Age-Related Cerebral Ventriculomegaly occurs in Patients with Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a genetic disorder causing motile ciliary dysfunction primarily affecting the respiratory and reproductive systems. However, the impact of PCD on the central nervous system, through dysfunction of motile cilia in multiciliated ependymal cells, remains poorly understood. We hypothesized that patients with PCD exhibit sub-clinical ventriculomegaly due to ependymal ciliary dysfunction, which may influence neuropsychiatric diagnoses. We demonstrated highly specific expression levels of known PCD-related genes in human brain ependymal cells (p<0.0001), supporting their potential role in regulating ependymal ciliary function. Computed tomography sinus images from patients with PCD (n=33) and age/sex-matched controls (n=64) were analysed. Patients with PCD displayed significantly larger ventricular areas (p<0.0001) and Evans index (p<0.01), indicating ventriculomegaly that was consistent across all genetic subgroups. Ventricular enlargement correlated positively with increasing age in patients with PCD compared to controls (p<0.001). Chart review demonstrated a high prevalence (39%) of neuropsychiatric/neurological disorders in adult PCD patients that did not correlate with degree of ventriculomegaly. Our findings suggest that patients with PCD may have unrecognized, mild ventriculomegaly potentially due to ependymal ciliary dysfunction which correlates with ageing. Further study is required to determine if ventricular enlargement contributes to neuropsychiatric/neurological or other morbidity in PCD.