Background Individuals with Phelan-McDermid syndrome (PMS) are characterised by phenotypical traits that can be experienced as challenging by their environment. This study assessed parenting stress and Family Quality of Life (FQOL) in parents of individuals with PMS and identified potential contributing variables. Method: Mothers (n = 14) and fathers (n = 13) of individuals with PMS (n = 14; 6 females, 8 males; age 2-37, M = 20, SD = 11.92) completed questionnaires on parenting stress, FQOL, adaptive behaviour and background characteristics. Results: Mothers and fathers experienced high, similar and related levels of parenting stress and FQOL satisfaction. Parenting stress and FQOL satisfaction were inversely related. High and low ratings were retrieved for subscales measuring feelings of parental role restriction and emotional well-being, respectively. The adaptive skills of the individuals with PMS were related to fathers' parenting stress and FQOL satisfaction. Conclusions: Clinical practice is encouraged to be attentive to family dynamics and grasp opportunities to interact with these dynamics.