Which hematologic disorders are associated with Down syndrome?

Updated: May 18, 2020
  • Author: Gratias Tom Mundakel, MBBS, DCH; Chief Editor: Maria Descartes, MD  more...
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The most important hematologic abnormality in Down syndrome involves the white blood cells. Children with Down syndrome have an increased risk of developing leukemias, including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). [40] AML is as common as ALL in these individuals. Acute megakaryocytic leukemia is the most common form of AML in affected children and is uncommon in children who do not have Down syndrome.

The relative risk of acute leukemia in the first 5 years of life is 56 times that of individuals without Down syndrome. Approximately one in 150 patients develops leukemia. (Neonatal leukemoid reactions [ie, pseudoleukemia] are common, and distinguishing these from true leukemia frequently poses a diagnostic challenge.) [41]

Approximately 10% of newborns with Down syndrome develop a preleukemic clone, originating from myeloid progenitors in the fetal liver that are characterized by a somatic mutation in GATA1, which is localized on the X-chromosome. Mutations in this transcription factor lead to a truncated mutant protein, GATA1short or GATA1s. [42, 43]  This preleukemia is referred to as transient leukemia (TL), transient myeloproliferative disease (TMD), or transient abnormal myelopoiesis (TAM). [44, 45, 46]

TMD is a hematologic abnormality that primarily affects infants with Down syndrome in the neonatal period. [47, 48] It is characterized by an excessive proliferation of myeloblast cells in the infant’s blood and bone marrow. [49]

An estimated 25% of infants with Down syndrome who present with TMD develop megakaryocytic leukemia 1-3 years later. [50] TMD is associated with pancytopenia, hepatosplenomegaly, and circulating immature white blood cells (WBCs). TMD spontaneously regresses within the first 3 months of life. In some children, however, it can be life-threatening. [51, 52]

Although the risk for leukemia is higher in children with Down syndrome, this risk normalizes by the age of 20 years. By age 30 years, the risk of developing leukemia is 2.7%. On the other hand, the risk of developing most solid tumors, such as cervical, lung, and prostate cancer, is lower; however, there is an increased risk for ovarian and testicular germ cell tumors and, perhaps, retinoblastomas and lymphomas. [53, 54, 55]

Another hematologic abnormality, polycythemia, is common in the newborn period.

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