This master dissertation will try to tackle two important clinical problems related to Marfan Syndrome (MFS). The first part deals with the presence of variants of unknown significance (VUS). Patients presenting with a VUS cannot be diagnosed correctly. For patients this leads to a lot of uncertainty and for clinicians it is hard to determine the correct follow-up and therapy for these patients. By creating an in vivo model in which patient-specific variants can be tested, we can determine the pathogenicity of this specific variant. This could allow better identification and follow-up of patients at risk and reduce uncertainty. Marfan syndrome (MFS) presents phenotypically with a lot of variability. Identifying the FBN1 variant in a patient does not always provide clarity about the severity of the disease. Determining the mechanisms and genes involved in this variability could help to identify patients with a higher risk for aneurysms and dissections. Identifying potential modifier genes involved in these mechanisms could provide more clarity in the diagnosis of patients and the correct follow-up. This will be the main focus of the second part of this master dissertation.