Pharmacodynamic Gene Testing in Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is a rare genetic disorder with a complex neurobehavioral phenotype associated with considerable psychiatric co-morbidity. 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--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. When results were pooled across PWS genetic subtypes, genotypic and allelic frequencies did not differ from normative population data. However, when the genetic subtype of PWS was examined, there were differences observed across all genes tested that may affect response to psychotropic medication. Due to small sample size, no statistical significance was found, but results suggest that pharmacodynamic gene testing should be considered before initiating pharmacotherapy in PWS. Larger scale studies are warranted.