The direction of treatment for imprinting disorders: A focus on Prader-Willi and Angelman Syndrome

Imprinting Disorders are a group of congenital pathologies that arise from defects in epigenetic programming or genomic imprinting. Treatments of these disorders today are based primarily on symptomatic management indicating a need for further research into potential epigenetic therapies. There is a lack of focus into worthwhile permanent solutions for these disorders. In this review, we discuss the role of imprinting in congenital defects and use Prader-Willi and Angelman syndrome as examples of imprinting disorders to show the imprinting mechanisms that lead to their phenotypic expression, their clinical manifestations, the importance and impact that early identification has, and the current standard of care. Recent research exploring epigenetic and gene-targeted therapies for imprinting disorders have shown promise as future routes to chromosomally targeted therapies for patients impacted by imprinting disorders. Topoisomerase inhibitors are an area of interest and were found to induce expression in a clinically silent gene in Angelman syndrome. Histone methyltransferase (G9a) inhibitors are another potential epigenetic therapy for Prader-Willi Syndrome as a way to induce expression of silenced genes on the maternal allele. Additionally, the use of an adeno-associated virus as a vector for delivery of DNA sequences has shown promise in patients with spinal muscular atrophy and could prove to be effective in the treatment of imprinting disorders. These new avenues of potential care are promising targets for future research that have the potential to lay the foundation for novel gene-targeted therapies.

Keywords: #Angelman; #Genetics; #Imprinting; #MedicalGenetics; #MedicalTreatment; #Prader-Willi