Significance Anemia is the predominant clinical manifestation of myelodysplastic syndromes (MDS). Genes that are aberrantly expressed and/or mutated that lead to the dysplastic erythroid morphology seen in −7/del(7q) MDS have not been identified. In this study, we show that reduced expression of dedicator of cytokinesis 4 ( DOCK4 ) causes dysplasia by disrupting the actin cytoskeleton in developing red blood cells. In addition, our identification of the molecular pathway that leads to morphological defects in this type of MDS provides potential therapeutic targets downstream of DOCK4 that can be exploited to reverse the dysplasia in the erythroid lineage. Furthermore, we developed a novel single-cell multispectral flow cytometry assay for evaluation of disrupted F-actin filaments, which can be used for potential early detection of dysplastic cells in MDS.