Telomere biology disorders associated with childhood interstitial lung disease

Background: Telomere biology disorders (TBDs) are rare inherited defects in telomere maintenance associated with multisystem diseases. Although pulmonary fibrosis has been well described in adults, data remain limited on childhood interstitial lung disease (chILD) related to TBDs. Purpose: This study aimed to characterize the pulmonary phenotype, genetic spectrum, and clinical course of pediatric TBD-associated chILD. Methods: We performed this registry-based cohort study using the European chILD-EU database to identify children with telomere maintenance gene variants. Their clinical data, longitudinal outcomes, telomere length (quantitative polymerase chain reaction), high-resolution computed tomography (HRCT), and histopathology findings were systematically analyzed. Results: Ten children were identified with genetically confirmed or suspected TBDs harboring variants in TERT, TERC, WRAP53, DKC1, PARN, and RTEL1. Telomere length was below the 1st age-adjusted percentile in 6 of the 8 tested patients. The HRCT findings were heterogeneous and included ground-glass opacities, reticular changes, cystic lesions, and emphysema. The histopathological patterns included cellular nonspecific interstitial pneumonia, usual interstitial pneumonia, follicular bronchiolitis, and pleuroparenchymal fibrosis. The disease course was frequently severe: 7 of the 10 patients required long-term oxygen therapy, 3 underwent hematopoietic stem cell transplantation, and 4 died during follow-up. Conclusion: TBD-associated chILD is a rare but clinically aggressive multisystem disorder with a broad radiological and histopathological spectrum. Early genetic testing and multidisciplinary management are essential since affected children may experience rapid disease progression and substantial mortality.