The need for tailoring medical treatments to the patient is because the course and manifestations of diseases, as well as the responses to treatment, often differ significantly between individuals. Those differences are, to a large extent, genetically and epigenetically determined. The study attempts to delineate the genetic basis for clinical disease variations in the context of single-gene skin diseases. The characterization of factors modulating clinical behavior will lead to the identification of novel biomarkers, actionable drug targets, and innovative therapeutic strategies to improve disease management of simple and complex traits alike.