An infant with Down syndrome develops pallor, petechiae, and hepatosplenomegaly at 2 months of age. Peripheral smear shows blasts that stain positive for myeloperoxidase. Which molecular event, superimposed on trisomy 21, underlies this complication?

• A Somatic mutation of GATA1 in fetal megakaryocyte progenitors ✓
• B Germ line deletion of RB1 on chromosome 13
• C Expansion of a CAG repeat in the RUNX1 gene
• D Constitutional activation of JAK2 by exon 14 deletion

Explanation

Children with trisomy 21 have a markedly increased risk of acute megakaryoblastic leukemia and a preceding self-limited condition called transient abnormal myelopoiesis. Both require trisomy 21 plus acquired somatic mutations in GATA1 within fetal hematopoietic cells. RUNX1 mutations cause familial platelet disorder with AML predisposition, not the Down syndrome leukemia phenotype, which rules out the best distractor.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.