Development of a Cognitive Assessment Battery for Adolescents and Adults with Kabuki Syndrome Type 1

Background Kabuki syndrome type 1 (KS1) is a rare genetic neurodevelopmental disability syndrome characterized by significant weaknesses in visuospatial cognitive processes in comparison to other cognitive domains. There is a great unmet need for validated and specific cognitive outcome measures for clinical trials in patients with KS1. This study evaluated the validity and reliability of a Kabuki Syndrome Cognitive Assessment Battery (KS-CAB), a visuospatial assessment that is specific to KS1. Twenty-two individuals with molecularly confirmed KS1 (mean age = 21.1 years, range = 12.5–36.1 years) completed the same cognitive battery on two separate days. Results Individuals with KS1 demonstrated consistent deficits in visuospatial cognition domains (often > 3 standard deviations below the mean), whereas other cognitive domains, such as language and executive functioning, were more variable. All visuospatial measures comprising the KS-CAB exhibited high test–retest reliability (Cronbach’s alpha = 0.81–0.97; intraclass correlation coefficient = 0.71–0.94). Subgroup analyses revealed that participants with missense variants outperformed those with truncating variants in visuospatial tasks. Conclusions These findings are consistent with previous literature that visuospatial deficits are prominent in KS individuals and disproportionate to their intelligence quotient (IQ). In addition, this study demonstrated the reliability of 11 visuospatial subtests of existing cognitive measures, suggesting these are good candidates for clinical trial outcome measures in KS1.