Background: Parenting stress was investigated in mothers with a child with Angelman syndrome (AS) or Prader-Willi syndrome (PWS), which are genetically related. Method: Mothers of 24 children with AS and 23 children with PWS (2-12 years) completed the Nijmegen Parenting Stress Index-Short, Developmental Behaviour Checklist, and Vineland Screener 0-12. Results: Parenting stress was high for 58% of AS and 26% of PWS cases. For both syndromes, no relationship existed with the child's gender, age, or behavioural problems. In PWS there was no effect on level of functioning. Overall, more mothers with a child with AS perceived high parenting stress. When children showed low levels of behavioural problems this difference was contained. However, when children exhibited severe behavioural problems, parenting stress was the same for both syndromes. Conclusion: In AS professional family support is essential, since parenting is stressful for many mothers. In PWS, this is especially the case when behavioural problems are present. (Contains 3 tables.)