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.
Highlights
Thrombocytopenia 2Associated with germline mutations in the 51 untranslated region of the gene Ankyrin Repeat Domain 26 (ANKRD26) on chromosome 10p12, Thrombocytopenia 2 is an autosomal dominant disorder that is characterized by moderate thrombocytopenia with or without bleeding propensity, similar to FPD/acute myeloid leukemia (AML)
Myelodysplastic syndromes (MDS) are clonal neoplastic blood disorders characterized by ineffective hematopoiesis, peripheral cytopenias, bone marrow dysplasia, and an increased risk of acute myeloid leukemia (AML)
As genetic sequencing has become increasingly integrated into clinical practice, clearly defined syndromes have emerged, termed familial MDS/acute myeloid leukemia (AML) predisposition syndromes [2]
Summary
Associated with germline mutations in the 51 untranslated region of the gene Ankyrin Repeat Domain 26 (ANKRD26) on chromosome 10p12, Thrombocytopenia 2 is an autosomal dominant disorder that is characterized by moderate thrombocytopenia with or without bleeding propensity, similar to FPD/AML. In the initial description of ANKRD26 mutations, Pippucci et al [4] sequenced the coding region of a previously identified candidate locus at 10p (THC2) for inherited thrombocytopenia, revealing only polymorphisms. Individuals with ANKRD26 are clinically difficult to distinguish from those with FPD/AML and surveillance recommendations are similar, including a bone marrow biopsy with cytogenetics at diagnosis and physical exam and blood work at regular intervals. Similar to other inherited predispositions to leukemia, care should be taken to perform genetic testing in family members should an allogeneic stem cell transplant be required [2]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
