A recent study including individuals with pathogenic variants of the TRIO gene highlighted a good genotype–phenotype correlation: missense mutations in the RAC1-activating GEF domain cause mild intellectual disability and microcephaly, missense mutations in the seventh spectrin repeat at the N-terminus underlie a phenotype characterized by severe intellectual disability and macrocephaly, while non-sense mutations in the TRIO sequence give rise to a more variable phenotype; interestingly, 31% of patients with pathogenic variants of the TRIO gene showed autistic traits [45]. Here, RAC1 is linked to Macrocephaly.