Acuna-Hidalgo et al. (2017) identified four individuals carrying SETBP1 variants in close proximity to the canonical mutation hotspot, including p.(Glu862Lys), p.(Ser867Arg), and p.(Thr873Ile), who showed a milder developmental phenotype with clinical characteristics that partially overlapped with classical SGS. Moreover, individuals with variants located further from the mutation hotspot showed a variable clinical phenotype ranging from mild to severe intellectual disability (Leonardi et al., 2020; Wong et al., 2022). This evidence concerns the gene SETBP1 and Intellectual disability.