Tale of two hearts: a TNNT2 hypertrophic cardiomyopathy case report

Hypertrophic cardiomyopathy (HCM) is a heritable cardiomyopathy that is predominantly caused by pathogenic mutations in sarcomeric proteins. Here we report two individuals, a mother and her daughter, both heterozygous carriers of the same HCM-causing mutation in cardiac Troponin T (TNNT2). Despite sharing an identical pathogenic variant, the two individuals had very different manifestations of the disease. While one patient presented with sudden cardiac death, recurrent tachyarrhythmia, and findings of massive left ventricular hypertrophy, the other patient manifested with extensive abnormal myocardial delayed enhancement despite normal ventricular wall thickness and has remained relatively asymptomatic. Recognition of the marked incomplete penetrance and variable expressivity possible in a single TNNT2-positive family has potential to guide HCM patient care.

Automated summary

In this study, we report on a mother and her daughter who are both heterozygous carriers of the same pathogenic mutation in TNNT2, leading to hypertrophic cardiomyopathy. Despite sharing the same mutation, they exhibited very different phenotypes. One patient presented with severe symptoms including sudden cardiac death, while the other patient showed abnormal myocardial delayed enhancement but remained relatively asymptomatic. Recognizing the incomplete penetrance and variable expressivity of TNNT2 mutations within a single family has the potential to guide patient care for hypertrophic cardiomyopathy.