Key result
Genetic screening of 10 male athletes with inferolateral T-wave inversion and normal cardiac phenotype revealed variants of uncertain significance in 30% of subjects.
Why the study?
Does genetic testing identify pathogenic mutations in asymptomatic athletes with inferolateral T-wave inversion and normal cardiac imaging?
Cohort (n=10)
Does genetic testing identify pathogenic mutations in asymptomatic athletes with inferolateral T-wave inversion and normal cardiac imaging?
Genetic screening of athletes with isolated inferolateral T-wave inversion and normal imaging yielded only variants of uncertain significance in a minority of subjects.
Caution against routine genetic screening in athletes with this ECG pattern; leaves open the clinical relevance of VUS.
Introduction: Significant T-wave inversion in young asymptomatic athletes is rare, but poses a significant clinical challenge. Pre-participation sports screening programs can identify such subjects. The clinical suspicion is that such ECG changes represent an occult cardiomyopathy. It has been suggested that such ECG changes may be due to mutations in genes encoding myofilament proteins and forme fruste hypertrophic cardiomyopathy. We sought to genotype a prospective cohort of such subjects with no discernible phenotype identified in our unit over a 3 year period. Methods: Ten athletes were referred from external pre-participation screening. All exhibited prominent deep symmetrical T wave inversion in the inferolateral leads. All had negative family history and a normal phenotype based on 2D echocardiography, Holter monitoring, stress testing and cardiac MRI. Next generation DNA sequencing was used to screen a panel of 133 cardiac-specific genes associated with cardiomyopathy and/or channelopathy, confirmed by Sanger sequencing. Results: All subjects were male with a mean age of 39 years. 7 had no evidence of sequence variation in the genetic panel. 3 patients demonstrated variants of uncertain significance in 5 different cardiac genes: alpha-2-actinin (ACTN2), myopalladin (MYPN), the calcium channel genes CACNA1C and TRPM4 and potassium channel gene KCNQ1. Both ACTN2 and MYPN genes code for structural proteins in the sarcomere and other variants in these proteins have been described in hypertrophic and dilated cardiomyopathy cases. At 3 year follow up, one patient had undergone detraining and his ECG interestingly showed complete resolution of all T wave changes. He did not have any demonstrated variants.
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Cronin et al. (2018) conducted a cohort in Inferolateral T-wave inversion in athletes (n=10). Next generation DNA sequencing was evaluated on Presence of sequence variation in a panel of 133 cardiac-specific genes. Genetic screening of 10 male athletes with inferolateral T-wave inversion and normal cardiac phenotype revealed variants of uncertain significance in 30% of subjects.
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