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Kartagener Syndrome

  • Author: John P Bent, III, MD; Chief Editor: Ryland P Byrd, Jr, MD  more...
Updated: Feb 28, 2014


Siewert first described the combination of situs inversus, chronic sinusitis, and bronchiectasis in 1904.[1] However, Manes Kartagener[1] first recognized this clinical triad as a distinct congenital syndrome in 1933. Because Kartagener described this syndrome in detail, it bears his name. Kartagener syndrome (KS) is inherited via an autosomal recessive pattern. Symptoms result from defective cilia motility.

Also see Primary Ciliary Dyskinesia.



Camner and coworkers[2] first suggested ciliary dyskinesia as the cause of Kartagener syndrome in 1975. They described 2 patients with Kartagener syndrome who had immotile cilia and immotile spermatozoa. These patients had poor mucociliary clearance because the cilia that lined their upper airways were not functioning.

Later, Afzelius[3] discovered that bronchial mucosal biopsy specimens from patients with similar respiratory complaints showed cilia that appeared abnormal, were poorly mobile, and were . In 1977, Eliasson and coworkers[4] used the descriptive phrase immotile cilia syndrome to characterize male patients with sterility and chronic respiratory infections. The image below illustrates missing dynein arms in Kartagener syndrome.

Normal cilia (A) compared with cilia in Kartagener Normal cilia (A) compared with cilia in Kartagener syndrome with missing dynein arms (B). Image courtesy of Wikimedia Commons.

In 1981, Rossman and coworkers[5] coined the term primary ciliary dyskinesia (PCD) because some patients with Kartagener syndrome had cilia that were not immobile but exhibited an uncoordinated and inefficient movement pattern. Current nomenclature classifies all congenital ciliary disorders as primary ciliary dyskinesias in order to differentiate them from acquired types. Kartagener syndrome is part of the larger group of disorders referred to as primary ciliary dyskinesias. Approximately one half of patients with primary ciliary dyskinesia have situs inversus and, thus, are classified as having Kartagener syndrome. Afzelius proposed that normal ciliary beating is necessary for visceral rotation during embryonic development. In patients with primary ciliary dyskinesia, organ rotation occurs as a random event; therefore, half the patients have situs inversus and the other half have normal situs.

Ciliated epithelium covers most areas of the upper respiratory tract, including the nasal mucosa, paranasal sinuses, middle ear, eustachian tube, and pharynx. The lower respiratory tract contains ciliated epithelium from the trachea to the respiratory bronchioles. Each ciliated cell gives rise to approximately 200 cilia that vary in length from 5-6 μm and decrease in size as the airway becomes smaller.

The typical ciliary axoneme consists of 2 central microtubules surrounded by 9 microtubular doublets. Each doublet has an A subunit and a B subunit attached as a semicircle. A central sheath envelops the 2 central microtubules, which attach to the outer doublets by radial spokes.

The outer doublets are interconnected by nexin links, and each A subunit is attached to 2 dynein arms that contain adenosine triphosphatase; one inner arm and one outer arm. The primary function of the central sheath, radial spokes, and nexin links is to maintain the structural integrity of the cilium, whereas the dynein arms are responsible for ciliary motion.

The cilium is anchored at its base by cytoplasmic microtubules and a basal body comprised of a basal foot and rootlet. The orientation of the basal foot indicates the direction of the effective cilial stroke. Just above the base, the cilium is composed of microtubular triplets (previously doublets) without associated structures, but at the tip, only the B subunits remain.

Cilia propel overlying mucus via a 2-part ciliary beat cycle. First, the power stroke occurs when a fully extended cilium moves perpendicular to the cell surface in an arclike manner. Then, the recovery stroke follows, in which the entire cilium bends and returns to its starting point near the cell surface. Once a cilium starts to move, the complete beat cycle is obligatory.

The cycle is mediated by dynein arms from the A subunit that attach to the B subunit of the adjacent microtubule. Adenosine triphosphate is hydrolyzed by the dynein arms and the 9 microtubule doublets as they slide against each other.

Patients with primary ciliary dyskinesia exhibit a wide range of defects in ciliary ultrastructure and motility, which ultimately impairs ciliary beating and mucociliary clearance. The most common defect, first described by Afzelius, is a reduction in the number of dynein arms, which decreases the ciliary beat frequency.

Sturgess et al[6] described how the radial spoke, which serves to translate outer microtubular sliding into cilial bending, was absent in some patients with primary ciliary dyskinesia. Cilia in other patients lacked central tubules; however, instead of the central tubules, an outer microtubular doublet transposed to the cell of the axoneme was present that displayed an abnormal 8+1 doublet-to-tubule pattern. Both the radial spoke and the transposed doublet defects impaired mucociliary clearance.

Other ciliary defects include an abnormal basal cell apparatus with giant roots and double feet, cilia lacking all internal microtubular structures, and even cilia twice the normal length that beat in an uncoordinated undulating fashion. Pedersen[7] compared the type of ultrastructural defect to ciliary motility and found that dynein defects caused hypomotility and microtubular defects caused asynchrony. He also found that normal ciliary ultrastructure occasionally was associated with hypermotility or inefficient ciliary trembling.

