Notable monogenic PIDs, whose genetic background directly predisposes to cancer, include the activated phosphoinositide 3-kinase δ syndrome (APDS), nuclear factor kappa B subunit 1 (NF-κB1) insufficiency, and Signal transducer and activator of transcription 3 (STAT3) gain-of-function syndrome (11–13). The gene discussed is STAT3; the disease is Down syndrome.