The IEI categories with higher number of immunological manifestations in utero or in perinatal period are: (i) diseases of immune dysregulation (HLH, IPEX and other Tregopathies, autosomal recessive ALPS with complete lack of FAS protein expression) and (ii) autoinflammatory diseases (NOMID/CINCA, DIRA and some interferonopathies, such as Aicardi-Goutières syndrome, AGS, and USP18 deficiency). The gene discussed is USP18; the disease is immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome.