The most common cause of inherited bone marrow failure is Fanconi anemia, an autosomal recessive disorder caused by defects in the DNA damage repair pathway. Patients with Fanconi anemia have growth and development anomalies, bone marrow failure and leukemia, and a predisposition to cancers of the aerodigestive tract. The second most common cause of inherited bone marrow failure is dyskeratosis congenita, a disease characterized by bone marrow failure, oral leukoplakia, pigmentation changes in the skin, and nail dystrophy. Multiple genetic mutations are associated with dyskeratosis congenita, but they all cause defects in telomere maintenance. In Diamond-Blackfan anemia, progression to MDS or aplastic anemia can occur, but Diamond-Blackfan anemia is typically characterized by pure red blood cell aplasia. Schwackman-Diamond syndrome is characterized by pancreatic exocrine dysfunction, neutropenia, and metaphyseal dysostosis, but progression to aplastic anemia, MDS, and AML is not uncommon. Diamond-Blackfan anemia and Schwackman-Diamond syndrome appear to stem from defective ribosomal RNA processing. It is important to identify whether bone marrow failure is related to an inherited disorder because the choice of treatment and subsequent patient outcomes will be affected.1
- Fanconi anemia.
1. Alter BP. Diagnosis, genetics, and management of inherited bone marrow failure syndromes. Hematology 2007;2007:29–39.
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