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

Children with Down syndrome who develop transient myeloproliferative disorder or acute megakaryoblastic leukemia harbor somatic mutations in theGATA1 gene, a phenomenon specific to this syndrome. Heald and colleagues report the first case of a stillborn fetus with Down syndrome-associated acute megakaryoblastic leukemia/transient myeloproliferative disorder and a GATA1mutation. The authors discuss the management of fetuses with suspected or confirmed diagnosis of Down syndrome and highlight the need for genetic screening and counseling based on maternal age. 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.