Diffuse bronchiolitis and atelectasis as early features of primary ciliary dyskinesia in children: a genotype–phenotype study

Abstract Background Diffuse bronchiolitis and atelectasis are recognised clinical features of primary ciliary dyskinesia (PCD). This study aimed to investigate the occurrence and temporal trajectories of these features in 34 children with PCD, stratified by genotype. Methods We retrospectively reviewed children with genetically confirmed PCD at Beijing Children’s Hospital (2016–2025). Inclusion required chest computed tomography (CT) at diagnosis showing diffuse bronchiolitis alongside bronchiectasis. Atelectasis could be present or absent. Clinical and radiological trajectories were analysed in relation to genotype. Results A total of 34 children with genetically confirmed PCD (50% male) were enrolled, with pathogenic variants identified across 15 genes. Dynein-arm-associated genes (DNAH11, DNAH5, DNAI1, DNAI2) accounted for 17.65% (6/34) of cases, while the remaining 82.35% (28/34) carried mutations affecting ciliary microtubule organization and assembly. These included genes involved in axoneme ruler assembly (CCDC39, CCDC40; n = 8), radial spoke head components (RSPH4A, RSPH9; n = 6), basal body and centriole biogenesis (CCNO; n = 6), ciliary docking and assembly platform (ODAD1, ODAD3, DNAAF1, DNAAF3, OFD1; n = 6), and central pair complex defects (HYDIN; n = 2). Clinical–radiological trajectories varied by genotype. Neonatal-onset atelectasis with neonatal respiratory symptoms occurred in all patients with basal body and centriole genesis defects (100%) and in 75% of those with axoneme ruler defects. In contrast, the remaining groups showed atelectasis at a median age of 5–6.75 years, typically precipitated by pneumonia. Among 12 patients (35.29%) without atelectasis, diffuse bronchiolitis was the early radiological abnormality, with an interval from symptom onset to radiological detection of bronchiolitis ranged from 0 to 13.00 years (median 3.49 years). Bronchiectasis was present at or before definitive diagnosis in all 34 patients (100%). It was identified concurrently in 17 patients (50%) and predated diagnosis in the remaining 17 (50%). The median interval from the first radiological abnormality to bronchiectasis was 3.46 years, compared with 4.00 years to definitive diagnosis. Conclusions In paediatric PCD with ciliary microtubule organisation and assembly mutations, early features documented prior to bronchiectasis include neonatal lobar atelectasis occurring without documented alternative cause, prolonged non-resolving atelectasis after early-childhood pneumonia, and diffuse bronchiolitis with recurrent wet cough and wheezing.