AbstractIn this case report, we present 31-year-old twin sisters diagnosed with severe Barlow mitral valve prolapse, mitral annular disjunction and presence of lateral mid-wall fibrosis diagnosed on MRI as well as ventricular arrhythmias, and a very rare variant of Loeys-Dietz syndrome, being referred to our center for surgical repair. Genetic testing detected pathogenic variants of clinical significance in SMAD3 and KCNH2 genes that are associated with autosomal dominant disease of Loeys-Dietz syndrome. Due to the presence of severe mitral valve regurgitation, the first patient was referred for minimally invasive mitral valve repair that was performed successfully. Before discharge, a subcutaneous ICD implantation was performed as primary prevention against malignant ventricular arrhythmias and sudden cardiac death. Her twin sister presented with the identical diagnosis and underwent the same surgical procedure with S-ICD implantation a few months later.