Abstract Rationale Primary Ciliary Dyskinesia (PCD) is a disorder of impaired mucociliary clearance that manifests with sino-oto-pulmonary disease and laterality defects typically during infancy. Despite a suggested prevalence of 1:7600, PCD remains under-recognized and under-diagnosed, with the average age of diagnosis well into childhood and often into adulthood for many patients. The morbidity and mortality of PCD is poorly understood with little research examining life expectancy and long-term outcomes. This study investigates the prevalence of severe PCD phenotypes at two large academic centers with expertise in PCD care. Methods We retrospectively analyzed data from adult and pediatric patients at the University of North Carolina and the McGill University Health Centre from 2015 to 2025. PCD diagnoses were confirmed with genetic testing or class 1 transmission electron microscopy (TEM) defect. Patients were considered as having severe disease if they had low lung function (pre-bronchodilator FEV1 ≤50% predicted), required lung transplant, or died. Demographics and cause of death were extracted from medical records, and the age of diagnosis was determined as the date of confirmatory testing either via TEM or molecular genetics. Results Of 254 adult and pediatric patients with PCD, 57 (22%) had severe PCD, including 18 (7%) who were deceased, 7 (3%) who were post-transplant, and 32 (6%) with low pulmonary function. Median age of death or transplant were 47 (IQR 37) and 52 (IQR 17) years, respectively, and the average age of those with low lung function was 46 (IQR 21) years. The largest cohort of patients were diagnosed in their fifth decade of life (13/57, 23%). The median age of diagnosis for all patients with severe disease was 31 years (IQR 35), and 61% (35) were female. Genetic testing was available for 54 of the 57 (95%) patients, with the most common pathogenic variants occurring in known severe genes CCDC39, CCDC40, CCNO or corresponding TEM defects (inner dynein arm/microtubular disorganization), totaling 22 of 57 patients (39%). Conclusions The identification and diagnosis of PCD are often delayed, and the clinical course, morbidity, and mortality of this rare disease are poorly understood, with much of the literature focusing on pediatric populations. This retrospective review of PCD in both adult and pediatric populations includes a large cohort of patients with a confirmed diagnosis and is one of few to explore characteristics of patients with severe disease, underscoring the need for further research into long-term outcomes for PCD. This abstract is funded by: Genetic Disorders of Mucociliary Clearance Consortium Grant, U54HL096458
Michaels et al. (Fri,) studied this question.