We identified siblings, with erythroderma and exudate in whole body, recurrent skin infection and sepsis and prolonged diarrhoea from the early neonatal period, harbouring compound heterozygous missense variants of ADAM17. Although both affected siblings manifested clinical features of NISBD1, all reported genetic deficiencies of ADAM17 detected in patients with NISBD15–7 and the ClinVar database included alterations causing a complete loss of ADAM17 expression and function (predicted null variants). The gene discussed is ADAM17; the disease is Sepsis.