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 (NRD) 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 NRD 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 NRD with the presence of 2 loss-of-function variants.

Results: Of the 455 participants analyzed, 305 (67.0%) reported NRD. The odds ratio for NRD in the DNAH11 group was significantly lower (OR: 0.35, 95% CI: 0.16-0.76) compared to NRD in the ODA group. Within the DNAH5 group, those with two loss-of-function variants were more likely to have NRD compared to those with possible residual function variants (OR: 3.06, 95% CI: 1.33-7).

Conclusion: NRD is less common in those with DNAH11 variants, thus a high index of suspicion should remain for PCD in the absence of NRD. Variant type (loss-of-function vs. residual function) may explain phenotypic variability within individual PCD genes.