Developmental science integrates concepts from developmental medicine, human genetics, developmental and clinical psychology to understand behavioural adjustment and maladjustment in children, adolescents and adults as a product of the transactions between the child, its biological organization and its social experience. Put into such a biopsychosocial perspective, children with intellectual disabilities in general as well as children with single or multiple gene disorders present challenging examples to examine possible relationships between phenotype, environtype and genotype. To illustrate this approach, first an overview over prevalence and type of mental health problems in children with intellectual disabilities is given and some aspects of their vulnuerability are discussed. Second, the behavioural phenotype of four mental retardation syndromes with well documented and specific behavioural features is described: Fragile-X-syndrome, Williams syndrome, Down syndrome, Cornelia-de-Lange syndrome. Investigations in these groups support the value of analyzing early developmental patterns in combination with neuroimaging approaches in order to promote the understanding of disorders and to design preventive interventions focused on their core features.