The Importance of Genetic Testing in a Case of Sudden Death in Hypertrophic Cardiomyopathy due to Troponin I Mutation

Abstract

Sudden death due to hypertrophic cardiomyopathy (HCM) is uncommon. Most cases of HCM are due to mutations in sarcomeric proteins. Mutations of the cardiac troponin I gene TNNI3 are rare. Over 15 mutations of the TNNI3 gene have been identified; the clinical, imaging and pathologic findings within the small subcategory are very diverse. While asymptomatic patients do not generally receive therapy, the entire group may be at risk of sudden death. Thus, affected individuals and their family members may require heightened surveillance. As such, accurate diagnosis at postmortem examination is important as it may have a direct impact on the health and well-being of surviving family members. We present the case of a 36-year-old man who collapsed and died while jogging. His sister had been recently diagnosed with hypertrophic cardiomyopathy. Consequently, the decedent had undergone transthoracic echocardiography that demonstrated only mild features suggestive of hypertrophic cardiomyopathy including non-obstructive asymmetric septal wall thickening of less than 30 mm in the absence of systolic anterior motion of the mitral valve or cardiomegaly. The autopsy confirmed the presence of mild septal hypertrophy (maximum 23 mm thickness) in the absence of cardiomegaly. Histologic features were typical of hypertrophic cardiomyopathy including septal myofiber disarray and nuclear enlargement. Mutational analysis of frozen myocardium demonstrated an Arg162Gln substitution in the cardiac troponin I gene (TNNI3) involving exon 7. This case highlights the importance of molecular/genetic analysis in the setting of sudden natural death, from both diagnostic and public health perspectives.