Division of Pediatric Hematology-Oncology, First Department of Pediatrics, National and Kapodistrian University of Athens, Aghia Sophia Children's Hospital, Full Member of ERN GENTURIS and ERN EuroBloodnet, 8 Levadias Street, Goudi, Athens, 11527, Greece.
Department of Internal Medicine, University of Patras Medical School, Rion, 26500, Greece.
Postgrad Med J. 2024 Nov 22;100(1190):879-889. doi: 10.1093/postmj/qgae102.
Defective telomerase function or telomere maintenance causes genomic instability. Alterations in telomere length and/or attrition are the primary features of rare diseases known as telomere biology disorders or telomeropathies. Recent advances in the molecular basis of these disorders and cutting-edge methods assessing telomere length have increased our understanding of this topic. Multiorgan manifestations and different phenotypes have been reported even in carriers within the same family. In this context, apart from dyskeratosis congenita, disorders formerly considered idiopathic (i.e. pulmonary fibrosis, liver cirrhosis) frequently correlate with underlying defective telomere maintenance mechanisms. Moreover, these patients are prone to developing specific cancer types and exhibit exceptional sensitivity and toxicity in standard chemotherapy regimens. The current review describes the diverse spectrum of clinical manifestations of telomere biology disorders in pediatric and adult patients, their correlation with pathogenic variants, and considerations during their management to increase awareness and improve a multidisciplinary approach.
端粒酶功能缺陷或端粒维持障碍会导致基因组不稳定。端粒长度的改变和/或损耗是被称为端粒生物学疾病或端粒病的罕见疾病的主要特征。这些疾病的分子基础的最新进展和评估端粒长度的先进方法增加了我们对这一主题的理解。即使在同一家庭的携带者中，也有报道称存在多器官表现和不同的表型。在这种情况下，除了先天性角化不良外，以前被认为是特发性的疾病（即肺纤维化、肝硬化）经常与潜在的缺陷端粒维持机制相关。此外，这些患者易发生特定类型的癌症，并对标准化疗方案表现出异常的敏感性和毒性。本综述描述了端粒生物学疾病在儿科和成年患者中的不同临床表现及其与致病性变异的相关性，以及在管理过程中的注意事项，以提高认识并改善多学科方法。
