Skip to main content Accessibility help
×
Home

The prevalence of clinical features associated with primary ciliary dyskinesia in a heterotaxy population: results of a web-based survey

  • Adam J. Shapiro (a1) (a2), Sue Tolleson-Rinehart (a2), Maimoona A. Zariwala (a3), Michael R. Knowles (a4) and Margaret W. Leigh (a2)...

Abstract

Primary ciliary dyskinesia and heterotaxy are rare but not mutually exclusive disorders, which result from cilia dysfunction. Heterotaxy occurs in at least 12.1% of primary ciliary dyskinesia patients, but the prevalence of primary ciliary dyskinesia within the heterotaxy population is unknown. We designed and distributed a web-based survey to members of an international heterotaxy organisation to determine the prevalence of respiratory features that are common in primary ciliary dyskinesia and that might suggest the possibility of primary ciliary dyskinesia. A total of 49 members (25%) responded, and 37% of the respondents have features suggesting the possibility of primary ciliary dyskinesia, defined as (1) the presence of at least two chronic respiratory symptoms, or (2) bronchiectasis or history of respiratory pathogens suggesting primary ciliary dyskinesia. Of the respondents, four completed comprehensive, in-person evaluations, with definitive primary ciliary dyskinesia confirmed in one individual, and probable primary ciliary dyskinesia identified in two others. The high prevalence of respiratory features compatible with primary ciliary dyskinesia in this heterotaxy population suggests that a subset of heterotaxy patients have dysfunction of respiratory, as well as embryonic nodal cilia. To better assess the possibility of primary ciliary dyskinesia, heterotaxy patients with chronic oto-sino-respiratory symptoms should be referred for a primary ciliary dyskinesia evaluation.

Copyright

Corresponding author

Correspondence to: Dr A. Shapiro, MD, Division of Pediatric Respirology, Montreal Children’s Hospital, 2300 Rue Tupper, D-380, Montreal, Quebec H3H 1P3, Canada. Tel: +514 412 4444; Fax: +514 412 4364; E-mail: adam.shapiro@muhc.mcgill.ca

