Here, we focused on rare early onset developmental disorders with loss-of-function (LoF) pathogenic variations in DNMT3A (Tatton-Brown-Rahman syndrome; TBRS) [33] and in DNMT3B (Immunodeficiency Centromeric instability and Facial dysmorphism; ICF) [34]. This evidence concerns the gene DNMT3B and Tatton-Brown-Rahman overgrowth syndrome.