Genetic Insights in 24 Chinese Pediatric Patients with Difficult-to-Diagnose Respiratory Diseases

Background: This study aimed to evaluate the diagnostic yield of exome sequencing in pediatric patients with challenging respiratory diseases and to map genotype-phenotype relationships in genetically confirmed cases. Methods: A retrospective study was conducted on 24 children with challenging-to-diagnose respiratory diseases in our hospital from January 2018 to October 2022. Case clinical features, imaging characteristics, laboratory results, and genetic testing results were reviewed. Results: A total of 24 cases were evaluated. The mean age at diagnosis was 3.81 ± 3.16 years, and the mean age of disease onset was 2.32 ± 2.28 years. Clinical manifestations included cough and expectoration (22 cases), recurrent wheezing (10 cases), and malnutrition (7 cases). Bronchoscopies of 19 cases revealed endobronchial inflammation and abundant accumulation of airway secretions, while computed tomography scans revealed 14 cases with bronchiectasis. Pulmonary function testing revealed 10 cases with obstructive ventilation dysfunction. Sputum cultures obtained from 5 patients were positive for bacterial growth. Genetic testing results revealed gene variants in 11 cases, including 2 cases with cystic fibrosis (CF), 4 cases with primary ciliary dyskinesia (PCD), and 5 cases with immunodeficiencies. Five cases carried at least one CFTR variant, including 2 CF cases, 2 bronchopulmonary dysplasia cases, and 1 patient with asthma. Conclusions: Children with challenging-to-diagnose respiratory diseases may be affected by CF, PCD, or immunodeficiencies. Genetic sequencing offers new avenues for accurate diagnosis and can contribute to a more comprehensive understanding of the disease spectrum.