Transient myeloproliferative disorder in children with Down syndrome: clarity to this enigmatic disorder

Summary Children with trisomy 21 have a unique predisposition to develop a megakaryoblastic proliferative disease of varying severity during their first 3 months of life. This disorder exists in no other children or adults without the presence of trisomy 21 and only occurs in the fetal or neonatal period of life. Its spontaneous resolution in most cases further delineates it from otherwise indistinguishable neonatal leukaemias. The identification that GATA1 mutations are the leukaemogenic source along with three recently reported prospective clinical trials now provide a clearer understanding of this haematopoietic disorder. These recent advances in this enigmatic disorder, now known as Transient Myeloproliferative Disorder, are reviewed here in order to bring clarity to the breadth of organ involvement, the range of severity, the risk factors for mortality, the therapeutic options for severe manifestations, the natural course of spontaneous resolution regardless of therapy, and the elucidation of the subsequent risk for myeloid leukaemia.