Two main syndromes are fundamentally caused by genetic defects that result in T-cell hyperactivation: (i) Immune Dysregulation, Polyendocrinopathy, Enteropathy, and X-linked syndrome (IPEX), caused by mutations in forkhead box P3 (FOXP3) gene, and (ii) Autoimmune Polyendocrinopathy, Candidiasis, and Ectodermal Dystrophy syndrome (APECED), also known as autoimmune polyglandular syndrome type-1 (APS-1), caused by variants in the autoimmune regulator (AIRE) gene [56,57]. Here, AIRE is linked to autoimmune polyendocrinopathy.