PIK3CD and Down syndrome: Activated phosphoinositide 3-kinase-δ syndrome (APDS) results from either gain-of-function mutations in PIK3CD encoding the catalytic subunit p110δ (APDS1), or by loss-of-function variants in PIK3R1 encoding the regulatory subunits p85α, p55α, or p50α (APDS2) (165).