kartagener syndrome clinical presentation

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Kartagener Syndrome Clinical Presentation

Author: John P Bent lll, MD; Chief Editor: Zab Mosenifar, MD more...

Updated: Apr 19, 2013

History

Patients present with chronic upper and lower respiratory tract disease resulting from ineffective mucociliary

clearance. A typical presentation is that of rhinorrhea and/or mucopurulent discharge since birth. Immotile

spermatozoa result in male sterility.

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. [14]

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. [14]

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.[14]

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. [15]

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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.[16] 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.

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. [17]

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.[18]

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.[19]

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.[20]

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.[21]

Contributor Information and Disclosures Author

John P Bent lll, MD Associate Professor, Director of Medical Student Education, Departments of

Otolaryngology - Head and Neck Surgery and Pediatrics, Albert Einstein School of Medicine; Director, Airway

Clinic, Children's Hospital at Montefiore

John P Bent lll, MD is a member of the following medical societies: American Academy of Otolaryngology-Head

and Neck Surgery, American Medical Association, American Rhinologic Society, American Society of Pediatric

Otolaryngology, Society for Ear, Nose and Throat Advances in Children, and Society of University

Otolaryngologists-Head and Neck Surgeons

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

http://www.entnet.org/


http://www.suo-aado.org/SUO/index.html

http://www.sentac.org/

http://www.aspo.us/

http://www.american-rhinologic.org/

http://www.ama-assn.org/






and Neck Surgery, American Medical Student Association/Foundation, and Wilderness Medical Society


Specialty Editor Board

Ryland P Byrd Jr, MD Professor, Department of Internal Medicine, Division of Pulmonary Diseases and

Critical Care Medicine, East Tennessee State University, James H Quillen College of Medicine

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

and American Thoracic Society


Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center

College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Daniel R Ouellette, MD, FCCP Associate Professor of Medicine, Wayne State University School of Medicine;

Senior Academic Advisor, Pulmonary and Critical Care Fellowship Program, Henry Ford Hospital; Vice Chair,

Health and Science Policy Committee, American College of Chest Physicians

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


Timothy D Rice, MD Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent

Medicine, St Louis University School of Medicine

Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and

American College of Physicians


Chief Editor

Zab Mosenifar, MD Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild

Pulmonary Disease Institute, Professor and Executive Vice Chair, Department of Medicine, Cedars Sinai

Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians,

American College of Physicians, American Federation for Medical Research, and American Thoracic Society


Additional Contributors

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

1. Kartagener M. Zur pathogenese der bronchiectasien. I Mitteilung:bronchiectasien bei situs viscerum

inversus. Betr Klin Tuberk . 1933;83:498-501.

2. Camner P, Mossberg B, Afzelius BA. Evidence of congenitally nonfunctioning cilia in the tracheobronchial

tract in two subjects. Am Rev Respir Dis. Dec 1975;112(6):807-9. [Medline].

3. Afzelius BA. A human syndrome caused by immotile cilia. Science. Jul 23 1976;193(4250):317-9.


http://reference.medscape.com/medline/abstract/1081860

http://www.thoracic.org/

http://www.afmr.org/

http://www.acponline.org/

http://www.chestnet.org/

http://www.acponline.org/

http://www.aap.org/

http://www.sccm.org/





http://www.wms.org/

http://www.amsa.org/






[Medline].

4. Eliasson R, Mossberg B, Camner P, Afzelius BA. The immotile-cilia syndrome. A congenital ciliary

abnormality as an etiologic factor in chronic airway infections and male sterility. N Engl J Med . Jul 7

1977;297(1):1-6. [Medline].

5. Rossman CM, Forrest JB, Lee RM, Newhouse MT. The dyskinetic cilia syndrome. Ciliary motility in

immotile cilia syndrome. Chest . Oct 1980;78(4):580-2. [Medline].

6. Sturgess JM, Chao J, Wong J, Aspin N, Turner JA. Cilia with defective radial spokes: a cause of human

respiratory disease. N Engl J Med . Jan 11 1979;300(2):53-6. [Medline].

7. Pedersen M. Specific types of abnormal ciliary motility in Kartagener's syndrome and analogous

respiratory disorders. A quantified microphoto-oscillographic investigation of 27 patients. Eur J Respir Dis

Suppl . 1983;127:78-90. [Medline].

8. Cho DY, Hwang PH, Illek B. Characteristics of chloride transport in nasal mucosa from patients with

primary ciliary dyskinesia. Laryngoscope. July 2010;120(7):1460-1464. [Medline].

9. Pifferi M, Bush A, Caramella D, Di Cicco M, Zangani M, Chinellato I, et al. Agenesis of paranasal sinuses

and nasal nitric oxide in primary ciliary dyskinesia. Eur Respir J . March 2011;37(3):566-571. [Medline].

10. Campbell R. Managing upper respiratory tract complications of primary ciliary dyskinesia in children. Curr

Opin Allergy Clin Immunol . Feb 2012;12(1):32-8. [Medline].

