A specific hypermethylation signature associated with LoF variants in the SETD1B gene was recently demonstrated (Hunter 2005), with profiles overlapping those of patients affected by Hunter–McAlpine syndrome, who harbor duplication of NSD1. Indeed, NSD1, which also contains a SET domain, is responsible for Sotos1 syndrome mainly but not only in presence of frameshift and nonsense variants (https://varsome.com/gene/NSD1; Türkmen 2003; Laccetta 2017). This evidence concerns the gene SETD1B and Hunter-McAlpine craniosynostosis.