The finding of mutations in transcriptional regulators (ANKRD11, AFF4, ARID1B, BRD4, EP300, and SETD5, among others) in patients with CdLS-like features adds to the mounting evidence that supports the idea that CdLS is caused by defects in transcription (Fig. 4A; Izumi et al. 2015; Parenti and Kaiser 2021). Here, AFF4 is linked to Cornelia de Lange syndrome.