Most individuals with DICER1 syndrome have a germline loss-of-function DICER1 mutation with a second tumor-specific missense mutation in the RNase IIIb domain; these tumor-specific RNase IIIb missense mutations usually involve one of five hot spot codons (E1705, S1709, G1809, D1810, and E1813) [208, 210, 232]. The gene discussed is DICER1; the disease is DICER1-related tumor predisposition.