The development of whole-exome and whole-genome sequencing (WES/WGS) technologies has facilitated the discovery of new genes associated with CS syndromes, such as ERF (CS type 4), TCF12 (CS type 3), and P4HB and SEC24D (Cole–Carpenter types 1 and 2), as well as genes involved in syndromes where CS is a variable feature [e.g., Weiss–Kruszka (ZNF462) and Say–Barber–Biesecker–Young–Simpson (KAT6B) syndromes] (Clayton-Smith et al., 2011; Sharma et al., 2013; Twigg et al., 2013; Garbes et al., 2015; Rauch et al., 2015; Weiss et al., 2017). This evidence concerns the gene TCF12 and Cowden syndrome 1.