Comprehensive molecular analysis in a cohort of 716 probands with CdLS revealed that causative variants in genes such as AFF4, ANKRD11, ARCN1, ARID1B, ASXL2, and others account for a significant proportion of etiologies beyond the traditional CdLS genes (25% of probands) [7]. This evidence concerns the gene AFF4 and Cornelia de Lange syndrome.