Myeloid neoplasms with germline predisposition have been recognized increasingly over the past decade with numerous newly described disorders. Penetrance, age of onset, phenotypic heterogeneity, and somatic driver events differ widely among these conditions and sometimes even within family members with the same variant, making risk assessment and counseling of these individuals inherently difficult. In this review, we will shed light on high malignant penetrance (, , , and ) versus variable malignant penetrance syndromes (, , , , and various bone marrow failure syndromes) and their clinical features, such as variant type and location, course of disease, and prognostic markers. We further discuss the recommended management of these syndromes based on penetrance with an emphasis on somatic aberrations consistent with disease progression/transformation and suggested timing of allogeneic hematopoietic stem cell transplant. This review will thereby provide important data that can help to individualize and improve the management for these patients.

中文翻译：

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骨髓肿瘤的种系易感性：高外显率疾病与可变外显率疾病的特征和治疗

在过去的十年中，随着许多新描述的疾病，人们越来越多地认识到具有种系易感性的骨髓肿瘤。这些疾病之间的外显率、发病年龄、表型异质性和体细胞驱动事件差异很大，有时甚至在具有相同变异的家庭成员中也存在很大差异，这使得对这些个体进行风险评估和咨询本身就很困难。在这篇综述中，我们将阐明高恶性外显率（、、、和）与可变恶性外显率综合征（、、、、、和各种骨髓衰竭综合征）及其临床特征，例如变异类型和位置、病程和预后标志物。我们进一步讨论基于外显率的这些综合征的推荐管理，重点是与疾病进展/转化一致的体细胞畸变，并建议异基因造血干细胞移植的时机。因此，本次审查将提供重要数据，有助于个性化和改进这些患者的管理。