Fatal ascending aortic dissection in a 12-year-old boy with previously undiagnosed Loeys-Dietz syndrome: A molecular...

Loeys-Dietz syndrome (LDS) is a heritable connective tissue disorder caused by pathogenic variants in genes involved in transforming growth factor-β signaling. It can present in childhood with fatal aortic dissection or rupture. We describe a medicolegal autopsy case of a 12-year-old boy who collapsed shortly after complaining of jaw pain and died despite resuscitation. Non-contrast postmortem computed tomography showed high-attenuation pericardial fluid, consistent with hemopericardium. At autopsy, 621 g of dark-red blood clot was present in the pericardial cavity, and the ascending aorta showed a longitudinal rupture with distal subadventitial hematoma. Pectus excavatum, bifid uvula, and tortuosity of the basilar and vertebral arteries were identified. Histological examination of the ascending aorta showed medial disruption, decreased smooth muscle cell nuclear density, focal mucoid extracellular matrix accumulation, and fragmentation, loss, and disorganization of elastic fibers. These findings prompted postmortem genetic testing. Whole-exome sequencing of blood-derived DNA identified a heterozygous pathogenic TGFBR1 variant, NM_004612.4:c.1460G>A (p.Arg487Gln), which was confirmed by Sanger sequencing. Targeted analysis of both parents did not detect the variant, supporting an apparently de novo event. Death was attributed to acute cardiac tamponade from ruptured ascending aortic dissection associated with TGFBR1-related LDS. The case emphasizes the practical value of correlating autopsy morphology with postmortem genetic testing in young sudden deaths due to aortic catastrophe.