PIK3CD and Down syndrome: In addition to immunodeficiency and increased propensity to develop lymphomas and other malignancies, patients with defects in NHEJ can exhibit developmental delay (short stature, microcephaly).47 A germline heterozygous splice site mutation in PIK3R1 leads, like PIK3CD mutations, to an activated PI3Kδ syndrome (APDS) designated PASLI, which stands for p110δ-activating mutations causing senescent T cells, lymphadenopathy and immunodeficiency.49, 50 Depending on the underlying genetic defect, PASLI-CD/APDS1 and PASLI-R1/APDS2 are discerned.