Development of quantitative EEG biomarkers for Smith Magenis syndrome

ABSTRACT Smith-Magenis syndrome (SMS) is a neurodevelopmental disorder caused by either deletion of 17p11.2 or mutations resulting in haploinsufficiency of the RAI1 gene located on 17p11.2. Common features of SMS include cognitive impairment, motor delays, impaired speech/language, a characteristic behavioral profile, and severe sleep disruptions. Recent preclinical studies have identified potential targets for therapeutic intervention in SMS. The central goal of our work is to facilitate future clinical trials by defining quantitative EEG biomarkers for SMS. Prior work has observed qualitative impairments in ~50-60% of SMS EEGs; this will be the first quantitative study of SMS EEGs. We will retrospectively analyze overnight EEGs containing periods of wake and sleep from children with SMS and age and sex-matched neurotypical controls. Using spectral analyses and other quantitative methods, we will complete two Aims: (1) Test the hypothesis that low-frequency brain rhythms are enhanced in SMS, and (2) test the hypothesis that sleep spindles are disrupted in SMS. This work will determine whether quantitative EEG analysis can detect SMS biomarkers that may then be validated prospectively prior to deploying in future clinical trial settings.