The differential diagnosis of LIG4 deficiency includes Nijmegen Breakage Syndrome (NBS), RAD50 and NHEJ1 deficiencies; Fanconi anemia, and any other congenital disease presenting with: microcephaly, facial dysmorphisms (described as bird-like facies); hypogammaglobulinemia, and low B-cells; including IKAROS and NFKB2 deficiencies. Here, RAD50 is linked to microcephaly.