We report the first case of a patient with neurofibromatosis type 1 (NF1) concurrently presenting with severe aortic regurgitation with valvular vegetations, left ventricular hypertrophy/enlargement, left atrial dilation, mitral regurgitation, and a PAI-1 4G/5G heterozygous genotype, ultimately leading to cerebral and splenic infarction. The gene discussed is SERPINE1; the disease is mitral valve insufficiency.