Although mutations in RB1 are often considered necessary for retinoblastoma initiation, the transition into retinoblastoma may require further changes in key genes, such as KIF14, E2F3, MYCN, DDX1, MDM4, OTX2, DEK, CDH1, BCOR and RBL2 [2]. The gene discussed is MDM4; the disease is retinoblastoma.