TRIO and Macrocephaly: Rac1 mutations associated with intellectual disability impair synaptic plasticity (Tian et al., 2018), and variants in the RhoGEF TRIO can cause ASD, intellectual disability, schizophrenia, or macrocephaly, with severe phenotypes predicted by Rac1 overactivation (Katrancha et al., 2017; Sadybekov et al., 2017; Barbosa et al., 2020).