TNNT2 Mutation Affects the Progression of Dilated Cardiomyopathy in Children

Genetic mutations play an important role in pediatric cardiomyopathy. However, whether different genetic factors contribute to the rate of disease progression remains unclear.

To explore the role of genetic mutations in disease progression in pediatric cardiomyopathy.

We collected basic clinical data on 67 children and 166 adults who underwent heart transplantation for cardiomyopathy, and conducted whole-exome sequencing and standard pathology examinations on these patients. We then compared the prevalence of pathogenic genes and their occurring in the same type of myocardium between children and adult heart transplantation recipients, with a focus on the age of onset and duration of disease.

Of 67 children, 33 (49.3%; 95% CI: 32.2%-55.3%) carried mutation genes. The proportion of mutations varied significantly among different types of cardiomyopathies (P = 0.003). The median [IQR] time from diagnosis to transplant was significantly shorter in children compared to adults in cases of dilated cardiomyopathy (DCM) (12 [1-23] vs 103 [5-201] months, P < 0.001), hypertrophic cardiomyopathy (32 [14.5-46.5] vs 234 [183-285] months, P = 0.002) and arrhythmogenic cardiomyopathy (28 [14.5-41.5] vs 127 [86-168] months, P < 0.001). Children with DCM were more likely to carry the TNNT2 mutation compared to adults with DCM (P = 0.001), and heart failure progressed more rapidly in children with this mutation versus adults (19 vs 128 months, P = 0.002). The most common mutation site in these children was p.K220del.

TNNT2 mutations were associated with shorter time from diagnosis to transplantation in children with DCM. These findings suggest that early genetic evaluation may aid in risk stratification and inform clinical management in pediatric cardiomyopathy.