Ciliary beat pattern is associated with specific ultrastructural defects in primary ciliary dyskinesia

Mark A Chilvers, Andrew Rutman, Christopher O'Callaghan, Mark A Chilvers, Andrew Rutman, Christopher O'Callaghan

Abstract

Background: The main symptoms of primary ciliary dyskinesia (PCD) are nasal rhinorrhea or blockage and moist-sounding cough. Diagnosis can be difficult and is based on an abnormal ciliary beat frequency, accompanied by specific abnormalities of the ciliary axoneme. It is unknown whether determining ciliary beat pattern related to specific ultrastructural ciliary defects might help in the diagnosis of PCD.

Objective: We sought to determine ciliary beat pattern and beat frequency (CBF) associated with the 5 common ultrastructural defects responsible for PCD.

Methods: Nasal brushings were performed on 56 children with PCD. Ciliary movement was recorded using digital high-speed video imaging to assess beat frequency and pattern. Electron microscopy was performed.

Results: In patients with an isolated outer dynein arm or with an outer and inner dynein arm defect, 55% and 80% of cilia were immotile, respectively. Cilia that moved were only flickering. Mean CBF (+/- 95% CI) was 2.3 Hz (+/- 1.2) and 0.8 Hz(+/- 0.8), respectively. Cilia with an isolated inner dynein arm or a radial spoke defect had similar beat patterns. Cilia appeared stiff, had a reduced amplitude, and failed to bend along their length. Immotile cilia were present in 10% of cilia with an inner dynein arm defect and in 30% of radial spoke defects. Mean CBF was 9.3 Hz (+/- 2.6) and 6.0 Hz (+/- 3.1), respectively. The ciliary transposition defect produced a large circular beat pattern (mean CBF, 10.7 Hz [+/- 1.1]). No cilia were immotile.

Conclusions: Different ultrastructural defects responsible for PCD result in predictable beat patterns. Recognition of these might help in the diagnostic evaluation of patients suspected of having PCD.

Figures

FIG 1
FIG 1
A, Diagram of the normal ciliary beat pattern. Cilia move in a planar motion with a forward power stroke and a backward recovery stroke that does not sweep to the side. B, Diagram of the dyskinetic beat pattern observed for cilia with either a combined inner and outer dynein arm defect or an isolated outer dynein arm defect. Cilia were virtually immotile, with the occasional slow, low-amplitude, stiff flickering motion. C, Diagram of the dyskinetic beat pattern observed for cilia with either an isolated inner dynein arm defect or a radial spoke defect. Cilia had a stiff planar forward-backward motion with markedly reduced amplitude. D, Diagram of the dyskinetic beat pattern observed for cilia with a transposition defect. Cilia beat in a large circular gyrating motion about the base of the cilium.
FIG 1
FIG 1
A, Diagram of the normal ciliary beat pattern. Cilia move in a planar motion with a forward power stroke and a backward recovery stroke that does not sweep to the side. B, Diagram of the dyskinetic beat pattern observed for cilia with either a combined inner and outer dynein arm defect or an isolated outer dynein arm defect. Cilia were virtually immotile, with the occasional slow, low-amplitude, stiff flickering motion. C, Diagram of the dyskinetic beat pattern observed for cilia with either an isolated inner dynein arm defect or a radial spoke defect. Cilia had a stiff planar forward-backward motion with markedly reduced amplitude. D, Diagram of the dyskinetic beat pattern observed for cilia with a transposition defect. Cilia beat in a large circular gyrating motion about the base of the cilium.
FIG 1
FIG 1
A, Diagram of the normal ciliary beat pattern. Cilia move in a planar motion with a forward power stroke and a backward recovery stroke that does not sweep to the side. B, Diagram of the dyskinetic beat pattern observed for cilia with either a combined inner and outer dynein arm defect or an isolated outer dynein arm defect. Cilia were virtually immotile, with the occasional slow, low-amplitude, stiff flickering motion. C, Diagram of the dyskinetic beat pattern observed for cilia with either an isolated inner dynein arm defect or a radial spoke defect. Cilia had a stiff planar forward-backward motion with markedly reduced amplitude. D, Diagram of the dyskinetic beat pattern observed for cilia with a transposition defect. Cilia beat in a large circular gyrating motion about the base of the cilium.
FIG 1
FIG 1
A, Diagram of the normal ciliary beat pattern. Cilia move in a planar motion with a forward power stroke and a backward recovery stroke that does not sweep to the side. B, Diagram of the dyskinetic beat pattern observed for cilia with either a combined inner and outer dynein arm defect or an isolated outer dynein arm defect. Cilia were virtually immotile, with the occasional slow, low-amplitude, stiff flickering motion. C, Diagram of the dyskinetic beat pattern observed for cilia with either an isolated inner dynein arm defect or a radial spoke defect. Cilia had a stiff planar forward-backward motion with markedly reduced amplitude. D, Diagram of the dyskinetic beat pattern observed for cilia with a transposition defect. Cilia beat in a large circular gyrating motion about the base of the cilium.
FIG 2
FIG 2
A, Electron micrograph of ciliary cross-section illustrating transposition defect. B, Electron micrograph of longitudinal section of ciliary axoneme illustrating the crossover of the peripheral microtubular doublet into the central position seen in the ciliary transposition defect.

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