Some patients with clinical features of primary ciliary dyskinesia have a ciliary ultrastructure that appears normal, but their arrangement and beat direction is disoriented, which causes inefficient mucociliary transport. These findings illustrate the importance of analyzing ciliary motility and ultrastructure when considering a diagnosis of primary ciliary dyskinesia.

PCD tissues have also been characterized by impaired chloride ion transport currents. This impaired current has been shown to persist even after application of a cAMP-elevating agonist.[8]




United States

The frequency of Kartagener syndrome is 1 case per 32,000 live births. Situs inversus occurs randomly in half the patients with primary ciliary dyskinesia; therefore, for every patient with Kartagener syndrome, another patient has primary ciliary dyskinesia but not situs inversus.


Clinical manifestations include chronic upper and lower respiratory tract disease resulting from ineffective mucociliary clearance. Males demonstrate infertility secondary to immotile spermatozoa.

Upper airway

Patients may exhibit chronic, thick, mucoid rhinorrhea from early in childhood. Examination usually reveals pale and swollen nasal mucosa, mucopurulent secretions, and an impaired sense of smell. Nasal polyps are recognized in 30% of affected individuals.

Sinonasal disease in PCD is poorly studied; however, these patients often have recurrent chronic sinusitis with sinus pressure headaches in the maxillary and periorbital regions. Sinus radiographs (which largely have been supplanted by CT scans) typically demonstrate mucosal thickening, opacified sinus cavities, and aplastic or hypoplastic frontal and/or sphenoid sinuses.[9] Symptoms usually improve with antibiotic therapy but have a propensity for rapid recurrence. It appears that patients with chronic rhinosinusitis (CRS) may benefit from long-term macrolide therapy and endoscopic sinus surgery (ESS) in recalcitrant disease. Therapies targeted at improving mucociliary clearance have not been tested specifically in PCD.[10] It has been shown that up to 59% of patients have recurring problems at the paranasal sinuses and 69% of these patients need corresponding surgical intervention.[11]

Recurrent otitis media is a common manifestation of primary ciliary dyskinesia. Examination may reveal a retracted tympanic membrane with poor or absent mobility and a middle-ear effusion. Further testing usually demonstrates a flat tympanogram and bilateral conductive hearing loss secondary to thick middle-ear effusion. Many patients undergo repeated tympanostomy tube insertion, often complicated by chronic suppurative otitis media. Campbell et al found that ventilation tube insertion improves hearing in PCD, but may lead to a higher rate of otorrhea when compared with the general population.[10] Other associated otologic disorders may include tympanosclerosis, cholesteatoma, and keratosis obturans.

Lower respiratory tract

Chronic bronchitis, recurrent pneumonia, and bronchiectasis are common conditions associated with primary ciliary dyskinesia. Patients presenting with bronchiectasis should be evaluated for Kartagener syndrome. Bronchiectasis usually occurs in the lower lobes in patients with Kartagener syndrome, while patients with cystic fibrosis have bronchiectasis predominantly in the upper lobes.

Chest radiographs may illustrate bronchial wall thickening (earliest manifestation), hyperinflation, atelectasis, bronchiectasis, and situs inversus (in 50% of patients with PCD). High-resolution CT (HRCT) scanning, spirometry, and plethysmography may also be performed. Pifferi et al found that plethysmography better predicted HRCT abnormalities than spirometry by allowing recognition of different severities of focal air trapping, atelectasis, and extent of bronchiectasis in patients with PCD. Whether it might be a useful test to define populations of patients with PCD who should or should not have HRCT scans requires further longitudinal studies.[12] Magnin et al evaluated the longitudinal relationships between lung function tests (LFTs) and chest HRCT in children with PCD and found significant correlation. It is possible that lung function follow-up can be used to adjust CT frequency to help minimize the radiation exposure in these children.[13]

Obstructive lung disease may be another component of Kartagener syndrome symptomatology. It probably results from elevated levels of local inflammatory mediators in a chronically irritated airway.

Other features

Other features include digital clubbing and diminished female fertility. Primary ciliary dyskinesia has been associated with esophageal problems and congenital cardiac abnormalities.


No sex predilection exists.


Clinical manifestations of chronic sinusitis, bronchitis, and bronchiectasis are more severe during the first decade of life but remit somewhat by the end of adolescence.

Contributor Information and Disclosures

John P Bent, III, MD Professor, Director of Pediatric Otolaryngology, Departments of Otolaryngology-Head and Neck Surgery and Pediatrics, Albert Einstein School of Medicine; Director, Airway Clinic, Cochlear Implant Program, Children's Hospital at Montefiore

John P Bent, III, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, Society of University Otolaryngologists-Head and Neck Surgeons, American Society of Pediatric Otolaryngology, Society for Ear, Nose and Throat Advances in Children, Triological Society

Disclosure: Nothing to disclose.


