Background: Primary ciliary dyskinesia (PCD) represents a group of rare hereditary disorders characterised by deficient ciliary airway clearance that can be associated with laterality defects. We aimed to describe the underlying gene defects, geographical differences in genotypes and their relationship to diagnostic findings and clinical phenotypes.Methods: Genetic variants and clinical findings (age, sex, body mass index, laterality defects, forced expiratory volume in 1 s (FEV₁)) were collected from 19 countries using the European Reference Network's ERN-LUNG international PCD Registry. Genetic data were evaluated according to American College of Medical Genetics and Genomics guidelines. We assessed regional distribution of implicated genes and genetic variants as well as genotype correlations with laterality defects and FEV₁.Results: The study included 1236 individuals carrying 908 distinct pathogenic DNA variants in 46 PCD genes. We found considerable variation in the distribution of PCD genotypes across countries due to the presence of distinct founder variants. The prevalence of PCD genotypes associated with pathognomonic ultrastructural defects (mean 72%, range 47–100%) and laterality defects (mean 42%, range 28–69%) varied widely among countries. The prevalence of laterality defects was significantly lower in PCD individuals without pathognomonic ciliary ultrastructure defects (18%). The PCD cohort had a reduced median FEV₁z-score (−1.66). Median FEV₁z-scores were significantly lower inCCNO(−3.26),CCDC39(−2.49) andCCDC40(−2.96) variant groups, while the FEV₁z-score reductions were significantly milder inDNAH11(−0.83) andODAD1(−0.85) variant groups compared to the whole PCD cohort.Conclusion: This unprecedented multinational dataset of DNA variants and information on their distribution across countries facilitates interpretation of the genetic epidemiology of PCD and indicates that the genetic variant can predict diagnostic and phenotypic features such as the course of lung function.

Primary ciliary dyskinesia (PCD) is caused by pathogenetic variants in more than 55 genes. PCD is associated with early-onset chronic wet cough and rhinosinusitis, laterality defects, middle ear disease and reduced fertility. The clinical presentation is heterogeneous, and diagnosis often relies on multiple tests. The American Thoracic Society (ATS) and European Respiratory Society (ERS) have previously developed separate guidelines for diagnosis. Here, ERS and ATS members systematically reviewed the literature on diagnostic tools used in practice and developed unified evidence-based guidelines for PCD diagnosis using Grading of Recommendations, Assessment, Development and Evaluations methodology, and a transparent process of decision-making using evidence-to-decision frameworks. The Task Force panel formulated three PICO (Patients, Intervention, Comparison, Outcome) questions and three narrative questions. The accuracies of high-speed video microscopy, immunofluorescence and nasal nitric oxide were compared to a reference test of transmission electron microscopy and/or genetics. The panel gives a strong recommendation for use of high-speed video microscopy, immunofluorescence and nasal nitric oxide as adjunct tests to transmission electron microscopy and/or genetics for PCD diagnosis. However, no adjunct test is suitable as a standalone test to diagnose PCD and no single adjunct or reference test is suitable to exclude PCD. Pursuing a genetic diagnosis is encouraged owing to the implications for management. The panel emphasises that tests should meet a minimum standard and proposes that patients are evaluated at a referral centre experienced in diagnosis. The pre-test probability based on symptoms should be considered when interpreting results.

Prematurity and low birth weight are significant predictors of perinatal morbidity and mortality and are influenced by the overall health and socioeconomic status of the pregnant mother. Although Cyprus is characterized by the highest prematurity rate in Europe (13.1% in 2014), the relationship between maternal health and socioeconomic characteristics with prematurity and low birth weight has never been investigated. We aimed to investigate the association of maternal demographic, clinical and socioeconomic characteristics with premature delivery and low neonatal birth weight in Cyprus. In a case-control design, questionnaire data were collected from 348 women who gave birth prematurely (cases) and 349 women who gave birth at term (controls). Information was obtained on gestation duration and birth weight as well as maternal demographic, socioeconomic and clinical profiles, including parameters such as smoking, body mass index, alcohol consumption, presence of gestational diabetes and mental health factors. Premature delivery was associated with greater maternal age (OR: 1.12, 95% CI: 1.06–1.18), absence of gestational diabetes (OR: 0.53, 95% CI: 0.30–0.97), long working hours (OR: 3.77, 95% CI: 2.08–6.84) and emotional stress (OR: 8.5, 95% CI: 3.03–23.89). Within the cases group, emotional stress was also associated with lower birth-weight (β: -323.68 (95% CI: -570.36, − 77.00). The findings of this study demonstrate the positive association of maternal psychological factors, working conditions as well as maternal age with prematurity and low birth weight in Cyprus. Additional, prospective, studies are needed in the country to further investigate these associations and inform public health intervention measures.