DNMT3A and Tatton-Brown-Rahman overgrowth syndrome: Somatically acquired pathogenic variants in DNMT3A are associated with >20% of acute myeloid leukemia (AML) cases, whereas heterozygous germline pathogenic loss-of-function variants have been found to underlie Tatton-Brown–Rahman syndrome (TBRS; also known as DNMT3A-overgrowth syndrome, OMIM 615879) (Challen et al. 2011; Tatton-Brown et al. 2014).