Primary ciliary dyskinesia (PCD) is characterized by dysfunction of ciliary motility, which leads to ineffective mucociliary clearance and laterality defects, including heterotaxy (HTX), as motile nodal cilia determine left?right asymmetry during embryonic development.

This study aimed to identify ciliary defects linked to HTX but not PCD due to a lack of a typical respiratory phenotype.

A retrospective observational study was conducted at the Royal Brompton Hospital, London, UK. 43 HTX patients not diagnosed with PCD by ERS criteria and 9 controls were included. Videos of cilia motility were analyzed using in-house software, and cilia ultrastructure was assessed by transmission electron microscopy (TEM).

Non-PCD HTX patients (0-14 years) had a mean ciliary beat frequency within a normal range (10.12 Hz; SD 2.13). However, the main ciliary beat pattern was abnormal in 32.6%, with reduced amplitude (16.3%), stiff (7%), or mixed (9.3%) beat pattern. Reviewing the TEM data, 20.8% of HTX patients had >5% of cilia with an axonemal disorganization defect (cutoff based on 4.57% mean of controls). These HTX patients with a TEM defect had a significantly increased beat amplitude/second compared to those without a TEM defect and controls (73.6 vs 53.8 and 50.5 µm/s, p-value 0.0012, Kruskal-Wallis test).

This study shows abnormal ciliary beat and ultrastructural defects in a proportion of HTX patients who lack a typical PCD phenotype. These abnormalities may impact the nodal cilia and determination of organ laterality but have a mild effect on respiratory cilia.

We acknowledge the support of the ERS STR Fellowship 2023, and this work is a collaboration with BEAT-PCD.