Adult phenotype of Russell-Silver syndrome: A molecular support for Barker-Brenner's theory

Abstract

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.