Inherited Bone Marrow Failure Syndromes – Challenges and Updates

Abstract: Congenital or inherited bone marrow failure syndromes are hereditary syndromes of diverse nature which are characterized by inadequate production of blood cells causing cytopenias. Failure of bone marrow can be limited to one or more lineages of blood cells, along with symptoms specified to lineage, through it can affect all cell lineages leading to clinical picture like aplastic anemia. These syndromes are genetic diseases of heterogenous nature caused by germline mutations affecting basic pathways of cell including telomerase biology, biogenesis of ribosomes, structural proteins, and repair of DNA. Common inherited bone marrow failure syndromes consist of Schwachman – Diamond syndrome, Diamond – Blackfan anemia, Fanconi anemia, and Dyskeratosis Congenita. These syndromes have different prognosis and tendency to develop solid or hematological malignancies. Therefore, the adequate diagnosis of these disorders and their differentiation from other bone marrow failure syndromes and/or other etiologies of the boe marrow failure is very significant for surveillance and management of patients. Acquired causes may also lead to bone marrow failure including radiations, chemicals, drugs, immune diseases, viral infections, myelodysplastic syndromes, large granular lymphocytic leukemia, or paroxysmal nocturnal hemoglobinuria (PNH). Inherited bone marrow failure syndromes are heritable and affects family members as well, therefore need genetic counselling. In this review, differential diagnosis, various causes, and their pathogenesis are discussed for better understanding of inherited bone marrow failure syndromes.