The occurrence and co-occurrence of psychiatric disorders have been more frequently reported in people with Intellectual Disability (ID) than in the general population. The present study was aimed at verifying whether the psychiatric profile of individuals with ID is just a consequence of ID or derives from a specific genotype. The psychiatric profile of 112 individuals with Down syndrome (DS) and 85 with Williams syndrome (WS) was examined. The interactions between psychiatric symptom clusters and the effect of age were also investigated.Participants with WS had higher rates of psychiatric disorders, and, specifically, of Anxiety disorders and Psychosis than DS. However, the psychiatric profile changed by age, since Anxiety disorder was higher in individuals with WS compared to DS in young age, while Psychosis in old age. A relation between the occurrence of disorders, as Anxiety disorder and Mood Disorder, was found only in participants with WS. Moreover, distinct Anxiety and Behavior Disorder subtypes emerged between groups.Results indicate that the genetic etiology of ID differently affects the psychiatric characteristics of the groups and suggest the importance of a targeted psychiatric care for individuals with WS and DS.