Primary Ciliary Dyskinesia Workup

  • Author: Girish D Sharma, MD; Chief Editor: Michael R Bye, MD   more...
 
Updated: Mar 27, 2012
 

Laboratory Studies

Eleven genes with disease-causing mutations have been identified. These include 5 genes coding for outer dynein arm proteins (DNAI1, DNAI2, DNAH5, DNAH11, TXNDC3), 2 genes for radial spoke proteins (RSPH4A, RSPH9), and 4 genes for cytoplasmic proteins involved in dynein arm assembly (c14orf104/KTU, LRRC50) and in RPGR and OFD1.

Mutations in DNAI1 and DNAH5 have been detected in 38% of patients with primary ciliary dyskinesia. Commercial testing is available for all mutations in these 2 genes. A recently available commercial test that analyzes 11 primary ciliary dyskinesia genes is estimated to detect approximately 56% of patients with primary ciliary dyskinesia.

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Imaging Studies

  • Chest roentgenography may reveal changes due to chronic bronchitis and pneumonia. Dextrocardia, if present, is observed on chest roentgenographs. Bronchiectasis may be observed with recurrent lower respiratory infections.
  • Direct video cinematography or oscillography is used to analyze ciliary beat frequency and waveform.
  • Digital high-speed video (DHSV) imaging allows evaluation of ciliary beat pattern in 3 different planes in slow motion or frame-by-frame. Using DHSV imaging, patients with PCD can be classified into 3 distinct groups on the basis of ciliary beat pattern (see Pathophysiology).
  • Ciliary beat pattern analysis is a more sensitive and specific test for PCD with positive predictive value.[16]
  • Santamaria et al have studied structural lung disease in patients with PCD using a modified Brody composite high-resolution CT (HRCT) scoring system to evaluate the severity and distribution of lung abnormalities; they found that bronchiectasis, peribronchial thickening, and peripheral mucous plugging were the most common changes, followed by central mucus plugging and parenchymal abnormalities.[17]
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Other Tests

  • Mucociliary clearance studies measure the perception of sweetness after saccharin is placed on the anterior portion of the inferior turbinate. A delayed or absent response suggests impaired mucociliary clearance.
  • Nasal nitric oxide measurements have been tried to screen children with PCD.[18, 19] Extremely low levels of nitric oxide (less than 100 nL/min) may be suggestive.[20]
  • Pulmonary function testing has shown reduced values for FEV1.[7, 21] Longitudinal studies have shown a high degree of variation in the course of lung function after diagnosis that was not related to either age or lung function level at the time of diagnosis.[21]
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Procedures

Bronchoscopy reveals mucosal inflammation and mucopurulent secretions. It can also be used to confirm the reversal of bronchial anatomy in those patients with situs inversus.

Examination of the ciliary ultrastructure by electron microscopy in a nasal or bronchial ciliary biopsy sample can be used as a diagnostic test.

Nasal biopsy (brush or curettage) samples are obtained from inferior surface of turbinates. Electron microscopy reveals the abnormalities in the cilia.

Bronchial brush biopsy demonstrates ciliary ultrastructure abnormalities using an electron microscope. Due to the varying orientation of the cilia in a biopsy specimen and resultant technical difficulties in the full analysis of cilila, a quantitative method includes assessing axonemal defects in less than perfectly oriented cilia, with dynein arms being assessed only in those cilia in which these small structures can be discerned.

A review of quantitative transmission electron microscopy in 1182 patients referred for ciliary structure analysis reported confirmation of diagnosis of PCD in 242 (20%) cases.[22] In addition to describing an algorithm including screening tests such as exhaled nasal nitric oxide, saccharine test, light microscopy, and electron microscopy, the authors describe the use of transmission electron microscopy using a rapid quantitative method. However, electron microscopy does not always exclude the diagnosis of PCD.

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Contributor Information and Disclosures
Author

Girish D Sharma, MD  Professor of Pediatrics, Rush Medical College; Senior Attending, Department of Pediatrics, Director, Section of Pediatric Pulmonology and Rush Cystic Fibrosis Center, Rush University Medical Center

Girish D Sharma, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society, and Royal College of Physicians of Ireland

Disclosure: Nothing to disclose.

Specialty Editor Board

Susanna A McColley, MD  Professor of Pediatrics, Northwestern University, The Feinberg School of Medicine; Director of Cystic Fibrosis Center, Head, Division of Pulmonary Medicine, Children's Memorial Medical Center of Chicago

Susanna A McColley, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Sleep Disorders Association, and American Thoracic Society

Disclosure: Genentech Honoraria Speaking and teaching; Genentech Honoraria Consulting; Boston Scientific Consulting fee Consulting; Gilead Honoraria Speaking and teaching; Caremark Consulting fee Consulting; Vertex Pharmaceuticals Honoraria Speaking and teaching

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Heidi Connolly, MD  Associate Professor of Pediatrics and Psychiatry, University of Rochester School of Medicine and Dentistry; Director, Pediatric Sleep Medicine Services, Strong Sleep Disorders Center

Heidi Connolly, MD is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Mary E Cataletto, MD  Director of Children's Sleep Services, Winthrop Sleep Disorders Center; Professor of Clinical Pediatrics, State University of New York at Stony Brook

Mary E Cataletto, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Chest Physicians

Disclosure: Shering Plough Pharmaceuticals Honoraria Consulting

Chief Editor

Michael R Bye, MD  Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College of Physicians and Surgeons; Attending Physician, Pediatric Pulmonary Medicine, Morgan Stanley Children's Hospital of New York Presbyterian, Columbia University Medical Center

Michael R Bye, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

References

  1. Kartagener M. Zur pathogene der bronkiectasein:bronkiectasein bei situs viscerum inversus. Beitr Klin Tuberk. 1933;82:489.

