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Kartagener Syndrome Clinical Presentation

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

History

Patients commonly present with chronic upper and lower respiratory tract infections resulting from an ineffective mucociliary mechanism. Patients present initially in the neonatal period, suggestive of ineffective ciliary motion needed to clear fetal lung fluid.

When taking a typical history, pertinent findings include chronic wet cough with unexplained respiratory distress. This cough is described as wet and productive, found in nearly 100% of infants.[14] Coupled with improper drainage of the sinonasal system, this leads to congestion, rhinorrhea, and chronic middle ear effusions with possible purulent otorrhea.

Some male patients present later in life with sterility due to immotile spermatozoa.

Lastly, situs inversus abnormalities on imaging are relatively specific for Kartagener syndrome.[15]

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Physical

Kartagener syndrome is characterized by the clinical triad of chronic sinusitis, bronchiectasis, and situs inversus. The majority of patients are seen by a physician more than 50 times before the diagnosis is made at an average age of 10-14 years.[11]

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.[16]

The recurrent chronic sinusitis typically produces sinus pressure headaches in the maxillary and periorbital region. Symptoms usually improve with antibiotic therapy but have a propensity for rapid recurrence.[16]

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. Other associated otologic disorders may include tympanosclerosis, cholesteatoma, and keratosis obturans.[16]

Middle ear symptoms in PCD patients tend to remain severe throughout childhood, with improvement only after age 18 years, and, in a recent study, grommet tympanostomy tube placement did not improve the middle ear condition. In this study, half the patients with a history of grommet placement eventually developed tympanic perforation, which is much more frequent than in the general pediatric population. These patients, therefore, should be closely followed and a specific treatment approach may be required, especially in the treatment of persistent middle ear effusion, as repeated grommet placement can predispose patients to chronic otitis and worsen the prognosis.[17]

Lower respiratory tract

Chronic bronchitis, recurrent pneumonia, and bronchiectasis are common conditions in patients with primary ciliary dyskinesia and are often caused by pseudomonal infection.[18] Thus, upon physical examination of the patient's chest, increased tactile fremitus, rhonchi, crackles, and, occasionally, wheezes may be present.

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. Therefore, wheezing may occur. The lung examination may be normal during intercurrent periods when the airway is not actively inflamed.

Other features

Cardiovascular examination of a patient with KS demonstrates a point of maximal impulse, and the heart sounds are heard best on the right side of the chest.

Extremities may exhibit digital clubbing.

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Causes

The cause of primary ciliary dyskinesia is genetic, with an autosomal recessive inheritance pattern. Genome analysis has found primary ciliary dyskinesia to be genetically heterogenous. Genes DNAH5 and DNA11 on bands 5p15.1 and 9p13,3 respectively, are known to cause primary ciliary dyskinesia. Both genes encode for dynein.[19] There are more than 200 genes, however, that are predicted to be involved in cilia biology and may play a role in primary ciliary dyskinesia and other ciliopathies.[20]

Recently a gene protein, CCDC40, has been characterized as playing an essential role in correct left-right patterning in mouse, zebrafish, and humans. In mouse and zebrafish, CCDC40 is expressed in tissues that contain motile cilia. Mutations in this protein result in cilia with reduced ranges of motility and likely result in a variant of primary ciliary dyskinesia characterized by misplacement of the central pair of microtubules and defective assembly of inner dynein arms and dynein regulatory complexes.[21]

Onoufriadis et al have described loss-of-function mutations in CCDC114 as causing PCD with laterality malformations. The result of these mutations is a loss of the outer dynein arms. Fertility is apparently not greatly affected by CCDC114 deficiency.[22]

Adenylate kinase type 7 (AK7), the mediator of the reaction of ADP to ATP and AMP, is also diminished significantly in patients with primary ciliary dyskinesia compared with healthy controls. AK7 expression has also been correlated with ciliary beat frequency in this patient population.[23]

Table. Mutations in the Genes that Cause Human Primary Ciliary Dyskinesia[14] (Open Table in a new window)

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.

MIM number is from the Online Mendelian Inheritance in Man Web site, which is a continuously updated catalog of human genes, genetic disorders, and traits, with particular focus on the molecular relationship between genetic variation and phenotype expression.

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Contributor Information and Disclosures
Author

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.

Coauthor(s)

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.

Acknowledgements

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.

References
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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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