An interferon signature is also recognised in SLE [9] and in monogenic disease in association with mutations in TMEM173 [10] and ISG15 [11] and any of the phenotypes recognised with mutations in TREX1, RNASEH2A/B/C, SAMHD1, ADAR1 and IFIH1 - including the monogenic encephalopathy Aicardi-Goutières syndrome (AGS), which can show significant overlap with SPENCD [12, 13]. This evidence concerns the gene ISG15 and Spondyloenchondrodysplasia with immune dysregulation.