Inherited bone marrow failure syndromes are a group of genetic disorders associated with bone marrow production defects resulting in single or multiple cytopenias. Many of these disorders predispose the patient to hematologic and nonhematologic malignancies, requiring life-long follow-up. A positive family history of hematologic disorders or malignancies is frequent, as these disorders commonly run in families, and selection of family members as potential bone marrow donors should be performed with caution to avoid transplanting potentially defective stem cells. This review highlights the most common genetic disorders associated with bone marrow failure.
Inherited bone marrow failure disorders (IBMFSs) are genetic in nature, mostly familial.
IBMFSs are usually but not always present in infancy or childhood.
IBMFSs may predispose to hematologic and nonhematologic malignancies.
IBMFSs require life-long follow-up, usually annually, or as needed.
Bone marrow transplantation may cure the marrow defect, after trial of prednisone, anabolic steroids, or growth factors in some of these entities.
The inherited bone marrow failure syndromes (IBMFSs) are a group of genetic disorders associated with inadequate bone marrow (BM) production of 1 or more blood cell lineages ( Table 1 ). Although mostly inherited, a de novo gene mutation may occur during early embryogenesis. These disorders are rare, but are clinically important due to life-threatening cytopenias and propensity to progress to severe aplastic anemia (AA), myelodysplastic syndromes (MDS), acute leukemia (AL), and other nonhematologic malignancies. Traditionally, IBMFSs have been divided into multilineage cytopenias, such as Fanconi anemia (FA), dyskeratosis congenita, Shwachman-Diamond syndrome, congenital amegakaryocytic thrombocytopenia, and unilineage cytopenia, such as Diamond-Blackfan anemia, severe congenital neutropenia, thrombocytopenia with absent radii, and congenital dyserythropoietic anemia. However, with advances in molecular and genetic studies, these disorders may be classified according to their impact on cellular function, such as DNA repair, telomere maintenance, and ribosomal biogenesis. The estimated annual incidence of IBMFS is approximately 65 per million live births.