Identification of distinct ciliary beat pattern abnormalities by high-speed video microscopy in primary ciliary dyskinesia

Abstract

Introduction: Primary Ciliary Dyskinesia (PCD) is a rare, genetically heterogenous disorder leading to recurrent respiratory tract infections due to abnormal ciliary motility causing impaired mucociliary clearance. High-speed videomicroscopy analysis (HVMA) of ciliary beat pattern (CBP) and frequency as the current first-line diagnostic tool is an increasing challenge, because current studies widely expended the spectrum of HVMA findings from very subtle to markedly abnormal. Objectives: We assigned typical HVMA findings to genetically confirmed PCD individuals in order to identify typical patterns for various PCD variants. Methods: We assessed 1072 videos from nasal brush biopsies of 66 PCD individuals by HVMA as part of routine diagnostic work-up. HVMA findings were subsequently correlated with the genotype (biallelic mutations in 17 genes). Results: Distinct CBP correlated well with genetic findings, which allows the classification of typical HVMA findings for various genetic groups: Respiratory cilia with outer dynein arm defects (ODA) showed minimal residual movements with a minority of cilia being completely immotile. Cilia with combined inner (IDA) and ODA defects were completely immotile. Defects of the central pair apparatus resulted in a rigid and uncoordinated CBP. Combined IDA and microtubular disorganization defects resulted in a hyperkinetic, very stiff and vibratory CBP. Nexin link defects showed an almost regular CBP with only slightly reduced beating amplitude. Conclusion: This study improves clinical PCD diagnostics by classifying different PCD subtypes using HVMA as the first-line diagnostic tool and facilitates the subsequent diagnostics.