  2. Kartagner M. Zur pathogenese der bronkiectasein. I Mittelung: Bronkiectasein bei situs viscerum invesus. Beitr Klin Tuberk. 1933;83:498-501.

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

  4. Carson JL, Collier AM, Hu SS. Acquired ciliary defects in nasal epithelium of children with acute viral upper respiratory infections. N Engl J Med. Feb 21 1985;312(8):463-8. [Medline].

  5. Pedersen M. Ciliary activity and pollution. Lung. 1990;168 Suppl:368-76. [Medline].

  6. Leigh MW, Pittman JE, Carson JL, Ferkol TW, Dell SD, Davis SD. Clinical and genetic aspects of primary ciliary dyskinesia/Kartagener syndrome. Genet Med. Jul 2009;11(7):473-87. [Medline].

  7. Lie H, Zariwala MA, Helms C, Bowcock AM, Carson JL, Brown DE 3rd. Primary ciliary dyskinesia in Amish communities. J Pediatr. Jun 2010;156(6):1023-5. [Medline].

  8. Sturgess JM, Chao J, Turner JA. Transposition of ciliary microtubules: another cause of impaired ciliary motility. N Engl J Med. Aug 7 1980;303(6):318-22. [Medline].

  9. Chilvers MA, Rutman A, O'Callaghan C. Ciliary beat pattern is associated with specific ultrastructural defects in primary ciliary dyskinesia. J Allergy Clin Immunol. Sep 2003;112(3):518-24. [Medline].

  10. Kuehni CE, Frischer T, Strippoli MP, Maurer E, Bush A, Nielsen KG, et al. Factors influencing age at diagnosis of primary ciliary dyskinesia in European children. Eur Respir J. Dec 2010;36(6):1248-58. [Medline].

  11. Afzelius BA, Eliasson R. Male and female infertility problems in the immotile-cilia syndrome. Eur J Respir Dis Suppl. 1983;127:144-7. [Medline].

  12. Pennarun G, Escudier E, Chapelin C, et al. Loss-of-function mutations in a human gene related to Chlamydomonas reinhardtii dynein IC78 result in primary ciliary dyskinesia. Am J Hum Genet. Dec 1999;65(6):1508-19. [Medline].

  13. Guichard C, Harricane MC, Lafitte JJ, et al. Axonemal dynein intermediate-chain gene (DNAI1) mutations result in situs inversus and primary ciliary dyskinesia (Kartagener syndrome). Am J Hum Genet. Apr 2001;68(4):1030-5. [Medline].

  14. Hornef N, Olbrich H, Horvath J, et al. DNAH5 mutations are a common cause of primary ciliary dyskinesia with outer dynein arm defects. Am J Respir Crit Care Med. Jul 15 2006;174(2):120-6. [Medline].

  15. Bush A, Ferkol T. Movement: the emerging genetics of primary ciliary dyskinesia. Am J Respir Crit Care Med. Jul 15 2006;174(2):109-10. [Medline].

  16. 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 15 2010;181(4):307-14. [Medline].

  17. Santamaria F, Montella S, Tiddens HA, et al. Structural and functional lung disease in primary ciliary dyskinesia. Chest. Aug 2008;134(2):351-7. [Medline].

  18. 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].

  19. Karadag B, James AJ, Gultekin E, Wilson NM, Bush A. Nasal and lower airway level of nitric oxide in children with primary ciliary dyskinesia. Eur Respir J. Jun 1999;13(6):1402-5. [Medline].

  20. Noone PG, Leigh MW, Sannuti A, et al. Primary ciliary dyskinesia: diagnostic and phenotypic features. Am J Respir Crit Care Med. Feb 15 2004;169(4):459-67. [Medline].

  21. 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. Jun 1 2010;181(11):1262-8. [Medline].

  22. Shoemark A, Dixon M, Corrin B, Dewar A. Twenty-year review of quantitative transmission electron microscopy for the diagnosis of primary ciliary dyskinesia. J Clin Pathol. Mar 2012;65(3):267-71. [Medline].

  23. 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. Dec 2009;34(6):1264-76. [Medline].

 
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Diagram showing the cross-section of normal cilia showing its ultrastructure. Important components are labeled.
Ciliary ultrastructure, Left, Normal cilium from a healthy individual in which both inner and outer dynein arms can clearly identified. Right, the absence of outer and inner dynein arms in a patient with primary ciliary dyskinesia. Image courtesy of J. Carson, PhD, University of North Carolina.
 
 
 
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