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Chest. 2014 Nov;146(5):1176-1186. doi: 10.1378/chest.13-1704.

Laterality defects other than situs inversus totalis in primary ciliary dyskinesia: insights into situs ambiguus and heterotaxy.

Author information

1
From the Department of Pediatrics, Montreal Children's Hospital, McGill University, Montreal, QC, Canada. Electronic address: adam.shapiro@muhc.mcgill.ca.
2
Department of Pediatrics, Riley Hospital for Children, Indiana University, Indianapolis, IN.
3
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
4
Department of Pediatrics, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
5
Department of Pediatrics, Seattle Children's Hospital and University of Washington, Seattle, WA.
6
National Institute of Allergy and Infectious Diseases, Bethesda, MD.
7
Department of Pediatrics, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, CO.
8
Department of Pediatrics, Stanford University, Palo Alto, CA.
9
Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC.
10
Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC.
11
Department of Pediatrics, University of North Carolina School of Medicine, on behalf of the Genetic Disorders of Mucociliary Clearance Consortium, Chapel Hill, NC.

Abstract

BACKGROUND:

Motile cilia dysfunction causes primary ciliary dyskinesia (PCD), situs inversus totalis (SI), and a spectrum of laterality defects, yet the prevalence of laterality defects other than SI in PCD has not been prospectively studied.

METHODS:

In this prospective study, participants with suspected PCD were referred to our multisite consortium. We measured nasal nitric oxide (nNO) level, examined cilia with electron microscopy, and analyzed PCD-causing gene mutations. Situs was classified as (1) situs solitus (SS), (2) SI, or (3) situs ambiguus (SA), including heterotaxy. Participants with hallmark electron microscopic defects, biallelic gene mutations, or both were considered to have classic PCD.

RESULTS:

Of 767 participants (median age, 8.1 years, range, 0.1-58 years), classic PCD was defined in 305, including 143 (46.9%), 125 (41.0%), and 37 (12.1%) with SS, SI, and SA, respectively. A spectrum of laterality defects was identified with classic PCD, including 2.6% and 2.3% with SA plus complex or simple cardiac defects, respectively; 4.6% with SA but no cardiac defect; and 2.6% with an isolated possible laterality defect. Participants with SA and classic PCD had a higher prevalence of PCD-associated respiratory symptoms vs SA control participants (year-round wet cough, P < .001; year-round nasal congestion, P = .015; neonatal respiratory distress, P = .009; digital clubbing, P = .021) and lower nNO levels (median, 12 nL/min vs 252 nL/min; P < .001).

CONCLUSIONS:

At least 12.1% of patients with classic PCD have SA and laterality defects ranging from classic heterotaxy to subtle laterality defects. Specific clinical features of PCD and low nNO levels help to identify PCD in patients with laterality defects.

TRIAL REGISTRY:

ClinicalTrials.gov; No.: NCT00323167; URL: www.clinicaltrials.gov.

PMID:
24577564
PMCID:
PMC4219335
DOI:
10.1378/chest.13-1704
[Indexed for MEDLINE]
Free PMC Article

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