11. Sommer JU, Schäfer K, Omran H, Olbrich H, Wallmeier J, Blum A, et al. ENT manifestations in patients

with primary ciliary dyskinesia: prevalence and significance of otorhinolaryngologic co-morbidities. Eur

Arch Otorhinolaryng . March 2011;268(3):383-388. [Medline].

12. Pifferi M, Bush A, Pioggia G, et al. Evaluation of pulmonary disease using static lung volumes in primary

ciliary dyskinesia. Thorax . Nov 2012;67(11):993-9. [Medline].

13. Magnin ML, Cros P, Beydon N, et al. Longitudinal lung function and structural changes in children with

primary ciliary dyskinesia. Pediatr Pulmonol . Aug 2012;47(8):816-25. [Medline].

14. Greenstone M, Stanley P, Cole P, Mackay I. Upper airway manifestations of primary ciliary dyskinesia. J

Laryngol Otol . Oct 1985;99(10):985-91. [Medline].

15. Prulière-Escabasse V, Coste A, Chauvin P, Fauroux B, Tamalet A, Garabedian EN, et al. Otologic

features in children with primary ciliary dyskinesia. Arch Otolaryngology Head and Neck Surg . Nov

2010;136(11):1121-1126. [Medline].

16. Skeik N, Jabr Fl. Kartagener syndrome. Int J Gen Med . Jan/2011;12:41-43. [Medline].

17. Bush A, Chodhari R, Collins N, Copeland F, Hall P, Harcourt J. Primary ciliary dyskinesia: current state

of the art. Arch Dis Child . Dec 2007;92(12):1136-40. [Medline].

18. Geremek M, Bruinenberg M, Ziętkiewicz E, Pogorzelski A, Witt M, Wijmenga C. Gene expression

studies in cells from primary ciliary dyskinesia patients identify 208 potential ciliary genes. Hum Genet .

March 2011;129:283-293. [Medline].

19. Becker-Heck A, Zohn IE, Okabe N, Pollock A, Lenhart KB, Sullivan-Brown J, et al. The coiled-coil domain

containing protein CCDC40 is essential for motile cilia function and left-right axis formation. Nat Genet .

Jan 2011;43(1):79-84. [Medline].

20. Onoufriadis A, Paff T, Antony D, et al. Splice-site mutations in the axonemal outer dynein arm docking

complex gene CCDC114 cause primary ciliary dyskinesia. Am J Hum Genet . Jan 10 2013;92(1):88-98.

[Medline]. [Full Text].

21. Milara J, Armengot M, Mata M, Morcillo EJ, Cortijo J. Role of adenylate kinase type 7 expression on cilia

motility: possible link in primary ciliary dyskinesia. Am J Rhinol Allergy . May 2010;24(3):181-185.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542455/























[Medline].

22. Nadel HR, Stringer DA, Levison H, Turner JA, Sturgess JM. The immotile cilia syndrome: radiological

manifestations. Radiology . Mar 1985;154(3):651-5. [Medline].

23. Pifferi M, Bush A, Maggi F, Michelucci A, Ricci V, Conidi ME, et al. Nasal nitric oxide and nitric oxide

synthase expression in primary ciliary dyskinesia. Eur Respir J . March 2011;37:572-577. [Medline].

24. Stannard WA, Chilvers MA, Rutman AR, Williams CD, O'Callaghan C. Diagnostic testing of patients

suspected of primary ciliary dyskinesia. Am J Respir Crit Care Med . Feb 2010;181(4):307-314. [Medline].

25. Kupferberg SB, Bent JP, Porubsky ES. The evaluation of ciliary function: electron versus light

microscopy. Am J Rhinol . May-Jun 1998;12(3):199-201. [Medline].

26. Mierau GW, Agostini R, Beals TF, Carlén B, Dardick I, Henderson DW, et al. The role of electron

microscopy in evaluating ciliary dysfunction: report of a workshop. Ultrastruct Pathol . Jan-Apr 1992;16(1-

2):245-54. [Medline].

27. Desai M, Weller PH, Spencer DA. Clinical benefit from nebulized human recombinant DNase in

Kartagener's syndrome. Pediatr Pulmonol . Nov 1995;20(5):307-8. [Medline].

28. Strippoli MP, Frischer T, Barbato A, et al. Management of primary ciliary dyskinesia in European children:

recommendations and clinical practice. Eur Respir J . Jun 2012;39(6):1482-91. [Medline].

29. Parsons DS, Greene BA. A treatment for primary ciliary dyskinesia: efficacy of functional endoscopic

sinus surgery. Laryngoscope. Nov 1993;103(11 Pt 1):1269-72. [Medline].

30. Afzelius BA, Gargani G, Romano C. Abnormal length of cil ia as a possible cause of defective mucociliary

clearance. Eur J Respir Dis. Mar 1985;66(3):173-80. [Medline].

