This clinical case series, for the first time, describes the distribution and frequency of polymorphisms of pharmacodynamic genes (serotonin transporter, serotonin 2A and 2C receptors, catechol-o-methyltransferase, adrenergic receptor 2A, methylene tetrahydrofolate reductase, and human leucocytic antigens) across the two major molecular classes of PWS in a cohort of 33 referred patients who met medical criteria for testing. Here, COMT is linked to Prader-Willi syndrome.