Clinical Spectrum and Organ Involvement in Telomere Biology Disorders: a Single-centre Cohort
Year: 2026
Type: article
Study design: Observational Study
Abstract: Introduction Telomere biology disorders are inherited conditions caused by defects in telomere maintenance. The clinical spectrum is broad, ranging from severe childhood syndromes to adult-onset presentations such as bone marrow failure, isolated cytopenias, pulmonary fibrosis, and liver disease. This phenotypic variability creates significant diagnostic challenges in clinical practice. Objectives To describe the diversity and proportional distribution of clinical presentations in patients with telomere biology disorders, emphasizing hematological, pulmonary, and hepatic involvement at diagnosis. Material and Methods A retrospective observational cohort study was conducted with patients followed at a bone marrow failure referral clinic. The disease was defined by pathogenic germline variants in telomere-related genes associated with short telomeres, or by critically short telomeres without an identified variant. Clinical, laboratory, imaging, and biopsy data were extracted from medical records. Telomere length was measured using Southern blot analysis. The study was approved by the institutional Research Ethics Committee. Results The cohort included 56 patients, with a median age at diagnosis of 33-years (range 2‒78), and 53% were female. Telomere length was below the 10th percentile for age in 75% of patients. Hematological involvement was the most frequent manifestation (60%), followed by pulmonary abnormalities (27%) and hepatic involvement (18%). Nine patients (16%) were asymptomatic at initial evaluation. Among symptomatic presentations, isolated bone marrow failure (39%), pulmonary and/or liver disease (23%), and dyskeratosis congenita/Hoyeraal-Hreidarsson syndrome (18%) were the leading phenotypes. Complete blood count abnormalities were present in 73% of patients, with thrombocytopenia being the most frequent cytopenia (61%). The TERT gene had the highest mutation frequency in the analyzed cohort, 53%, followed by TERC (17%), RTEL1 (13%), TINF2 (13%), POT1 (4%), and DKC1 (2%). Discussion This study demonstrated a considerable proportion of extra-hematological involvement and asymptomatic cases. Although hematological pathology remains the primary finding, systematic screening identified pulmonary and hepatic morbidities in a substantial minority, highlighting the multisystemic nature of the condition. A trend towards inferior survival was observed among patients with hematological involvement. Conclusion Telomere biology disorders manifest as a heterogeneous clinical continuum. Hematological involvement is the most prevalent presentation; however, the frequent detection of pulmonary and hepatic comorbidities reinforces the need for systematic screening and multidisciplinary medical follow-up.
Institutions: Universidade de São Paulo, Clinics Hospital of Ribeirão Preto
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223154555