Why do some institutionalized children develop indiscriminate behavior (IB) while others do not? Considering children with Williams syndrome (WS) may provide an answer because IB has been observed routinely among individuals with this rare genetic neurodevelopmental disorder. By conceiving WS as a natural genetic model that mimics the indiscriminate phenotype and, more importantly, is associated with the deletion of genes in a specific region, we propose an integrative conceptual framework that underscores the dynamic developmental interplay between genes, endophenotypes, and environment. In this article, we consider the etiology of IB among institutionalized children, which emphasizes environmental factors, followed by the effect of such behavior on WS children's hypersociability, which highlights the crosstalk between genes and neuropsychological features in programming their distinctive social‐emotional and behavioral phenotype. We propose new hypotheses regarding the etiopathogeny of IBs in institutionalized children, particularly the prediction of specific Gene × Environment interactions.