When to worry about inherited bone marrow failure and myeloid malignancy predisposition syndromes in the setting of a hypocellular marrow

With our increasing understanding of inherited marrow failure and myeloid malignancy predisposition syndromes, it has become clear that there is a wide phenotypic spectrum and that these diseases must be considered in the differential diagnosis of both children and adults with unexplained defects in hematopoiesis. Moreover, these conditions are not as rare as previously believed and may present as aplastic anemia, myelodysplastic syndrome, or malignancy over a range of ages. Establishing the correct diagnosis is essential because it has implications for treatment, medical management, cancer screening, and family planning. Our goal is to highlight insights into the pathophysiology of these diseases, review cryptic presentations of these syndromes, and provide useful references for the practicing hematologist.