Longitudinal Rett syndrome behaviour questionnaire scores and their associations with genotype and trajectories of mobility, weight and seizure frequency status

The Rett Syndrome Behaviour Questionnaire (RSBQ) describes behavioural and emotional features. This study investigated total RSBQ score trajectories and their clustering, and for trajectory groups, relationships with genotype and mobility, weight-for-age z scores, and seizure frequency. Females in the Australian Rett Syndrome Database who were genetically confirmed with RSBQ data collected between 2000 and 2019 were included. The age trend was modelled with mixed-effects linear regression. Unique trajectory classes for total RSBQ scores and time-varying predictors (mobility, weight-for-age z scores, seizure frequency) were identified with group-based trajectory modelling. Associations between genotype, time-varying predictors and RSBQ total score class memberships were assessed with multinomial logistic regression. There were 1,034 questionnaires collected from 298 individuals (age range 1.7-37.9 years) with a median of 3 (range 1-7) per person. For individuals aged 5 to 20 years at first RSBQ response, the mean (95% CI) scores were 43.9 (40.7, 47.1) at age 5 and 42.0 (39.9, 44.2) at age 20. Total score trajectories clustered into low and middle groups where scores decreased steadily, and a high group which decreased after age 20. Compared to independent walking, assisted walking increased the probability of being in the high-scoring RSBQ group. Very low weight (<-6 z score) increased the probability of being in the medium or high-scoring group. Weak associations were found with seizure frequency and genotype. RSBQ total scores declined with increasing age suggesting improvement in the behavioural and emotional phenotype with age and time. There were few relationships between RSBQ scores and indicators of clinical severity. These natural history data form a baseline for comparison as new treatments become available.