Longitudinal investigations with larger samples of patients with CdLS-causing gene variants (e.g., inclusion of those with pathogenic variants in HDAC8, SMC3, etc.), comparison groups of idiopathic autism spectrum disorder and/or intellectual disability, and other clinical groups with overlapping CdLS-like features, such as pathogenic variants in EP300, AFF4, NAA10, and TAF6, are necessary to disentangle the different disease pathways that underline the CdLS neurobehavioral phenotype. Here, AFF4 is linked to autism spectrum disorder.