Prader-Willi Syndrome: The Disease that Opened up Epigenomic-Based Preemptive Medicine

Prader-Willi syndrome (PWS) is a congenital neurodevelopmental disorder caused by loss of function of paternally expressed genes on chromosome 15 due to paternal deletion of 15q11-q13, maternal uniparental disomy for chromosome 15, or an imprinting mutation. We previously developed a DNA methylation-based PCR assay to identify each of these three genetic causes of PWS. The assay enables straightforward and rapid diagnosis during infancy and therefore allows early intervention such as nutritional management, physical therapy, or growth hormone treatment to prevent PWS patients from complications such as obesity and type 2 diabetes. It is known that various environmental factors induce epigenomic changes during the perinatal period, which increase the risk of adult diseases such as type 2 diabetes and intellectual disabilities. Therefore, a similar preemptive approach as used in PWS would also be applicable to acquired disorders and would make use of environmentally-introduced "epigenomic signatures" to aid development of early intervention strategies that take advantage of "epigenomic reversibility".