The association of neonatal respiratory distress with ciliary
ultrastructure and genotype in primary ciliary dyskinesia
Abstract
Objective: To evaluate the relationship between ciliary
ultrastructure/genotype and prevalence of neonatal respiratory distress
in primary ciliary dyskinesia (PCD). Study Design: This was a
retrospective analysis from a multicenter, prospective study of children
and adults with PCD. Participants were classified by ultrastructural
defect associated with their diagnostic genetic variants: 1) outer
dynein arm defect alone (ODA), 2) outer plus inner dynein arm defect
(ODA/IDA), 3) inner dynein arm defect with microtubular disorganization
(IDA/MTD), 4) DNAH11 (encodes ODA protein but has normal
ultrastructure), and 5) normal/near normal/other. The likelihood of
neonatal respiratory distress between ultrastructure groups or genotypes
was evaluated by multivariate analysis using logistic regression,
controlled for age, gender, race, and variant type. Similar analysis was
performed within individual genotypes to assess association of neonatal
respiratory distress with the presence of 2 loss-of-function variants.
Results: Of the 455 participants analyzed, 305 (67.0%)
reported neonatal respiratory distress. The odds ratio for neonatal
respiratory distress in the DNAH11 group was significantly lower
(OR 0.35, 95% CI 0.16-0.76) compared to neonatal respiratory distress
in the ODA group. Within the DNAH5 group, those with 2
loss-of-function variants were more likely to have neonatal respiratory
distress compared to those with possible residual function variants (OR
3.06, 95% CI 1.33-7). Conclusion: Neonatal respiratory
distress is less common in those with DNAH11 variants, thus a
high index of suspicion should remain for PCD in the absence of neonatal
respiratory distress.