Germline Predisposition to Myelodysplastic Syndromes.

ABSTRACT: While germline predisposition to myelodysplastic syndromes is well-established, knowledge has advanced rapidly resulting in more cases of inherited hematologic malignancies being identified. Understanding the biological features and main clinical manifestations of hereditary hematologic malignancies is essential to recognizing and referring patients with myelodysplastic syndrome, who may underlie inherited predisposition, for appropriate genetic evaluation. Importance lies in individualized genetic counseling along with informed treatment decisions, especially with regard to hematopoietic stem cell transplant-related donor selection. Future studies will improve comprehension of these disorders, enabling better management of affected patients and their families.

Approach Toward Germline Predisposition Syndromes in Patients with Hematologic Malignancies.

PURPOSE OF REVIEW: Hematologic malignancies were previously thought to be primarily sporadic cancers without germline predispositions. However, over the last two decades, with the widespread use of next generation sequencing (NGS), there have been several genes have been identified that carry a risk of inheriting hematologic malignancies. Identification of individuals with hereditary hematologic malignancies (HHM) involves a high index of suspicion and careful attention to family history, clinical features, and variant allele frequency on somatic NGS panels. RECENT FINDINGS: Over the last several years, many genetic predisposition syndromes have been recognized to have unique features with both hematologic and non-hematologic co-morbidities. Multidisciplinary evaluation, including genetic counseling, is critical to optimizing diagnostic testing of individuals and at-risk family members. Prompt recognition of affected patients is imperative not only for personalized surveillance strategies but also for proper donor selection for those undergoing stem cell transplantation to avoid familial donors who also may share the same germline mutation. Herein, we describe our approach to recognizing patients suspected to carry a germline predisposition to hematologic malignancies and evaluation within a hereditary hematologic malignancies clinic (HHMC).