Genetic predisposition syndromes: when should they be considered in the work-up of MDS?

Best Pract Res Clin Haematol. 2015 Mar;28(1):55-68. doi: 10.1016/j.beha.2014.11.004. Epub 2014 Nov 12.


Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by cytopenias, ineffective hematopoiesis, myelodysplasia, and an increased risk of acute myeloid leukemia (AML). While sporadic MDS is primarily a disease of the elderly, MDS in children and young and middle-aged adults is frequently associated with underlying genetic predisposition syndromes. In addition to the classic hereditary bone marrow failure syndromes (BMFS) such as Fanconi Anemia and Dyskeratosis Congenita, in recent years there has been an increased awareness of non-syndromic familial MDS/AML predisposition syndromes such as those caused by mutations in GATA2, RUNX1, CEBPA, and SRP72 genes. Here, we will discuss the importance of recognizing an underlying genetic predisposition syndrome a patient with MDS, will review clinical scenarios when genetic predisposition should be considered, and will provide a practical overview of the common BMFS and familial MDS/AML syndromes which may be encountered in adult patients with MDS.

Keywords: CEBPA; Congenital Amegakaryocytic Thrombocytopenia; Diamond-Blackfan Anemia; Dyskeratosis Congenita; Emberger Syndrome; FPD/AML; Fanconi Anemia; GATA2; MDS; MonoMac; RUNX1; SRP72; Severe Congenital Neutropenia; Shwachman-Diamond Syndrome; bone marrow failure syndromes; familial MDS; familial leukemia; genetic predisposition; myelodysplastic syndromes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Aged
  • Antineoplastic Agents / therapeutic use
  • CCAAT-Enhancer-Binding Proteins / genetics
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Dyskeratosis Congenita / diagnosis
  • Dyskeratosis Congenita / genetics*
  • Dyskeratosis Congenita / pathology
  • Fanconi Anemia / diagnosis
  • Fanconi Anemia / genetics*
  • Fanconi Anemia / pathology
  • GATA2 Transcription Factor / genetics
  • Genetic Predisposition to Disease*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Mutation*
  • Myelodysplastic Syndromes / diagnosis
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / pathology
  • Myelodysplastic Syndromes / therapy
  • Signal Recognition Particle / genetics


  • Antineoplastic Agents
  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, human
  • Core Binding Factor Alpha 2 Subunit
  • GATA2 Transcription Factor
  • GATA2 protein, human
  • RUNX1 protein, human
  • SRP72 protein, human
  • Signal Recognition Particle