Department of Pediatrics, Section of Hematology, Oncology and Bone Marrow Transplantation, University of Colorado, Aurora, CO, USA.
J Genet Couns. 2022 Apr;31(2):433-446. doi: 10.1002/jgc4.1510. Epub 2021 Sep 27.
The timely identification of germline genetic causes of pediatric bone marrow failure (BMF) impacts medical screening practices, family counseling, therapeutic decision-making, and risk of progression to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). At diagnosis, treatment decisions need to be made quickly to mitigate risks associated with profound cytopenias. As genetic testing options are rapidly evolving, an efficient multi-disciplinary approach and algorithm, including early involvement of a genetics team, is needed to expedite diagnosis and therapeutic decision-making. This process aids in the identification of appropriate candidates for molecular genetic testing. We present our single center experience reviewing the implementation of genetic counseling and a diagnostic and therapeutic algorithm used to guide genetic evaluation of pediatric BMF. Disease-specific next-generation sequencing (NGS) panels were most often pursued in patients who presented with a clinical phenotype consistent with a known inherited BMF syndrome and when trying to reduce incidental or uninformative results. Broader BMF NGS panels were most often utilized when unable to narrow the suspected etiology to a single disorder. Whole exome sequencing helped with optimizing treatment decision-making in higher risk children with BMF who required expedited hematopoietic stem cell transplantation. The experience has led to improvements to our process for evaluating patients with BMF.
及时识别儿科骨髓衰竭（BMF）的种系遗传原因会影响医学筛查实践、家庭咨询、治疗决策以及进展为骨髓增生异常综合征（MDS）或急性髓系白血病（AML）的风险。在诊断时，需要迅速做出治疗决策，以减轻与严重细胞减少相关的风险。由于基因检测选项正在迅速发展，需要一种有效的多学科方法和算法，包括早期涉及遗传团队，以加快诊断和治疗决策。这个过程有助于确定适合分子遗传学检测的合适人选。我们介绍了我们的单中心经验，回顾了遗传咨询的实施和诊断及治疗算法的应用，以指导儿科 BMF 的遗传评估。疾病特异性下一代测序（NGS）面板最常用于临床表现与已知遗传性 BMF 综合征一致的患者，以及试图减少偶然或无信息结果时。当无法将疑似病因缩小到单一疾病时，通常会使用更广泛的 BMF NGS 面板。全外显子组测序有助于优化需要加速造血干细胞移植的 BMF 高风险儿童的治疗决策。这一经验促使我们改进了评估 BMF 患者的流程。
