title: Hereditary Predispositions to Myelodysplastic Syndrome.
abstract: Myelodysplastic syndromes (MDS) are heterogeneous clonal hematopoietic disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, and peripheral cytopenias. Familial forms of MDS have traditionally been considered rare, especially in adults; however, the increasing availability of somatic and germline genetic analyses has identified multiple susceptibility loci. Bone marrow failure syndromes have been well-described in the pediatric setting, e.g., Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SBS), hallmarked by clinically-recognizable phenotypes (e.g., radial ray anomalies in FA) and significantly increased risks for MDS and/or acute myeloid leukemia (AML) in the setting of bone marrow failure. However, additional families with multiple cases of MDS or AML have long been reported in the medical literature with little known regarding potential hereditary etiologies. Over the last decade, genomic investigation of such families has revealed multiple genes conferring inherited risks for MDS and/or AML as the primary malignancy, including RUNX1, ANKRD26, DDX41, ETV6, GATA2, and SRP72. As these syndromes are increasingly appreciated in even apparently de novo presentations of MDS, it is important for hematologists/oncologists to become familiar with these newly-described syndromes. Herein, we provide a review of familial MDS syndromes and practical aspects of management in patients with predisposition syndromes.
authors.affiliation: Department of Clinical Cancer Genetics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. sabannon@mdanderson.org.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Bannon
authors.affiliation: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. cdinardo@mdanderson.org.
authors.forename: Courtney D
authors.initials: CD
authors.lastname: DiNardo
mesh_terms: D000741:Anemia, Aplastic / Q000235:genetics*; D001855:Bone Marrow Diseases / Q000235:genetics*; D000080983:Bone Marrow Failure Disorders; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics; D005260:Female; D050989:GATA2 Transcription Factor / Q000235:genetics; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics*; D040941:Heredity; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D018271:Signal Recognition Particle / Q000235:genetics; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D053487:DEAD-box RNA Helicases; D050989:GATA2 Transcription Factor; D036341:Intercellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D018271:Signal Recognition Particle; D000097764:ETS Translocation Variant 6 Protein; C583630:ANKRD26 protein, human; C494711:GATA2 protein, human; C493728:RUNX1 protein, human; C503636:SRP72 protein, human; C501226:DDX41 protein, human
keywords: MDS; familial; genetic counseling; germline; hereditary; predisposition