PIK3CD and Down syndrome: Activated phosphoinositide 3-kinase δ syndrome (APDS) is an inherited primary immunodeficiency due to heterozygous gain of function mutations (GOF) in PIK3CD, which encodes the catalytic subunit p110δ of phosphoinositide 3-kinase δ (PI3Kδ), or heterozygous loss of function mutations in PIK3RI, which encodes the regulatory subunit p85.