Laterality defects other than situs inversus totalis in primary ciliary dyskinesia

Insights into situs ambiguus and heterotaxy

Adam J. Shapiro, Stephanie Davis, Thomas Ferkol, Sharon D. Dell, Margaret Rosenfeld, Kenneth N. Olivier, Scott D. Sagel, Carlos Milla, Maimoona A. Zariwala, Whitney Wolf, Johnny L. Carson, Milan J. Hazucha, Kimberlie Burns, Blair Robinson, Michael R. Knowles, Margaret W. Leigh

Research output: Contribution to journalArticle

66 Citations (Scopus)

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 classifi ed 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 defi ned 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. Specifi c clinical features of PCD and low nNO levels help to identify PCD in patients with laterality defects.

Original languageEnglish
Pages (from-to)1176-1186
Number of pages11
JournalChest
Volume146
Issue number5
DOIs
StatePublished - Nov 1 2014

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Heterotaxy Syndrome
Kartagener Syndrome
Situs Inversus
Nose
Nitric Oxide
Cilia
Mutation
Cough
Genes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Shapiro, A. J., Davis, S., Ferkol, T., Dell, S. D., Rosenfeld, M., Olivier, K. N., ... Leigh, M. W. (2014). Laterality defects other than situs inversus totalis in primary ciliary dyskinesia: Insights into situs ambiguus and heterotaxy. Chest, 146(5), 1176-1186. https://doi.org/10.1378/chest.13-1704

Laterality defects other than situs inversus totalis in primary ciliary dyskinesia : Insights into situs ambiguus and heterotaxy. / Shapiro, Adam J.; Davis, Stephanie; Ferkol, Thomas; Dell, Sharon D.; Rosenfeld, Margaret; Olivier, Kenneth N.; Sagel, Scott D.; Milla, Carlos; Zariwala, Maimoona A.; Wolf, Whitney; Carson, Johnny L.; Hazucha, Milan J.; Burns, Kimberlie; Robinson, Blair; Knowles, Michael R.; Leigh, Margaret W.

In: Chest, Vol. 146, No. 5, 01.11.2014, p. 1176-1186.

Research output: Contribution to journalArticle

Shapiro, AJ, Davis, S, Ferkol, T, Dell, SD, Rosenfeld, M, Olivier, KN, Sagel, SD, Milla, C, Zariwala, MA, Wolf, W, Carson, JL, Hazucha, MJ, Burns, K, Robinson, B, Knowles, MR & Leigh, MW 2014, 'Laterality defects other than situs inversus totalis in primary ciliary dyskinesia: Insights into situs ambiguus and heterotaxy', Chest, vol. 146, no. 5, pp. 1176-1186. https://doi.org/10.1378/chest.13-1704
Shapiro, Adam J. ; Davis, Stephanie ; Ferkol, Thomas ; Dell, Sharon D. ; Rosenfeld, Margaret ; Olivier, Kenneth N. ; Sagel, Scott D. ; Milla, Carlos ; Zariwala, Maimoona A. ; Wolf, Whitney ; Carson, Johnny L. ; Hazucha, Milan J. ; Burns, Kimberlie ; Robinson, Blair ; Knowles, Michael R. ; Leigh, Margaret W. / Laterality defects other than situs inversus totalis in primary ciliary dyskinesia : Insights into situs ambiguus and heterotaxy. In: Chest. 2014 ; Vol. 146, No. 5. pp. 1176-1186.
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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 classifi ed 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 defi ned 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. Specifi c clinical features of PCD and low nNO levels help to identify PCD in patients with laterality defects.",
author = "Shapiro, {Adam J.} and Stephanie Davis and Thomas Ferkol and Dell, {Sharon D.} and Margaret Rosenfeld and Olivier, {Kenneth N.} and Sagel, {Scott D.} and Carlos Milla and Zariwala, {Maimoona A.} and Whitney Wolf and Carson, {Johnny L.} and Hazucha, {Milan J.} and Kimberlie Burns and Blair Robinson and Knowles, {Michael R.} and Leigh, {Margaret W.}",
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T2 - Insights into situs ambiguus and heterotaxy

AU - Shapiro, Adam J.

AU - Davis, Stephanie

AU - Ferkol, Thomas

AU - Dell, Sharon D.

AU - Rosenfeld, Margaret

AU - Olivier, Kenneth N.

AU - Sagel, Scott D.

AU - Milla, Carlos

AU - Zariwala, Maimoona A.

AU - Wolf, Whitney

AU - Carson, Johnny L.

AU - Hazucha, Milan J.

AU - Burns, Kimberlie

AU - Robinson, Blair

AU - Knowles, Michael R.

AU - Leigh, Margaret W.

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N2 - 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 classifi ed 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 defi ned 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. Specifi c clinical features of PCD and low nNO levels help to identify PCD in patients with laterality defects.

AB - 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 classifi ed 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 defi ned 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. Specifi c clinical features of PCD and low nNO levels help to identify PCD in patients with laterality defects.

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