Diagnosis and Management of Pulmonary Manifestations of Telomere Biology Disorders

Abstract

Purpose of review: Telomere biology disorders (TBD) are a group of genetic disorders characterized by premature shortening of telomeres, resulting in accelerated aging of somatic cells. This often leads to major multisystem organ dysfunction, and TBDs have become increasingly recognized as a significant contributor to numerous disease processes within the past 10-15 years. Both research and clinical practice in this field are rapidly evolving.

Recent findings: A subset of patients with TBD suffers from interstitial lung disease, most commonly pulmonary fibrosis. Often, the clinical presentation is indistinguishable from other forms of lung fibrosis. There are no pathognomonic radiographic or histological features, and a high level of suspicion is therefore required. Telomere evaluation is thus crucial to establishing the diagnosis. This review details the clinical presentation, objective evaluation, indicated genetic testing, and recommended management strategies for patients affected by interstitial lung disease associated with TBDs. Our goal is to empower pulmonologists and other healthcare professionals who care for these patients to provide appropriate and personalized care for this population.

Keywords: Interstitial lung disease; Lung fibrosis; Telomere biology disorders; Telomere length.

Fig. 1

Representative high-resolution computed tomography (HRCT) coronal (A, D, and G) and axial (B, C, E, F, H, and I) images from adults with pulmonary fibrosis in the setting of pathogenic variants in telomere-related genes. A–C A 76-year-old male heterozygous for RTEL1 (c.3724 + 139 G > A). D–F A 64-year-old female heterozygous for TERT (c.1864 C > T, (p.R622C)). G–I A 59-year-old male heterozygous for TERT (c.2030 G > A, p.Gly677Asp)