The prevalence of organ-specific phenotypes (e.g., cutaneous phenotypes in NLRP1-associated syndromes [149,150]) or cytokine-driven diseases (IL-18 in NLRC4-associated syndromes [151] compared to IL-1 in NLRP3/Cryopyrin-Associated periodic Syndromes [152]) may be largely due to differential transcriptional regulations. Here, IL1A is linked to Down syndrome.