We describe a proband presenting with an unusual phenotype comprising intellectual disability and progression to severe movement disorder, who was found to harbor a germline de novo essential splice-site variant in CAMK4. We demonstrate that the splicing alteration results in heterozygous expression of CaMKIV with a truncated autoregulatory domain, mimicking in vitro–engineered deletion mutants that have been used for decades in the study of constitutive CaMKIV activation. This evidence concerns the gene CAMK4 and Intellectual disability.