References

Hide All
1. 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; 188: 913922.
2. Zariwala, MA, Knowles, MR, Leigh, MW. Primary ciliary dyskinesia. In: Pagon RA, Bird TC, Dolan CR, Stephens K (eds). GeneReviews. University of Washington, Seattle, WA, 2013, [updated 28 February 2013]; 159.
3. Katsuhara, K, Kawamoto, S, Wakabayashi, T, Belsky, JL. Situs inversus totalis and Kartagener’s syndrome in a Japanese population. Chest 1972; 61: 5661.
4. Torgersen, J. Situs inversus, asymmetry, and twinning. Am J Hum Genet 1950; 2: 361370.
5. Kennedy, MP, Omran, H, Leigh, MW, et al. Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia. Circulation 2007; 115: 28142821.
6. Shapiro, AJ, Davis, SD, Ferkol, T, et al. Laterality defects other than situs inversus totalis in primary ciliary dyskinesia: insights into situs ambiguus and heterotaxy. Chest 2013, in press.
7. Tanaka, Y, Okada, Y, Hirokawa, N. FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left–right determination. Nature 2005; 435: 172177.
8. Fliegauf, M, Benzing, T, Omran, H. When cilia go bad: cilia defects and ciliopathies. Nat Rev Mol Cell Biol 2007; 8: 880893.
9. Tan, SY, Rosenthal, J, Zhao, XQ, et al. Heterotaxy and complex structural heart defects in a mutant mouse model of primary ciliary dyskinesia. J Clin Invest 2007; 117: 37423752.
10. Casey, B, Cuneo, BF, Vitali, C, et al. Autosomal dominant transmission of familial laterality defects. Am J Med Genet 1996; 61: 325328.
11. Ware, SM, Peng, J, Zhu, L, et al. Identification and functional analysis of ZIC3 mutations in heterotaxy and related congenital heart defects. Am J Hum Genet 2004; 74: 93105.
12. Kaasinen, E, Aittomäki, K, Eronen, M, et al. Recessively inherited right atrial isomerism caused by mutations in growth/differentiation factor 1 (GDF1). Hum Mol Genet 2010; 19: 27472753.
13. De Luca, A, Sarkozy, A, Consoli, F, et al. Familial transposition of the great arteries caused by multiple mutations in laterality genes. Heart 2010; 96: 673677.
14. Zhu, L, Belmont, JW, Ware, SM. Genetics of human heterotaxias. Eur J Hum Genet 2006; 14: 1725.
15. Brueckner, M. Heterotaxia, congenital heart disease, and primary ciliary dyskinesia. Circulation 2007; 115: 27932795.
16. Swisher, M, Jonas, R, Tian, X, et al. Increased postoperative and respiratory complications in patients with congenital heart disease associated with heterotaxy. J Thorac Cardiovasc Surg 2011; 141: 637644.
17. Mullowney, T, Dell, S, Manson, D, Shah, V. Chest X-ray findings distinguish PCD from other causes of term neonatal respiratory distress. Am J Respir Crit Care Med 2013; 187: A2088. (Accessed 1 Jul 2013).
18. Shapiro, A, Chawla, K, Baker, B, et al. Clinical symptoms associated with primary ciliary dyskinesia, results of a multi-center study. Am J Respir Crit Care Med 2010; 181: A6728. (Abstract issue).
19. Shapiro, A, Chawla, K, Knowles, M, et al. 2009, Primary ciliary dyskinesia in children with cardiac laterality defects, including heterotaxy. Pediatric Academic Societies’ Conference, A4520.4, (Abstract). Retrieved April 1, 2013, from http://www.abstracts2view.com/pasall/view.php?nu=PAS09L1_2671.
20. Shapiro, A, Chawla, K, Baker, B, et al. Nasal nitric oxide and clinical characteristics of patients with heterotaxy: comparison to primary ciliary dyskinesia. Am J Respir Crit Care Med 2011; 183: A1209. (Abstract).
21. Leigh, MW, O'Callaghan, C, Knowles, MR. The challenges of diagnosing primary ciliary dyskinesia. Proc Am Thorac Soc 2011; 8: 434437.
22. Leigh, MW, Hazucha, MJ, Chawla, KK, et al. Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia. Ann Am Thorac Soc 2013; 10: 574581.
23. Noone, PG, Leigh, MW, Sannuti, A, et al. Primary ciliary dyskinesia: diagnostic and phenotypic features. Am J Respir Crit Care Med 2004; 169: 459467.
24. Mateos-Corral, D, Coombs, R, Grasemann, H, et al. Diagnostic value of nasal nitric oxide measured with non-velum closure techniques for children with primary ciliary dyskinesia. J Pediatr 2011; 159: 420424.
25. Chawla, KK, Shapiro, A, Hazucha, MJ, et al. Nasal nitric oxide during tidal breathing in children under 6 years of age. Am J Respir Crit Care Med 2009; 179: A3673.
26. Olbrich, H, Haffner, K, Kispert, A, et al. Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetry. Nat Genet 2002; 30: 143144.
27. 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 2006; 174: 120126.
28. Treggiari, MM, Rosenfeld, M, Mayer-Hamblett, N, et al. Early anti-pseudomonal acquisition in young patients with cystic fibrosis: rationale and design of the EPIC clinical trial and observational study. Contemp Clin Trials 2009; 30: 256268; Epub 2009 15 January.
29. Kennedy, MP, Noone, PG, Leigh, MW, et al. High-resolution CT of patients with primary ciliary dyskinesia. Am J Roentgenol 2007; 188: 12321238.
30. Counil, F, Ichay, L, Guillaumont, S, et al. Association of severe bronchial disease (bronchial casts, bronchiectasis) and partial abnormal pulmonary venous drainage in 2 children with Turner’s syndrome. Arch Pediatr 1999; 6: 10701074.
31. Bouros, D, Pare, P, Panagou, P, et al. The varied manifestation of pulmonary artery agenesis in adulthood. Chest 1995; 108: 670676.
32. Nagel, BH, Williams, H, Stewart, L, et al. Splenic state in surviving patients with visceral heterotaxy. Cardiol Young 2005; 15: 469473.
33. Øyen, N, Poulsen, G, Boyd, HA, Wohlfahrt, J, Jensen, PK, Melbye, M. Recurrence of congenital heart defects in families. Circulation 2009; 120: 295301.
34. Evans, WN. Thoracoabdominal situs: a practical approach accompanied by a short history of descriptive terms. Pediatr Cardiol 2010; 31: 10491051.

Keywords

Type Description Title
WORD
Supplementary materials

Shapiro Supplementary Material
Supplementary Material

 Word (64 KB)
64 KB

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed