Ciliary and epithelial abnormalities are features of primary ciliopathies

Abstract

Background: A ciliopathy is a genetic disorder of non-motile cilia. Although over one hundred ciliopathies exist they are rare. Respiratory problems in ciliopathies have been noted but little is known of the involvement of the ciliated respiratory epithelium. Aims: To review the structure and function of motile cilia in patients with Bardet Beidl (BB), Alstroms (AS) and Sensenbrenners (SBS) syndromes referred to our national PCD diagnostic service because of respiratory symptoms. Methods: Nasal brush biopsies were taken from 5 BBS, 6 AS and 1SBS. The cilia were recorded using high speed video. TEM was used to visualise the epithelial and ciliary ultrastructure. The recordings were replayed at reduced rate for determination of ciliary beat frequency (CBF) and pattern. Ciliated cell culture was done and tests were repeated. Results: The respiratory epithelial cilia of all patients were motile with CBF ranging from 7 to 15Hz. Epithelial abnormalities included extremely dense microvilli, cystic ciliary tips , swollen cilia membranes along the shaft and microtubular disarrangement. Racket shaped microvilli and very long motile flagella were seen. These were not seen in epithelial samples from patients with a wide spectrum of other respiratory diseases. Conclusion: Patients with primary ciliopathies presenting with chronic respiratory problems may have specific epithelial and ciliary abnormalities. The significance of these findings remains unclear.