Novel Mutation of the TGF-β 3 Protein (Loeys-Dietz Type 5) Associated With Aortic and Carotid Dissections: Case Report

OBJECTIVES: Loeys-Dietz syndrome (LDS) is a rare genetic cause of stroke associated with connective tissue disorders but is not well known among stroke physicians.(1) The main objectives of this case report are to increase awareness of this condition and to improve stroke prevention at follow-up visits. METHODS: A patient with aortic and carotid artery dissection who had undergone 2 major aortic surgeries with mechanical composite graft and treated with full-dose anticoagulation was reevaluated by neurologists due to retinal hypoperfusion symptoms. After musculoskeletal examination, cervical ultrasonography, and computerized tomography angiography, he was referred for whole-genome sequencing. RESULTS: We found joint hypermobility, skin hyperelasticity, bifid uvula, and combined cervical artery dissections that caused intermittently decreased blood flow in the left ophthalmic artery and an acute asymptomatic embolic stroke. A novel pathogenic variant of LDS type 5 consisting of a heterogeneous nonsense variant c.1044C>A, p.(Cys384*) was found in the TGF-β 3 (TGFB3) gene. Consequently, anticoagulation was intensified, and at 1-year follow-up, the patient's symptoms improved. DISCUSSION: This novel genetic variant coupled to the patient's phenotype contributes to the knowledge of genetic causes of stroke. Patients with multiple arterial dissections and musculoskeletal features should be offered genetic testing and be carefully evaluated to avoid further cerebrovascular ischemic lesions.