genetics, and characterization of clinical disease. American journal of respiratory and critical care medicine, 188(8), 913–922. https://doi.org/10.1164/rccm.201301-0059CI
[4] Despotes, K. A., Zariwala, M. A., Davis, S. D., & Ferkol, T. W. (2023). Primary Ciliary Dyskinesia: A Clinical Review. Cells, 13(11), 974. https://doi.org/10.3390/cells13110974
[5] Horani, A., & Ferkol, T. W. (2018). Advances in the Genetics of Primary Ciliary Dyskinesia: Clinical Implications. Chest, 154(3), 645. https://doi.org/10.1016/j.chest.2018.05.007
[6] Davis, S. D., Ferkol, T. W., Rosenfeld, M., Lee, S., Dell, S. D., Sagel, S. D., Milla, C., Zariwala, M. A., Pittman, J. E., Shapiro, A. J., Carson, J. L., Krischer, J. P., Hazucha, M. J., Cooper, M. L., Knowles, M. R., & Leigh, M. W. (2015). Clinical Features of Childhood Primary Ciliary Dyskinesia by Genotype and Ultrastructural Phenotype. American Journal of Respiratory and Critical Care Medicine, 191(3), 316. https://doi.org/10.1164/rccm.201409-1672OC
[7] Hamada H. Roles of Motile and Immotile Cilia in Left-Right Symmetry Breaking. 2016 Jun 25. In: Nakanishi T, Markwald RR, Baldwin HS, et al., editors. Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology [Internet]. Tokyo: Springer; 2016. Chapter 7. Available from: https://www.ncbi.nlm.nih.gov/books/NBK500261/ doi: 10.1007/978-4-431-54628-3_7
[8] Lavoie, V., Zysman-Colman, Z., & Shapiro, A. J. (2025). Primary ciliary dyskinesia. Paediatrics & Child Health, 30(4), 203. https://doi.org/10.1093/pch/pxae102
[9] Lucas, J. S., Davis, S. D., Omran, H., & Shoemark, A. (2020). Primary ciliary dyskinesia in the genomics age. The Lancet. Respiratory medicine, 8(2), 202–216. https://doi.org/10.1016/S2213-2600(19)30374-1
[10] Behan, L., Dimitrov, B. D., Kuehni, C. E., Hogg, C., Carroll, M., Evans, H. J., Goutaki, M., Harris, A., Packham, S., Walker, W. T., & Lucas, J. S. (2016). PICADAR: A diagnostic predictive tool for primary ciliary dyskinesia. The European Respiratory Journal, 47(4), 1103. https://doi.org/10.1183/13993003.01551-2015
[11] Shapiro, A. J., Davis, S. D., Leigh, M. W., Knowles, M. R., Lavergne, V., & Ferkol, T. (2020). Limitations of Nasal Nitric Oxide Testing in Primary Ciliary Dyskinesia. American journal of respiratory and critical care medicine, 202(3), 476–477. https://doi.org/10.1164/rccm.202003-0835LE
[12] Kobbernagel, H. E., Buchvald, F. F., Haarman, E. G., Casaulta, C., Collins, S. A., Hogg, C., Kuehni, C. E., Lucas, J. S., Moser, C. E., Quittner, A. L., Raidt, J., Rosthøj, S., Sørensen, A. L., Thomsen, K., Werner, C., Omran, H., & Nielsen, K. G. (2020). Efficacy and safety of azithromycin maintenance therapy in primary ciliary dyskinesia (BESTCILIA): a multicentre, double-blind, randomised, placebo-controlled phase 3 trial. The Lancet. Respiratory medicine, 8(5), 493–505. https://doi.org/10.1016/S2213-2600(20)30058-8
[13] Despotes, K. A., Zariwala, M. A., Davis, S. D., & Ferkol, T. W. (2023). Primary Ciliary Dyskinesia: A Clinical Review. Cells, 13(11), 974. https://doi.org/10.3390/cells13110974
[14] Sankari A, Sharma S. Cystic Fibrosis. [Updated 2024 Dec 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK493206/