Tummala Hemanth, Walne Amanda, Dokal Inderjeet
Centre for Genomics and Child Health, Blizard Institute, Barts and The London Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
Department of Haematology, Barts Health, London, UK.
Expert Rev Hematol. 2022 Aug;15(8):685-696. doi: 10.1080/17474086.2022.2108784. Epub 2022 Aug 8.
Dyskeratosis congenita (DC) is a multisystem syndrome characterized by mucocutaneous abnormalities, bone marrow failure, and predisposition to cancer. Studies over the last 25 years have led to the identification of 18 disease genes. These have a principal role in telomere maintenance, and patients usually have very short/abnormal telomeres. The advances have also led to the unification of DC with a number of other diseases, now collectively referred to as the telomeropathies or telomere biology disorders.
Clinical features, genetics, and biology of the different subtypes. Expert view on diagnosis, treatment of the hematological complications and future.
As these are very pleotropic disorders affecting multiple organs, a high index of suspicion is necessary to make the diagnosis. Telomere length measurement and genetic analysis of the disease genes have become useful diagnostic tools. Although hematological defects can respond to danazol/oxymetholone, the only current curative treatment for these is hematopoietic stem cell transplantation (HSCT) using fludarabine-based conditioning protocols. New therapies are needed where danazol/oxymetholone is ineffective and HSCT is not feasible.
先天性角化不良（DC）是一种多系统综合征，其特征为黏膜皮肤异常、骨髓衰竭和易患癌症。过去25年的研究已鉴定出18个致病基因。这些基因在端粒维持中起主要作用，患者的端粒通常非常短/异常。这些进展还导致DC与其他一些疾病合并，现在统称为端粒病或端粒生物学障碍。
不同亚型的临床特征、遗传学和生物学。专家对诊断、血液学并发症的治疗及未来的看法。
由于这些是影响多个器官的多效性疾病，因此诊断时需要高度怀疑。端粒长度测量和致病基因的遗传分析已成为有用的诊断工具。尽管血液学缺陷对达那唑/羟甲烯龙有反应，但目前唯一的治愈性治疗方法是使用基于氟达拉滨的预处理方案进行造血干细胞移植（HSCT）。在达那唑/羟甲烯龙无效且HSCT不可行的情况下，需要新的治疗方法。
