Additional research will also be required to elucidate the interplay between hyperactive IFN signaling in DS with other important factors encoded on chr21 (e.g. DYRK1A, APP) (Malinge et al., 2012; Wiseman et al., 2015) or elsewhere in the genome, that have been involved in the development of the specific comorbidities. This evidence concerns the gene APP and Dravet syndrome.