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  • Case Study
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Severe TMD/AMKL with GATA1 mutation in a stillborn fetus with Down syndrome

Nature Clinical Practice Oncology volume 4, pages 433–438 (2007)Cite this article

Abstract

Background A 34-year-old woman was referred for evaluation of a recent stillborn male fetus, gestational age 27 6/7 weeks, found to have congenital myeloid leukemia at autopsy. Autopsy findings included high weight for gestational age, hepatomegaly, and extensive intravascular leukemic infiltrates in the placenta, heart, liver, thymus, lung, kidneys, and brain. Genetic consultation and examination of photographs of the fetus revealed dysmorphic features.

Investigations Immunoperoxidase staining of placental tissue, fluorescence in situ hybridization of paraffin-embedded sections of the placenta using probes for t(12;21)(p13;q22), t(8;21)(q22;q22) and t/del(11q23), cytogenetic analysis of fetal tissue (tendon), sequence analysis of GATA1 in placental leukemic cells, and parental chromosome studies.

Diagnosis Down syndrome with in utero onset of GATA1 mutation-positive severe transient myeloproliferative disorder/acute megakaryoblastic leukemia.

Management Genetic counseling for the recurrence risk of Down syndrome on the basis of maternal age.

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Figure 1: Leukemic infiltrates at autopsy
Figure 2: Morphologic and immunophenotypic findings in placenta
Figure 3: Fluorescence in situ hybridization with RUNX1T1/RUNX1 probes in a paraffin-embedded section of placenta
Figure 4: Chromatogram showing GATA1 mutation within the first coding exon

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Acknowledgements

C Eng is a recipient of the Doris Duke Distinguished Clinical Scientist Award.

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Authors and Affiliations

  1. B Heald is a Genetic Counselor at the Center for Personalized Genetic Healthcare in the Genomic Medicine Institute and the Taussig Cancer Center, and K Zbuk is a Cancer Genomic Medicine Fellow and Crile Fellow at the Genomic Medicine Institute, at the Cleveland Clinic, Cleveland, OH, USA.,

    Brandie Heald & Kevin Zbuk

  2. JM Hilden is the Chair of the Department of Pediatric Hematology/Oncology and Medical Director of Pediatric Palliative Medicine at the Cleveland Clinic and a Principal Investigator at the US Children's Oncology Group (COG). A Norton is a trainee Pediatric Hematologist and Researcher, and P Vyas is a Group Leader at the MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, and a Consultant Hematologist at the John Radcliffe Hospital, Oxford, UK.,

    Joanne M Hilden, Alice Norton & Paresh Vyas

  3. and Professor and Vice Chairman of the Department of Genetics at Case Western Reserve University School of Medicine, KS Theil is Professor of Pathology at the Cleveland Clinic Lerner College of Medicine and a Staff Hematopathologist at the Cleveland Clinic, and C Eng is Chair and Founding Director of the Genomic Medicine Institute, the Founding Director of the Center for Personalized Genetic Healthcare, all at the Cleveland Clinic, Professor of Molecular Medicine at the Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA.,

    Karl S Theil & Charis Eng

Authors
  1. Brandie Heald
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  2. Joanne M Hilden
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  4. Alice Norton
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  7. Charis Eng
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Correspondence to Charis Eng.

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The authors declare no competing financial interests.

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Heald, B., Hilden, J., Zbuk, K. et al. Severe TMD/AMKL with GATA1 mutation in a stillborn fetus with Down syndrome. Nat Rev Clin Oncol 4, 433–438 (2007). https://doi.org/10.1038/ncponc0876

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