Background: Despite the increasing number of clinical trials involving children with neurodevelopmental disorders, appropriate and objective outcome measures for behavioral symptoms are still required.Aim: This study assessed the agreement between parents' and clinical researchers' ratings of behavioral problem severity in children with fragile X syndrome (FXS) and chromosome 15 imprinting disorders.Methods and Procedures: The cohort comprised 123 children (64% males), aged 3-17 years, with FXS (n = 79), Prader-Willi (PWS; n = 19), Angelman (AS; n = 15), and Chromosome 15q duplication (n = 10) syndromes. Specific items from the Autism Diagnostic Observation ScheduleSecond Edition and Aberrant Behavior Checklist-Community Edition mapping to corresponding behavioral domains were selected ad-hoc, to assess behavioral problems. Outcomes and Results: Inter-rater agreement for the cohort was slight for self-injury (Intraclass Correlation Coefficient (ICC) = 0.12), fair for tantrums/aggression (0.24) and mannerisms/stereotypies (0.25), and moderate for hyperactivity (0.48). When stratified by diagnosis, ICC ranged from poor (0; self-injury, AS and PWS) to substantial (0.48; hyperactivity, females with FXS).Conclusions and Implications: The high level of inter-rater disagreement across most domains suggests that parents' and researchers' assessments led to discrepant appraisal of behavioral problem severity. These findings have implications for treatment targets and outcome measure selection in clinical trials, supporting a multi-informant approach.