Abstract 18972: A 36-Year-Old Man with Stroke and Severe Hyperlipidemia: From Phenotype to Genotype

Abstract

A 36-year-old man with a history of hypertension and hyperlipidemia was admitted to the hospital with headaches, a left visual field deficit and a right occipital lobe infarct. Family history is notable for multiple maternal relatives with premature coronary artery disease and severe hyperlipidemia. Laboratory testing revealed an LDL level of 325 mg/dl. Echocardiography demonstrated a bicuspid aortic valve and two highly mobile thrombi at the sinotubular junction. Because there was no aortic false lumen and the clinical picture was most suspicious for a ruptured aortic root atheroma, we administered intravenous heparin with plans for aortic thrombectomy pending his hemodynamics, neurological status and changes in the echocardiographic apperance of the presumed thrombi. On day three, the patient experienced acute chest pain and ST elevation concerning for abrupt occlusion of the right coronary artery. He was taken emergently to the operating room where two thrombi_one of which was lodged in the right coronary ostium_were removed and aortic endarterectomy was performed. Histology of the aortic specimen showed atherosclerosis and inflammation but no evidence of medial degeneration. The histologic evidence of atherosclerosis focused attention on the patient’s personal and family history of severe hypercholesterolemia. To assess for a genetic defect in cholesterol metabolism, we directly sequenced the LDL receptor gene and identified a heterozygous missense mutation associated with familial hypercholesterolemia (FH). Aortic root disease is common in FH homozygotes, but its presence in a heterozygote suggests an additional inherited or acquired risk factor and prompts further investigation. The bicuspid valve raises the possibility of a subclinical aortic condition that may have contributed to this unusual syndrome. This case directly illustrates the consequences of aortic plaque rupture and emphasizes the multidisciplinary clinical approaches that are central to understanding the complex links between genotype and phenotype even in a well-characterized "simple" monogenic disorder.