Hematopoietic development: a gap in our understanding of inherited bone marrow failure

Inherited bone marrow failure syndromes (IBMFS) represent a heterogeneous group of multisystem disorders that typically present with cytopenia in early childhood. Efforts to understand the underlying hematopoietic stem cell (HSC) losses have generally focused on postnatal hematopoiesis. However, reflecting the role of many of the involved genes in core cellular functions and the diverse nonhematologic abnormalities seen in patients at birth, studies have begun to explore IBMFS manifestations during fetal development. Here, I consider the current evidence for fetal deficits in the HSC pool and highlight emerging concepts regarding the origins and unique pathophysiology of hematopoietic failure in IBMFS.