Clinical features of childhood primary ciliary dyskinesia by genotype and ultrastructural phenotype

Stephanie Davis, Thomas W. Ferkol, Margaret Rosenfeld, Hye Seung Lee, Sharon D. Dell, Scott D. Sagel, Carlos Milla, Maimoona A. Zariwala, Jessica E. Pittman, Adam J. Shapiro, Johnny L. Carson, Jeffrey P. Krischer, Milan J. Hazucha, Matthew L. Cooper, Michael R. Knowles, Margaret W. Leigh

Research output: Contribution to journalArticle

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Abstract

Rationale: The relationship between clinical phenotype of childhood primary ciliary dyskinesia (PCD) and ultrastructural defects and genotype is poorly defined. Objectives: To delineate clinical features of childhood PCD and their associations with ultrastructural defects and genotype. Methods: A total of 118 participants younger than 19 years old with PCD were evaluated prospectively at six centers in North America using standardized procedures for diagnostic testing, spirometry, chest computed tomography, respiratory cultures, and clinical phenotyping. Measurements and Main Results: Clinical features included neonatal respiratory distress (82%), chronic cough (99%), and chronic nasal congestion (97%). There were no differences in clinical features or respiratory pathogens in subjects with outer dynein arm (ODA) defects (ODA alone; n = 54) and ODA plus inner dynein arm (IDA) defects (ODA 1 IDA; n = 18) versus subjects with IDA and central apparatus defects with microtubular disorganization (IDA/ CA/MTD; n = 40). Median FEV 1 was worse in the IDA/CA/MTD group (72% predicted) versus the combined ODA groups (92% predicted; P = 0.003). Median body mass index was lower in the IDA/ CA/MTD group (46th percentile) versus the ODA groups (70th percentile; P = 0.003). For all 118 subjects, median number of lobes with bronchiectasis was three and alveolar consolidation was two. However, the 5- to 11-year-old IDA/CA/MTD group had more lobes of bronchiectasis (median, 5; P = 0.0008) and consolidation (median, 3; P = 0.0001) compared with the ODA groups (median, 3 and 2, respectively). Similar findings were observed when limited to participants with biallelic mutations. Conclusions: Lung disease was heterogeneous across all ultrastructural and genotype groups, but worse in those with IDA/ CA/MTD ultrastructural defects, most of whom had biallelic mutations in CCDC39 or CCDC40.

Original languageEnglish
Pages (from-to)316-324
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume191
Issue number3
DOIs
StatePublished - Feb 1 2015

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Kartagener Syndrome
Dyneins
Arm
Genotype
Phenotype
Bronchiectasis
Mutation
Spirometry

Keywords

  • Cilia
  • Kartagener syndrome
  • Respiratory function tests
  • Ultrastructure
  • X-ray computed tomography scanners

ASJC Scopus subject areas

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

Cite this

Clinical features of childhood primary ciliary dyskinesia by genotype and ultrastructural phenotype. / Davis, Stephanie; Ferkol, Thomas W.; Rosenfeld, Margaret; Lee, Hye Seung; Dell, Sharon D.; Sagel, Scott D.; Milla, Carlos; Zariwala, Maimoona A.; Pittman, Jessica E.; Shapiro, Adam J.; Carson, Johnny L.; Krischer, Jeffrey P.; Hazucha, Milan J.; Cooper, Matthew L.; Knowles, Michael R.; Leigh, Margaret W.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 191, No. 3, 01.02.2015, p. 316-324.

Research output: Contribution to journalArticle

Davis, S, Ferkol, TW, Rosenfeld, M, Lee, HS, Dell, SD, Sagel, SD, Milla, C, Zariwala, MA, Pittman, JE, Shapiro, AJ, Carson, JL, Krischer, JP, Hazucha, MJ, Cooper, ML, Knowles, MR & Leigh, MW 2015, 'Clinical features of childhood primary ciliary dyskinesia by genotype and ultrastructural phenotype', American Journal of Respiratory and Critical Care Medicine, vol. 191, no. 3, pp. 316-324. https://doi.org/10.1164/rccm.201409-1672OC
Davis, Stephanie ; Ferkol, Thomas W. ; Rosenfeld, Margaret ; Lee, Hye Seung ; Dell, Sharon D. ; Sagel, Scott D. ; Milla, Carlos ; Zariwala, Maimoona A. ; Pittman, Jessica E. ; Shapiro, Adam J. ; Carson, Johnny L. ; Krischer, Jeffrey P. ; Hazucha, Milan J. ; Cooper, Matthew L. ; Knowles, Michael R. ; Leigh, Margaret W. / Clinical features of childhood primary ciliary dyskinesia by genotype and ultrastructural phenotype. In: American Journal of Respiratory and Critical Care Medicine. 2015 ; Vol. 191, No. 3. pp. 316-324.
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AU - Dell, Sharon D.

AU - Sagel, Scott D.

AU - Milla, Carlos

AU - Zariwala, Maimoona A.

AU - Pittman, Jessica E.

AU - Shapiro, Adam J.

AU - Carson, Johnny L.

AU - Krischer, Jeffrey P.

AU - Hazucha, Milan J.

AU - Cooper, Matthew L.

AU - Knowles, Michael R.

AU - Leigh, Margaret W.

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N2 - Rationale: The relationship between clinical phenotype of childhood primary ciliary dyskinesia (PCD) and ultrastructural defects and genotype is poorly defined. Objectives: To delineate clinical features of childhood PCD and their associations with ultrastructural defects and genotype. Methods: A total of 118 participants younger than 19 years old with PCD were evaluated prospectively at six centers in North America using standardized procedures for diagnostic testing, spirometry, chest computed tomography, respiratory cultures, and clinical phenotyping. Measurements and Main Results: Clinical features included neonatal respiratory distress (82%), chronic cough (99%), and chronic nasal congestion (97%). There were no differences in clinical features or respiratory pathogens in subjects with outer dynein arm (ODA) defects (ODA alone; n = 54) and ODA plus inner dynein arm (IDA) defects (ODA 1 IDA; n = 18) versus subjects with IDA and central apparatus defects with microtubular disorganization (IDA/ CA/MTD; n = 40). Median FEV 1 was worse in the IDA/CA/MTD group (72% predicted) versus the combined ODA groups (92% predicted; P = 0.003). Median body mass index was lower in the IDA/ CA/MTD group (46th percentile) versus the ODA groups (70th percentile; P = 0.003). For all 118 subjects, median number of lobes with bronchiectasis was three and alveolar consolidation was two. However, the 5- to 11-year-old IDA/CA/MTD group had more lobes of bronchiectasis (median, 5; P = 0.0008) and consolidation (median, 3; P = 0.0001) compared with the ODA groups (median, 3 and 2, respectively). Similar findings were observed when limited to participants with biallelic mutations. Conclusions: Lung disease was heterogeneous across all ultrastructural and genotype groups, but worse in those with IDA/ CA/MTD ultrastructural defects, most of whom had biallelic mutations in CCDC39 or CCDC40.

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KW - Cilia

KW - Kartagener syndrome

KW - Respiratory function tests

KW - Ultrastructure

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