Developmental Origins of Health and Disease theory stems from large‐scale epidemiologic observation. The presumed mechanism for this hypothesis includes epigenetic changes; however, it remains to be elucidated if individuals with intrauterine growth retardation and epigenetic changes confirmed at the molecular level are indeed susceptible to adult‐onset disease. Here we document three individuals with Russell‐Silver syndrome, a prototypic condition caused by hypomethylation of the differently methylated imprinting center region 1 (ICR1) between the IGF2 and H19 loci on chromosome 11p15. At follow‐up, the three patients developed adult‐onset diseases such as obesity, hypertension, and diabetes mellitus in their early 20s. The presence of molecularly confirmed epigenetic changes in these patients provides a biological basis for Barker‐Brenner's theory at an individual level.