Cancer-Prone Inherited Bone Marrow Failure, Myelodysplastic, and Acute Myeloid Leukemia Syndromes

The inherited bone marrow failure syndromes (IBMFS) are a clinically and molecularly heterogeneous group of cancer-prone disorders. Many IBMFS are associated with specific clinical characteristics and/or dysmorphic features. The IBMFS associated with increased risk of leukemia, myelodysplastic syndrome (MDS), and certain solid tumors include Fanconi anemia, dyskeratosis congenita, and Diamond Blackfan anemia. Individuals with Shwachman Diamond syndrome, severe congenital neutropenia, congenital amegakaryocytic thrombocytopenia, or thrombocytopenia absent radius syndrome may be at increased risk of leukemia. Patients with IBMFS have syndrome-specific pathogenic germline variants in genes critical in DNA repair, telomere biology, ribosome biology, or hematopoiesis.