Psychopathology is prevalent in Williams (WS), fragile X (FXS) and Prader-Willi (PWS) syndromes. However, little is known about the potential correlates of psychopathology in these groups. A questionnaire study was completed by 111 caregivers of individuals with WS (n = 35); FXS (n = 50) and PWS (n = 26). Mean age was 26 years (range 12-57 years); 74 (67%) were male. Multiple regression analyses indicated that higher rates of health problems and sensory impairments predicted higher psychopathology in WS (p < 0.0001). In PWS, poorer adaptive ability predicted higher overall psychiatric disturbance (p = 0.001), generalised anxiety (p = 0.006) and hyperactivity (p = 0.003). There were no significant predictors in FXS. This study highlights dissociations in the potential risk markers of psychopathology between genetic syndromes. Implications for intervention are discussed.