Division of Hematology, Mayo Clinic, Rochester, MN.
Center for Individualized Medicine, Health Sciences Research, Mayo Clinic, Rochester, MN.
Mayo Clin Proc. 2018 Jul;93(7):834-839. doi: 10.1016/j.mayocp.2018.05.015.
Short telomere syndromes (STSs) are accelerated aging syndromes with multisystemic manifestations that present complex management challenges. In this article, we discuss a single-institution experience in diagnosing and managing patients with inherited STSs. In total, we identified 17 patients with short telomeres, defined by flow-fluorescence in-situ hybridization telomere lengths of less than first centile in granulocytes/lymphocytes OR the presence of a characteristic germline pathogenic variant in the context of a highly suggestive clinical phenotype. Genetic variations in the telomere complex were identified in 6 (35%) patients, with 4 being known pathogenic variants involving TERT (n=2), TERC (n=1), and DKC1 (n=1) genes, while 2 were variants of uncertain significance in TERT and RTEL1 genes. Idiopathic interstitial pneumonia (IIP) (n=12 [71%]), unexplained cytopenias (n=5 [29%]), and cirrhosis (n=2 [12%]) were most frequent clinical phenotypes at diagnosis. At median follow-up of 48 (range, 0-316) months, Kaplan-Meier estimate of overall survival, median (95% CI), was 182 (113, not reached) months. Treatment modalities included lung transplantation for IIP (n=5 [29%]), with 3 patients developing signs of acute cellular rejection (2, grade A2; 1, grade A1); danazol therapy for cytopenias (n=4 [24%]), with only 1 out of 4 patients showing a partial hematologic response; and allogeneic hematopoietic stem cell transplant for progressive bone marrow failure (n=2), with 1 patient dying from transplant-related complications. In summary, patients with STSs present with diverse clinical manifestations and require a multidisciplinary approach to management, with organ-specific transplantation capable of providing clinical benefit.
短端粒综合征（STSs）是一种伴有多系统表现的加速衰老综合征，具有复杂的管理挑战。在本文中，我们讨论了一家机构在诊断和管理遗传性 STSs 患者方面的经验。共有 17 名患者被诊断为短端粒，其端粒长度通过流式荧光原位杂交（FISH）测定，在粒细胞/淋巴细胞中小于第一百分位数，或在高度提示临床表型的情况下存在特征性种系致病性变异。在 6 名（35%）患者中发现了端粒复合物的遗传变异，其中 4 名是已知的致病性变异，涉及 TERT（n=2）、TERC（n=1）和 DKC1（n=1）基因，而 2 名是 TERT 和 RTEL1 基因中不确定意义的变异。特发性间质性肺炎（IIP）（n=12[71%]）、不明原因血细胞减少（n=5[29%]）和肝硬化（n=2[12%]）是诊断时最常见的临床表型。在中位数为 48（范围 0-316）个月的随访中，Kaplan-Meier 估计总生存率为 182（113，未达到）个月。治疗方法包括 IIP 患者的肺移植（n=5[29%]），其中 3 名患者出现急性细胞排斥（2 例，A2 级；1 例，A1 级）；达那唑治疗血细胞减少症（n=4[24%]），4 名患者中只有 1 名有部分血液学反应；以及进展性骨髓衰竭患者的异基因造血干细胞移植（n=2），其中 1 名患者死于移植相关并发症。总之，STSs 患者表现出多种临床表现，需要多学科方法进行管理，器官特异性移植能够提供临床获益。
