Phenotypic features of ciliary dyskinesia among patients with congenital cardiovascular malformations

Abstract

Background Cilia are cell membrane‐bound organelles responsible for airway mucus clearance, establishment of left‐right organ asymmetry, cardiogenesis, and many other functions in utero. Phenotypic features suggestive of respiratory ciliary dyskinesia among patients with heterotaxy syndrome, defined as complex cardiovascular malformations (CVM) and situs ambiguus (SA), has not been adequately explored. Objectives We hypothesized that there is a greater incidence of phenotypic features consistent with ciliary dyskinesia among patients with heterotaxy syndrome compared to patients with other CVM and laterality defects without heterotaxy syndrome. Methods Thirty six subjects were identified by medical record search and divided into four groups based on situs status and type of CVM as follows: SA and complex CVM (group 1); SA and simple CVM (group 2); situs solitus and complex CVM (group 3); and situs solitus and simple CVM (group 4). Phenotype was assessed with a clinical questionnaire, nasal nitric oxide (NO) level, and pulmonary function testing. Those with complex CVM underwent additional testing for variants in genes involved in ciliary structure and function. Results The mean nasal NO level was significantly lower among all subjects with complex CVM regardless of situs anomalies (groups 1 and 3). There was no significant difference in respiratory symptoms or lung function among the four groups. No bi‐allelic genetic mutations were detected among patients with complex CVM. Conclusions This study identified a relatively lower mean nasal NO level, suggestive of relative ciliary dyskinesia, among subjects with complex CVM. Pulmonary function and clinical symptoms did not reflect significant pulmonary disease among those with complex CVM.

Ciliopathy gene variants and perioperative respiratory outcomes in infants with heterotaxy syndrome and congenital heart disease

“…While it is a recognized limitation, given that PCD is typically clinically diagnosed through functional testing of respiratory cilia, our review focused on genetic testing. Previous studies in CHD population demonstrated a high rate of abnormal ciliary function by nasal biopsy or nNO testing that associated with postoperative respiratory complications [30][31][32]. The 3 infants in our cohort who had nasal biopsies all did not have a genetic diagnosis of PCD, but two were treated as PCD on follow up.…”