Genetic and clinical characteristics of familial pulmonary fibrosis patients and relatives

Familial pulmonary fibrosis (FPF) represents a subgroup of pulmonary fibrosis cases in which affected individuals have a family history of the disease. First-degree relatives in these families face an elevated risk of developing pulmonary fibrosis, highlighting the importance of genetic and clinical screening.

During ERS 2025, Dr Nathalie Veyt, resident in clinical genetics at the University Hospitals Leuven, presented the results of a study looking into the genetic basis of FPF patients and their relatives. To this end, they recruited patients with FPF and reportedly healthy first-degree relatives. Patients underwent genetic testing using a pulmonary fibrosis gene panel as well as a telomere length analysis, while their relatives were examined through genetic screening in combination with clinical assessments, including high-resolution computed tomography (HRCT) and pulmonary function testing.

The results of the study showed that in 23% of cases, a definitive monogenic cause of disease could be identified, primarily involving genes regulating telomere maintenance. A smaller proportion carried pathogenic variants in surfactant-related genes. An additional 17% of cases demonstrated variants of uncertain but possible pathogenic significance. 

Importantly, the identification of telomere-related mutations not only provides insight into pulmonary disease risk but also indicates susceptibility to extra-pulmonary manifestations, such as hematological or hepatological disorders. This underlines the need for genetic counseling and multidisciplinary follow-up for patients and their relatives.

Currently, Veyt and colleagues are focusing on the validation of novel candidate genes in unexplained families and functional studies to establish causal links between these alterations and FPF.