Pharmacodynamic Gene Testing in Prader-Willi Syndrome.

Janice Forster,Merlin G Butler,Jessica Duis

doi:10.3389/fgene.2020.579609

Abstract

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-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. 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.

Highlights

Pharmacogenomics is the study of how structural gene changes determine the function, regulation and production of gene products that affect the body’s response to medication
Given the high likelihood of psychiatric co-morbidity in PraderWilli syndrome (PWS) with possible genetic subtype specificity, pharmacodynamic gene testing may be considered as an additional tool to inform psychotropic medication management
When the results of pharmacodynamic testing for our cohort of 33 patients are pooled without regard to PWS genetic subtype, the distribution of most of the pharmacodynamic polymorphisms is comparable to population norms

Summary

Introduction

Pharmacogenomics is the study of how structural gene changes determine the function, regulation and production of gene products that affect the body’s response to medication. Pharmacodynamic testing involves the assessment of genes that code for neurotransmitter receptors and transporters, antigens, and enzymes that have an impact on drug activity and response, usually in the brain, as a function of an individual’s DNA pattern. Pharmacodynamic phenotypes may explain why certain classes of medications are not as effective in some people, beyond that predicted by the knowledge of drug pharmacokinetics and cytochrome P450 genes. Pharmacodynamic phenotypes may inform the risk of occurrence of side effects. Clinicians who are informed about the therapeutic value of pharmacodynamic testing appreciate and utilize this knowledge to evaluate potential side effects and variability of response to certain classes of psychotropic medication. Using psychotropic medication to manage the multifaceted symptoms associated with PraderWilli syndrome (PWS) requires a knowledge of evidence-based science, clinical expertise, and risk for potential side effects. The features of PWS include infantile hypotonia, a poor suck with

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Conclusion