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Carriers of a constitutional Robertsonian translocation that involves chromosomes 15 and 21 and carriers of constitutional ring chromosome 21 are specifically and highly predisposed to developing intrachromosomal amplification of chromosome 21 (iAMP21) ALL.[24,25] Down syndrome Children with Down syndrome have an increased risk of developing both ALL and AML,[26-28] with a cumulative risk of developing leukemia of approximately 2.1% by age 5 years and 2.7% by age 30 years.[26,28] These rates represent a 20- to 30-fold increased risk of ALL and over 100-fold increased risk of AML for children with Down syndrome.[27,28] A genome-wide association study found that four susceptibility loci associated with B-ALL in the non-Down syndrome population ( IKZF1 , CDKN2A , ARID5B , and GATA3 ) were also associated with susceptibility to ALL in children with Down syndrome.[29] CDKN2A risk allele penetrance appeared to be higher for children with Down syndrome
