Three examples of tools assisting diagnosis-making are the Hyper-IgE syndrome (HIES) score, which was originally designed for autosomal dominant STAT3-LOF syndrome [4, 5], and the ‘diagnostic guidelines’ and the ‘H score’ used for primary and secondary hemophagocytic lymphohistiocytosis (HLH), respectively [6–8] (Table 1). The gene discussed is STAT3; the disease is hemophagocytic syndrome.