Auditory Evoked Potentials Differ from Controls and Correlate with Aspects of Cognition in Kabuki Syndrome and Rubinstein-Taybi Syndrome

Abstract

Objective Kabuki syndrome (KS) and Rubinstein-Taybi syndrome (RSTS) are two disorders caused by dysfunctional components of the epigenetic machinery and both result in intellectual disability. Mouse models of both KS and RSTS have seen reversal of cognitive impairment with epigenetic treatments. However, a great need exists for biomarkers in these disorders to improve the likelihood of successful clinical trials. This study aimed to investigate cortical auditory evoked potentials (AEPs) in KS and RSTS so that it could potentially be developed into a response biomarker in the future. Methods The amplitude of the N1-P2-N2 complex was measured for passive listening to monotonal auditory stimuli in individuals with KS, with RSTS, and typically developing controls. A standardized cognitive assessment battery was performed and specific subtests were correlated with AEP values. Results Groups differed significantly in P2, N2, and P2-N2 amplitude although RSTS was consistently more different from typically developing controls than was KS. The mid- to late-phase AEP components (P2 and N2) also correlate with cognition within and across these groups particularly with language whereas earlier components N1 and P2 correlate more with measures of executive functioning. Conclusion Late-phase components of AEPs differ in KS and RSTS from each other and from controls. KS and RSTS differ from controls in P2 and N2 amplitude in the same direction and both show a positive correlation between language and P2 amplitude and a negative correlation between language and N2 amplitude. Together they also show an association with N1 and P2 amplitude and executive functioning. Significance AEPs may turn out to be a valuable response biomarker in KS and RSTS individually and together.