Prader-Willi Syndrome — Changing Proportions of Genetic Subtypes

For many pediatricians, Prader-Willi syndrome (PWS) has served as an introduction to genomic imprinting and epigenetics. Around 1995, it became clear that PWS arises because of the absence of paternally inherited genes in region q11–q13 of chromosome 15. This usually happens through one of two mechanisms: microdeletion of the paternally inherited chromosome or inheritance of two copies of chromosome 15 from the mother and none from the father (maternal uniparental disomy [mUPD]). This form of mUPD typically occurs because the child was conceived with trisomy 15 (which would be a nonviable situation), but one of the copies of chromosome 15 was then lost in a phenomenon known as trisomy rescue. One third of the time, when the trisomy converts…