Using transcriptome analysis of a large human cohort study, we observed that overexpression of few select HSA21 genes correlates with signatures of IFN hyperactivity and inflammation, including the four IFNRs. Although hyperactive IFN signaling has been noted in cells with trisomy 21 since the 1970s, its contribution to systemic phenotypes of DS in vivo has not been defined9. The gene discussed is IFNA1; the disease is Dravet syndrome.