TP53 and Down syndrome: Germinal gene mutations: ACC can arise in the context of cancer-predisposing syndromes (Li-Fraumeni [TP53], Lynch [NMR genes], Beckwith-Wiedemann [CDKN1C, H19, IGF2, KCNQ1OT1], Carney complex [PRKAR1A], Multiple Endocrine Neoplasia type 1 [MEN1] syndromes) with hereditable genetic lesions of the germinal line in approximately 10% and 50–80% of adult and pediatric cases, respectively [13–15].