Elena B Willis, MD Resident Physician, Department of Otorhinolaryngology, Albert Einstein College of Medicine, Montefiore Medical Center

Elena B Willis, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Medical Student Association/Foundation, Wilderness Medical Society

Disclosure: Nothing to disclose.

Arvind K Badhey, MD Resident Physician, Department of Otolaryngology, Icahn School of Medicine at Mount Sinai

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Daniel R Ouellette, MD, FCCP Associate Professor of Medicine, Wayne State University School of Medicine; Chair of the Clinical Competency Committee, Pulmonary and Critical Care Fellowship Program, Senior Staff and Attending Physician, Division of Pulmonary and Critical Care Medicine, Henry Ford Health System; Chair, Guideline Oversight Committee, American College of Chest Physicians

Daniel R Ouellette, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, Society of Critical Care Medicine, American Thoracic Society

Disclosure: Nothing to disclose.

Chief Editor

Ryland P Byrd, Jr, MD Professor of Medicine, Division of Pulmonary Disease and Critical Care Medicine, James H Quillen College of Medicine, East Tennessee State University

Ryland P Byrd, Jr, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Additional Contributors

Ryland P Byrd, Jr, MD Professor of Medicine, Division of Pulmonary Disease and Critical Care Medicine, James H Quillen College of Medicine, East Tennessee State University

Ryland P Byrd, Jr, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Matthew Olearczyk, MD and Esther X Vivas, MD, to the development and writing of this article.

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Axial CT image showing dextrocardia and situs inversus in a patient with Kartagener syndrome. Image courtesy of Wikimedia Commons.
Axial CT image showing situs inversus (liver and inferior vena cava on the left, spleen and aorta on the right) in a patient with Kartagener syndrome. Image courtesy of Wikimedia Commons.
Normal cilia (A) compared with cilia in Kartagener syndrome with missing dynein arms (B). Image courtesy of Wikimedia Commons.
Table. Mutations in the Genes that Cause Human Primary Ciliary Dyskinesia [14]
Human Gene Human Chromosomal Location Chlamydomonas Ortholog Ciliary Ultrastructure in Subjects with Biallelic Mutations Presence of Laterality Defects Percentage of Individual with Biallelic Mutations MIM No.
DNAH5 5p15.2 DHC ? ODA defect Yes 15–21% of all PCD, 27–38% of PCD with ODA defects 608644
DNAI1 9p21-p13 IC78 ODA defect Yes 2–9% of all PCD, 4–13% of PCD with ODA defects 244400
DNAI2 17q25 IC69 ODA defect Yes 2% of all PCD, 4% of PCD with ODA defects 612444
DNAL1 14q24.3 LC1 ODA defect Yes na 614017
CCDC114 19q13.32 DC2 ODA defect Yes 6% of PCD with ODA defects 615038
TXNDC3 (NME8) 7p14-p13 LC5 Partial ODA defect (66% cilia defective) Yes na 610852
DNAAF1 (LRRC50) 16q24.1 ODA7 ODA + IDA defect Yes 17% of PCD with ODA + IDA defects 613193
DNAAF2 (KTU) 14q21.3 PF13 ODA + IDA defect Yes 12% of PCD with ODA + IDA defects 612517, 612518
DNAAF3 (C19ORF51) 19q13.42 PF22 ODA + IDA defect Yes na 606763
CCDC103 17q21.31 PR46b ODA + IDA defect Yes na 614679
HEATR2 7p22.3 Chlre4 gene model 525994 Phytozyme v8.0 gene ID Cre09.g39500.t1 ODA + IDA defect Yes na 614864
LRRC6 8q24 MOT47 ODA + IDA defect Yes 11% of PCD with ODA + IDA defects 614930
CCDC39 3q26.33 FAP59 IDA defect + axonemal disorganization Yes 36–65% of PCD with IDA defects + Axonemal disorganization 613798
CCDC40 17q25.3 FAP172 IDA defect + axonemal disorganization Yes 24–54% of PCD with IDA defects + Axonemal disorganization 613808
RSPH4A 6q22.1 RSP4, RSP6 Mostly normal, CA defects in small proportion of cilia No na 612649
RSPH9 6p21.1 RSP9 Mostly normal, CA defects in small proportion of cilia No na 612648
HYDIN 16q22.2 hydin Normal, very occasionally CA defects No na 610812
DNAH11 7p21 DHC ß Normal Yes 6% of all PCD, 22% of PCD with normal ultrastructure 603339
RPGR Xp21.1 na Mixed No PCD cosegregates with X-linked Retinitis pigmentosa 300170
OFD1 Xq22 OFD1 nd No PCD cosegregates with X-linked mental retardation 312610
CCDC164 (C2ORF39) 2p23.3 DRC1 Nexin (N-DRC) link missing; axonemal disorganization in small proportion of cilia No na 312610
CA = central apparatus; IDA = inner dynein arm; MIM = Mendelian Inheritance in Man; na = not available; N-DRC = nexin–dynein regulatory complex; ODA = outer dynein arm; PCD = primary ciliary dyskinesia.
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