Down syndrome is a genetic disorder known to cause many complications with lifelong effects. Patients with Down syndrome are known to produce excess interferon gamma, a major culprit of psoriasis formation and severity. Both conditions increase patient risk for major cardiovascular events; however, a potential association between Down syndrome and severe psoriasis has not been well studied. This article discusses a patient with Down syndrome and worsening plaque psoriasis who died of an acute myocardial infarction.