The Genetic Etiology Of Dupuytren’s Disease: exploring susceptibility, profiling risk, and predicting recurrence

The studies of this thesis focus on Dupuytren’s disease, a disorder characterized by proliferation of the connective tissue of the palms of the hands. In this disease, nodules and cords appear, that can cause a permanent contractures of the fingers. Although a contracture can be ameliorated with surgery (among others), over time it often returns. The causes of the development of this disease and its recurrence after treatment are largely unknown. Since Dupuytren’s disease often occurs within families, it is known to have a strong heritable (genetic) basis. In the research of this thesis we studied different aspects of heritability of Dupuytren’s disease. We showed that genetic factors explain a large part of the differences in disease prevalence between different ethnic populations and identified new genetic factors that increase the risk of Dupuytren’s disease. We zoomed in on which of these factors are likely to play major roles and studied the mechanism of action of a potential drug for Dupuytren’s disease. Furthermore, each person has a unique constitution (profile) of genetic risk factors. We therefore also studied whether patients’ genetic risk profiles have a predictive value of risk of recurrence after treatment. Although the predictive value of genetic risk profiling for Dupuytren’s disease recurrence after treatment at this time is insufficient for integration in patient care, we established that the genetic susceptibility of patients for Dupuytren’s disease can indeed help to predict risk for recurrence after treatment.