Abstract Background Loeys–Dietz syndrome (LDS) is a rare autosomal dominant genetic disorder of connective tissue, characterised by a broad spectrum of craniofacial, vascular (arterial tortuosity and aneurysms) and skeletal clinical signs. Four subtypes have been described, related to mutations in genes encoding for components of the transforming growth factor beta signalling pathway (TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2 and TGFB3). Diagnosis is based on the evaluation of clinical manifestations and family history. Therefore, many radiologists remain unfamiliar with the imaging and clinical findings in LDS. The Case 75–year–old woman, history of surgery for ruptured gastric a. aneurysm and ectasia of visceral arterial vessels. One year onset of worsening dyspnoea and asthenia, at echocardiography (ECOCG) severe aortic insufficiency has been detected and patient underwent aortic valve replacement with bioprosthesis. Cardiac surgery was complicated by aortic dissection (Stanford A; DeBakey I type) treated with replacement of ascending aorta and anterior hemiarch with tubular prosthesis. On that occasion a family diagnosis of SMAD3 gene mutation was made (both sister and nephew typed), compatible with Loeys–Dietz syndrome type 3. At the control angioTC evidence of proximal and distal anastomosis in order, in the absence of signs of periprosthetic leak. At ECOCG (FE 55%), thickened septum with marked postcardiac dyskinesia. No abnormality detected on ECG. Due to persistence of dyspnoea on mild exertion (NYHA class III) and reduced tolerance to orthostatism, cardiac rehabilitation program was undertaken on an outpatient basis for three months, providing an improvement in exertion tolerance (NYHA II) and a benefit on functional autonomy. LDS is a multisystem connective tissue disorder that is associated with a high burden of complications, a correct diagnosis will allow clinicians to appropriately establish the best therapeutic strategy, especially in cardiac surgery, taking into account the intraoperative and perioperative potential risks.