This clinical case series, for the first time in PWS, describes the clinical significance of the most commonly studied pharmacodynamic genes and their polymorphisms: serotonin transporter (SLC6A4), serotonin 2A receptor (HRT2A), serotonin 2C receptor (HRT2C), catechol-o-methyltransferase (COMT), adrenergic receptor 2A (ADRA2A), methylene tetrahydrofolate reductase (MTHFR), and human leucocytic antigens (HLA-A and B). This evidence concerns the gene COMT and Prader-Willi syndrome.