31. Bent JP 3rd, Smith RJ. Intraoperative diagnosis of primary ciliary dyskinesia. Otolaryngol Head Neck

Surg . Jan 1997;116(1):64-7. [Medline].

32. Carlén B, Stenram U. Ultrastructural diagnosis in the immotile cilia syndrome. Ultrastruct Pathol .

1987;11(5-6):653-8. [Medline].

33. Chin GY, Karas DE, Kashgarian M. Correlation of presentation and pathologic condition in primary ciliarydyskinesia. Arch Otolaryngol Head Neck Surg . Nov 2002;128(11):1292-4. [Medline].

34. Corbelli R, Bringolf-Isler B, Amacher A, Sasse B, Spycher M, Hammer J. Nasal nitric oxide

measurements to screen children for primary ciliary dyskinesia. Chest . Oct 2004;126(4):1054-9.

[Medline].

35. de Iongh RU, Rutland J. Ciliary defects in healthy subjects, bronchiectasis, and primary ciliary

dyskinesia. Am J Respir Crit Care Med . May 1995;151(5):1559-67. [Medline].

36. Eavey RD, Nadol JB Jr, Holmes LB, Laird NM, Lapey A, Joseph MP, et al. Kartagener's syndrome. A

blinded, controlled study of cilia ultrastructure. Arch Otolaryngol Head Neck Surg . Jun 1986;112(6):646-

50. [Medline].

37. el-Sayed Y, al-Sarhani A, al-Essa AR. Otological manifestations of primary ciliary dyskinesia. Clin

Otolaryngol Allied Sci . Jun 1997;22(3):266-70. [Medline].

38. Engesaeth VG, Warner JO, Bush A. New associations of primary ciliary dyskinesia syndrome. Pediatr

Pulmonol . Jul 1993;16(1):9-12. [Medline].

39. Fonzi L, Lungarella G, Palatresi R. Lack of kinocilia in the nasal mucosa in the immotile-cilia syndrome.

Eur J Respir Dis. Nov 1982;63(6):558-63. [Medline].

40. Lungarella G, De Santi MM, Palatresi R, Tosi P. Ultrastructural observations on basal apparatus of

respiratory cilia in immotile cilia syndrome. Eur J Respir Dis. Mar 1985;66(3):165-72. [Medline].

























Medscape Reference © 2011 WebMD, LLC

41. Lurie M, Rennert G, Goldenberg S, Rivlin J, Greenberg E, Katz I. Ciliary ultrastructure in primary ciliary

dyskinesia and other chronic respiratory conditions: the relevance of microtubular abnormalities.

Ultrastruct Pathol . Sep-Oct 1992;16(5):547-53. [Medline].

42. Merveille AC, Davis EE, Becker-Heck A, Legendre M, Amirav I, Bataille G, et al. CCDC39 is required for

assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in

humans and dogs. Nat Genet . Jan 2011;43(1):72-78. [Medline].

43. Mygind N, Pedersen M. Nose-, sinus- and ear-symptoms in 27 patients with primary ciliary dyskinesia.

Eur J Respir Dis Suppl . 1983;127:96-101. [Medline].

44. Noone PG, Leigh MW, Sannuti A, Minnix SL, Carson JL, Hazucha M, et al. Primary ciliary dyskinesia:

diagnostic and phenotypic features. Am J Respir Crit Care Med . Feb 15 2004;169(4):459-67. [Medline].

45. Philpott CM, McKiernan DC. Bronchiectasis and sino-nasal disease: a review. J Laryngol Otol . Jan

2008;122(1):11-5. [Medline].

46. Rayner CF, Rutman A, Dewar A, Greenstone MA, Cole PJ, Wilson R. Ciliary disorientation alone as a

cause of primary ciliary dyskinesia syndrome. Am J Respir Crit Care Med . Mar 1996;153(3):1123-9.

[Medline].

47. Schidlow DV. Primary ciliary dyskinesia (the immotile cilia syndrome). Ann Allergy . Dec 1994;73(6):457-

68; quiz 468-70. [Medline].

48. Sleigh MA, Blake JR, Liron N. The propulsion of mucus by cilia. Am Rev Respir Dis. Mar

1988;137(3):726-41. [Medline].

49. Teknos TN, Metson R, Chasse T, Balercia G, Dickersin GR. New developments in the diagnosis of

Kartagener's syndrome. Otolaryngol Head Neck Surg . Jan 1997;116(1):68-74. [Medline].

50. van der Baan S, Veerman AJ, Bezemer PD, Feenstra L. Primary ciliary dyskinesia: quantitative

investigation of the ciliary ultrastructure with statistical analysis. Ann Otol Rhinol Laryngol . May-Jun

1987;96(3 Pt 1):264-72. [Medline].

51. van der Baan S, Veerman AJ, Wulffraat N, Bezemer PD, Feenstra L. Primary ciliary dyskinesia: ciliary

activity. Acta Otolaryngol . Sep-Oct 1986;102(3-4):274-81. [Medline].












kartagener syndrome clinical presentation

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