cognitive impairment, mouse models, GTF2I, GTF2IRD1, CLIP2, LIMK1, NCF1, EIF4H, STX1A/B, FZD9, HIP1, CLDN3, FKBP6, organoid, induced pluripotent stem cell (iPSC) and forebrain organoids.<h4>Results</h4>Mouse models including multigene deletion strains recapitulating the WS critical region and single-gene knockout strains targeting Gtf2i, Gtf2ird1, Clip2 and Limk1 replicate key WS neurodevelopmental phenotypes, substantially contributing to mechanistic studies and therapeutic screening. This evidence concerns the gene GTF2IRD1 and Cognitive impairment.