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. As many as 80% of newborn babies with primary ciliary dyskinesia develop respiratory distress in the first 12-24 hours of life.^[22]

When taking a 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. Females may have a higher rate of ectopic pregnancy.

Lastly, situs inversus abnormalities on imaging are relatively specific for Kartagener syndrome.^[23]

Physical Examination

Primary ciliary dyskinesia 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.^[19]

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.^[24]

The recurrent chronic pansinusitis typically produces sinus pressure headaches in the maxillary and periorbital region. Symptoms usually improve with antibiotic therapy but have a propensity for rapid recurrence.^[24]

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.^[24]

Middle ear symptoms in primary ciliary dyskinesia (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 long-term prognosis.^[25]

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.^[15]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. Although, 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 primary ciliary dyskinesia 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.

Chest wall abnormalities, such as pectus excavatum, may be seen.

Differential Diagnoses

Kartagener M. Zur pathogenese der bronchiectasien. I Mitteilung:bronchiectasien bei situs viscerum inversus. Betr Klin Tuberk. 1933. 83:498-501.
Camner P, Mossberg B, Afzelius BA. Evidence of congenitally nonfunctioning cilia in the tracheobronchial tract in two subjects. Am Rev Respir Dis. 1975 Dec. 112(6):807-9. [QxMD MEDLINE Link].
Afzelius BA. A human syndrome caused by immotile cilia. Science. 1976 Jul 23. 193(4250):317-9. [QxMD MEDLINE Link].
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. 1977 Jul 7. 297(1):1-6. [QxMD MEDLINE Link].
Rossman CM, Forrest JB, Lee RM, Newhouse MT. The dyskinetic cilia syndrome. Ciliary motility in immotile cilia syndrome. Chest. 1980 Oct. 78(4):580-2. [QxMD MEDLINE Link].
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. 1979 Jan 11. 300(2):53-6. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Bush A, Chodhari R, Collins N, Copeland F, Hall P, Harcourt J. Primary ciliary dyskinesia: current state of the art. Arch Dis Child. 2007 Dec. 92(12):1136-40. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. 2013 Jan 10. 92(1):88-98. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
Knowles MR, Daniels LA, Davis SD, Zariwala MA, Leigh MW. Primary ciliary dyskinesia. Recent advances in diagnostics, genetics, and characterization of clinical disease. Am J Respir Crit Care Med. 2013 Oct 15. 188(8):913-22. [QxMD MEDLINE Link].
Skeik N, Jabr Fl. Kartagener syndrome. Int J Gen Med. Jan/2011. 12:41-43. [QxMD MEDLINE Link].
Marthin JK, Petersen N, Skovgaard LT, Nielsen KG. Lung function in patients with primary ciliary dyskinesia: a cross-sectional and 3-decade longitudinal study. Am J Respir Crit Care Med. 2010 Jun 1. 181(11):1262-8. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Campbell R. Managing upper respiratory tract complications of primary ciliary dyskinesia in children. Curr Opin Allergy Clin Immunol. 2012 Feb. 12(1):32-8. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Pifferi M, Bush A, Pioggia G, et al. Evaluation of pulmonary disease using static lung volumes in primary ciliary dyskinesia. Thorax. 2012 Nov. 67(11):993-9. [QxMD MEDLINE Link].
Magnin ML, Cros P, Beydon N, et al. Longitudinal lung function and structural changes in children with primary ciliary dyskinesia. Pediatr Pulmonol. 2012 Aug. 47(8):816-25. [QxMD MEDLINE Link].
Shapiro AJ, Zariwala MA, Ferkol T, Davis SD, Sagel SD, Dell SD, et al. Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD foundation consensus recommendations based on state of the art review. Pediatr Pulmonol. 2016 Feb. 51 (2):115-32. [QxMD MEDLINE Link].
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Leigh MW, O'Callaghan C, Knowles MR. The challenges of diagnosing primary ciliary dyskinesia. Proc Am Thorac Soc. 2011 Sep. 8(5):434-7. [QxMD MEDLINE Link].
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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. [QxMD MEDLINE Link].
Vali R, Ghandourah H, Charron M, Nezhad KV, Omarkhail Y, Khazaee A, et al. Evaluation of the pulmonary radioaerosol mucociliary clearance scan as an adjunctive test for the diagnosis of primary ciliary dyskinesia in children. Pediatr Pulmonol. 2019 Dec. 54 (12):2021-2027. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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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. 1992 Jan-Apr. 16(1-2):245-54. [QxMD MEDLINE Link].
Barbato A, Frischer T, Kuehni CE, Snijders D, Azevedo I, Baktai G. Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children. Eur Respir J. 2009 Dec. 34(6):1264-76. [QxMD MEDLINE Link].
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Strippoli MP, Frischer T, Barbato A, et al. Management of primary ciliary dyskinesia in European children: recommendations and clinical practice. Eur Respir J. 2012 Jun. 39(6):1482-91. [QxMD MEDLINE Link].
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Media Gallery

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.

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Table. Mutations in the Genes that Cause Human Primary Ciliary Dyskinesia^[14]

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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Author

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.

Coauthor(s)

Margo Rose Tanghetti, DO Chief Resident, Department of Otolaryngology, Oklahoma State University College of Osteopathic Medicine

Margo Rose Tanghetti, DO is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Osteopathic Colleges of Ophthalmology and Otolaryngology-Head and Neck Surgery

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; Medical Director, Pulmonary Medicine General Practice Unit (F2), Senior Staff and Attending Physician, Division of Pulmonary and Critical Care Medicine, Henry Ford Hospital

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

Disclosure: Received research grant from: Sanofi Pharmaceutical.

Chief Editor

John J Oppenheimer, MD Clinical Professor, Department of Medicine, Rutgers New Jersey Medical School; Director of Clinical Research, Pulmonary and Allergy Associates, PA

John J Oppenheimer, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, New Jersey Allergy, Asthma and Immunology Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Amgen; GSK; Aquestive; Aimmune<br/>Clinical Adjudication/Data Safety Monitoring Board for AZ, GSK, Abbvie, Sanofi; Executive Editor for Annals of Allergy, Asthma & Immunology; Editor for Medscape; Reviewer for UpToDate; Honoraria from American Board of Allergy and Immunology.

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.

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, American Society of Pediatric Otolaryngology, Society for Ear, Nose and Throat Advances in Children, Society of University Otolaryngologists-Head and Neck Surgeons, Triological Society

Disclosure: Nothing to disclose.

Arvind K Badhey, MD Clinical Assistant Professor , Attending Surgeon, Head and Neck Surgical Oncology and Microvascular Reconstructive Surgery, Department of Otolaryngology, UMass Memorial Health, University of Massuchusetts Medical School

Arvind K Badhey, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck 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.