OBJECTIVES: The Rett Syndrome Behavior Questionnaire (RSBQ) was developed to characterize behavioral symptoms in Rett syndrome (RTT). Its use has expanded to measurement of outcomes in clinical trials for RTT. This study investigated relationships between genotype, age, walking ability, sleep and RSBQ scores in RTT.

METHODS: Participants in the International Rett Syndrome Database, InterRett, were recruited for this study. Independent variables included genotype, age-group, functional abilities (walking) and sleep (Sleep Disturbance Scale for Children; insomnia and excessive daytime sleepiness subscales). Their relationships with RSBQ total and general mood and fear/anxiety subscale scores were estimated with multivariate linear regression.

RESULTS: The median age of 210 individuals with RTT was 18y2m (range 6-51 years). Approximately one third could walk independently, and insomnia and sleepiness scores indicated dysfunction in 26% and 18%, respectively. Total, mood, and fear/anxiety scores were decreased (less severity) in teenagers and adults but increased (greater severity) with insomnia and excessive daytime sleepiness. Compared to being unable to walk, assisted walking was associated with higher total and fear/anxiety scores whereas independent walking was associated with higher mood scores. There were few relationships with genotype except compared with the p.Arg270* mutation, individuals with the p.Arg294* mutation had higher fear/anxiety scores (coeff 1.6, 95% CI: 0.00, 3.10).

CONCLUSIONS: RSBQ scores were lower in teenagers and adults and individuals with some walking abilities, suggesting that the RSBQ may not reflect clinical severity. Behaviors were aggravated by sleep difficulties. Genotype results were consistent with literature indicating that the p.Arg294* mutation has implications for mental health.