Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
Curr Opin Pediatr. 2023 Feb 1;35(1):75-83. doi: 10.1097/MOP.0000000000001196. Epub 2022 Nov 10.
Recent advances in diagnosis and treatment of inherited bone marrow failure syndromes (IBMFS) have significantly improved disease understanding and patient outcomes. Still, IBMFS present clinical challenges that require further progress. This review aims to provide an overview of the current state of diagnosis and treatment modalities of the major IBMFS seen in paediatrics and present areas of prioritization for future research.
Haematopoietic cell transplantation (HCT) for IBMFS has greatly improved in recent years, shifting the research and clinical focus towards cancer predispositions and adverse effects of treatment. Each year, additional novel genes and pathogenic variants are described, and genotype-phenotype mapping becomes more sophisticated. Moreover, novel therapeutics exploring disease-specific mechanisms show promise to complement HCT and treat patients who cannot undergo current treatment options.
Research on IBMFS should have short-term and long-term goals. Immediate challenges include solidifying diagnostic and treatment guidelines, cancer detection and treatment, and continued optimization of HCT. Long-term goals should emphasize genotype-phenotype mapping, genetic screening tools and gene-targeted therapy.
近年来，遗传性骨髓衰竭综合征（IBMFS）的诊断和治疗进展显著提高了人们对疾病的认识和患者的预后。然而，IBMFS 仍存在临床挑战，需要进一步取得进展。本综述旨在概述儿科常见 IBMFS 的诊断和治疗方式，并提出未来研究的优先领域。
近年来，造血干细胞移植（HCT）在 IBMFS 中的应用取得了很大进展，研究和临床重点转向了癌症易感性和治疗的不良反应。每年都有更多新的基因和致病性变异被描述，基因型-表型相关性也变得更加复杂。此外，探索疾病特异性机制的新疗法有望补充 HCT，并治疗那些不能接受现有治疗方案的患者。
IBMFS 的研究应该有短期和长期目标。近期的挑战包括巩固诊断和治疗指南、癌症的检测和治疗，以及继续优化 HCT。长期目标应强调基因型-表型相关性、遗传筛查工具和基因靶向治疗。
