title: Clinical features of childhood primary ciliary dyskinesia by genotype and ultrastructural phenotype.
abstract: BACKGROUND
  The relationship between clinical phenotype of childhood primary ciliary dyskinesia (PCD) and ultrastructural defects and genotype is poorly defined.
  
  
  OBJECTIVE
  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.
  
  
  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 + IDA; n = 18) versus subjects with IDA and central apparatus defects with microtubular disorganization (IDA/CA/MTD; n = 40). Median FEV1 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.
authors.affiliation: 1 Department of Pediatrics and.
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Davis
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Ferkol
authors.forename: Margaret
authors.initials: M
authors.lastname: Rosenfeld
authors.forename: Hye-Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Dell
authors.forename: Scott D
authors.initials: SD
authors.lastname: Sagel
authors.forename: Carlos
authors.initials: C
authors.lastname: Milla
authors.forename: Maimoona A
authors.initials: MA
authors.lastname: Zariwala
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Pittman
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Shapiro
authors.forename: Johnny L
authors.initials: JL
authors.lastname: Carson
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Krischer
authors.forename: Milan J
authors.initials: MJ
authors.lastname: Hazucha
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Cooper
authors.forename: Michael R
authors.initials: MR
authors.lastname: Knowles
authors.forename: Margaret W
authors.initials: MW
authors.lastname: Leigh
mesh_terms: D000293:Adolescent; D000483:Alleles; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D015992:Body Mass Index; D002170:Canada; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007619:Kartagener Syndrome / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D010641:Phenotype; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics*; D012720:Severity of Illness Index; D013147:Spirometry; D014481:United States
chemical_list: D015415:Biomarkers; C556026:CCDC39 protein, human; C556028:CCDC40 protein, human; D003598:Cytoskeletal Proteins; D011506:Proteins
keywords: Kartagener syndrome; X-ray computed tomography scanners; cilia; respiratory function tests; ultrastructure