Skin involvement in Down syndrome transient ... - Wiley Online Library

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Mar 3, 2012 - blasts. Constitutional trisomy 21 was confirmed by karyotyping ... her bone marrow showed no excess of blasts and her liver ... E-mail: Owen.
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Skin involvement in Down syndrome transient abnormal myelopoiesis

A new-born baby girl with phenotypic features of Down syndrome presented with hepatosplenomegaly and a haemoglobin concentration (Hb) of 146 g/l, platelet count 73 9 109/l and white blood cell (WBC) count 39·1 9 109/l. Blood cytomorphology and immunophenotyping showed 50% circulating blasts. Constitutional trisomy 21 was confirmed by karyotyping and a diagnosis of transient abnormal myelopoiesis (TAM) associated with Down syndrome was made. GATA1 mutation screening using WAVE® and direct sequencing of polymerase chain reaction products failed to show any of the known common mutations. During hospitalization she developed a generalized papular skin rash, the histology of which showed a superficial perivascular infiltrate of predominantly mononuclear cells with round to reniform nuclei and variable quantities of pale cytoplasm. No mitotic figures were identified but there was conspicuous apoptosis. Immunohistochemical stains were strongly positive for CD117 in the perivascular cell population, which showed patchy CD68 positivity. CD34, CD3, CD7, CD56, CD61 and toluidine blue stain were negative. The morphological and immunophenotypic features were consistent with involvement of skin by TAM. During follow up, she became progressively pancytopenic with her Hb dropping to 60 g/l and her platelet count falling to 20 9 109/l, requiring First published online 3 March 2012 doi: 10.1111/j.1365-2141.2012.09079.x

supportive transfusion. By the second month of life she continued to be thrombocytopenic, but her WBC count normalized, her bone marrow showed no excess of blasts and her liver returned to normal size. Her skin rash subsided over the same time period with no specific intervention. In the third month of life she developed rapidly progressive hepatic dysfunction and subsequently died despite intensive management. Limited post mortem examination showed no evidence of TAM in the liver but identified extensive hepatocellular necrosis including bridging necrosis and venoocclusive disease – features previously reported in TAM. Skin involvement in TAM is rare, as is the absence of a detectable mutation in haematopoietic gene GATA1. The failure in this case to detect a mutation in GATA1, especially with the high blast count at presentation, suggests an uncommon mutation may have been driving the TAM and be responsible for the atypical phenotype. Janusz Krawczyk1 Michael McDermott2 Alan D. Irvine3

Aengus O’Marcaigh1 Lorna Storey1 Owen Smith1

1

Departments of Haematology, 2Pathology and 3Dermatology Our

Lady’s Children’s Hospital, Crumlin, Dublin, Ireland E-mail: [email protected] ª 2012 Blackwell Publishing Ltd, British Journal of Haematology, 2012, 157, 280