Germline predispositions to myeloid malignancies: Across the lifespan

Germline predisposition syndromes to myeloid malignancies have been recognized increasingly over the last decade. Although many of these genetic syndromes present early in life, the age at which a hematopoietic malignancy develops can vary widely depending on the specific gene involved and its role in hematopoiesis. Herein, we aim to review age-related penetrance and phenotype of key germline predisposition syndromes including: SAMD9/9L, GATA2, inherited bone marrow failure syndromes, RUNX1, CEBPA, TP53, and DDX41. We describe optimal diagnostic strategies for these patients, and explain how recognition of germline predisposition allows for the development of optimal treatment plan for the affected individual and counseling of at-risk family members.