While gain-of-function (GoF) mutations in Ctnnb1 are linked to cancers such as liver and colorectal cancer (Harada et al. 1999; Veelen et al. 2011; Singh et al. 2014; Zhang et al. 2021; Loesch et al. 2022; Cai et al. 2024), autosomal de novo loss-of-function mutations can lead to CTNNB1 syndrome, a neurodevelopmental disorder (NDD; Phenotype MIM Number 615075) (Kuechler et al. 2015; Kayumi et al. 2022; Basu et al. 2024). This evidence concerns the gene CTNNB1 and severe intellectual disability-progressive spastic diplegia syndrome.