Fiesco-Roa Moisés Ó, García-de Teresa Benilde, Leal-Anaya Paula, van 't Hek Renée, Wegman-Ostrosky Talia, Frías Sara, Rodríguez Alfredo
Laboratorio de Citogenética, Instituto Nacional de Pediatría, Ciudad de México, Mexico.
Maestría y Doctorado en Ciencias Médicas, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, Ciudad de México, Mexico.
Front Oncol. 2022 Aug 25;12:949435. doi: 10.3389/fonc.2022.949435. eCollection 2022.
Inherited bone marrow failure syndromes (IBMFS) are a complex and heterogeneous group of genetic diseases. To date, at least 13 IBMFS have been characterized. Their pathophysiology is associated with germline pathogenic variants in genes that affect hematopoiesis. A couple of these diseases also have genomic instability, Fanconi anemia due to DNA damage repair deficiency and dyskeratosis congenita/telomere biology disorders as a result of an alteration in telomere maintenance. Patients can have extramedullary manifestations, including cancer and functional or structural physical abnormalities. Furthermore, the phenotypic spectrum varies from cryptic features to patients with significantly evident manifestations. These diseases require a high index of suspicion and should be considered in any patient with abnormal hematopoiesis, even if extramedullary manifestations are not evident. This review describes the disrupted cellular processes that lead to the affected maintenance of the genome structure, contrasting the dysmorphological and oncological phenotypes of Fanconi anemia and dyskeratosis congenita/telomere biology disorders. Through a dysmorphological analysis, we describe the phenotypic features that allow to make the differential diagnosis and the early identification of patients, even before the onset of hematological or oncological manifestations. From the oncological perspective, we analyzed the spectrum and risks of cancers in patients and carriers.
遗传性骨髓衰竭综合征（IBMFS）是一组复杂且异质性的遗传性疾病。迄今为止，至少已鉴定出13种IBMFS。它们的病理生理学与影响造血的基因中的种系致病变异有关。其中一些疾病还存在基因组不稳定，由于DNA损伤修复缺陷导致范可尼贫血，以及由于端粒维持改变导致的先天性角化不良/端粒生物学障碍。患者可能有髓外表现，包括癌症以及功能或结构上的身体异常。此外，表型谱从隐匿特征到表现明显的患者各不相同。这些疾病需要高度怀疑，任何造血异常的患者都应考虑到，即使髓外表现不明显。本综述描述了导致基因组结构维持受影响的细胞过程紊乱，对比了范可尼贫血和先天性角化不良/端粒生物学障碍的畸形学和肿瘤学表型。通过畸形学分析，我们描述了即使在血液学或肿瘤学表现出现之前，也能进行鉴别诊断和早期识别患者的表型特征。从肿瘤学角度，我们分析了患者及其携带者患癌症的范围和风险。
