Abstract The behavioural phenotype of 30 fragile-X, 35 Prader-Willi and 35 Williams-Beuren syndrome children was explored using a psychometric approach. Results confirmed some distinct behaviours as syndrome-specific, but revealed a high degree of within-syndrome variability and overlap between syndromes as well. Parental stress was high in each of the groups, but was mediated by maternal dissatisfaction with family relationships. A multimethod approach with detailed syndrome-specific observations is recommended for further research.