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Inferolateral T wave inversion in athletes: phenotype-genotype correlation

Abstract

Aims

Significant T wave inversion in young asymptomatic athletes is rare but poses a significant clinical challenge. Pre-participation sports screening programs identify such subjects. Clinical concern that such ECG changes represent an occult cardiomyopathy or forme fruste hypertrophic cardiomyopathy leads to diagnostic and therapeutic dilemma. We sought to genotype a cohort of such subjects with a normal cardiac phenotype identified in our unit over a 3-year period.

Methods

Ten athletes were referred from external screening. All exhibited deep T wave inversion inferolaterally. All had negative family history for sudden death and had a normal phenotype. A panel of 133 cardiac genes were screened.

Results

Ten male subjects with mean age of 39 years were screened. Seven had no evidence of mutations. Three subjects demonstrated variants of uncertain significance in 5 different genes: alpha-2-actinin (ACTN2), myopalladin (MYPN), the calcium channel genes CACNA1C and TRPM4 and potassium channel gene KCNQ1. The variants found have not been described in cardiomyopathies or channelopathies. At 3-year follow-up, one patient had undergone detraining, and his ECG showed complete resolution of all T wave changes. He did not have any demonstrated variants.

Conclusions

The absence of mutations in target genes and heterogeneous sequence variations identified in this study suggest that inferolateral T wave inversion in athletes without a phenotype may potentially represent a benign repolarization syndrome related to athletic adaptation. This was the first study to assess a phenotype-genotype correlation in this population. Further genetic studies need to be undertaken in this area.

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Acknowledgements

The authors wish to acknowledge Ed Donovan and the team at Advance Medical Services, Cork, for their contribution of participants. We also wish to acknowledge Blueprint Genetics for their genotyping.

Availability of data and material

All data is available on request.

Funding

Funding for the genotyping was provided by the Mercy Hospital Foundation.

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed to the study conception and design. All authors contributed to and reviewed the final manuscript.

Corresponding author

Correspondence to Heather Cronin.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethics approval

Ethical approval was granted by the Clinical Research and Ethics Committee of the Cork teaching hospitals.

Consent to participate

Informed written consent was obtained from all participants prior to enrolment.

Consent for publication

All participants consented to the data being published in an anonymised manner.

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Appendix

Appendix

Blueprint Genetics Heart panel (version 1.1, updated May 6, 2014) consists of genes associated with hereditary cardiomyopathies and channelopathies:

ABCC9, ACADVL, ACTC1, ACTN2, AGL, AKAP9, ANK2, ANKRD1, ATP5E, BAG3, BRAF, CACNA1C, CACNA2D1, CACNB2, CALM1

CALM2, CALR3, CASQ2, CAV3, CBL, COA5, CRYAB, CSRP3, CTF1, CTNNA3, DES, DMD, DMPK, DNAJC19, DNM1L, DOLK, DPP6, DSC2, DSG2, DSP, DTNA

EMD, EYA4, FHL1, FHL2, FKTN, FOXRED1, FXN, GAA, GATAD1, GLA, GLB1, GPD1L, GUSB, HCN4, HFE, HRAS, ILK, JPH2, JUP, KCND3, KCNE1, KCNE1L

KCNE2, KCNE3, KCNH2, KCNJ2, KCNJ5, KCNJ8, KCNQ1, KRAS, LAMA4, LAMP2, LDB3, LMNA, MAP2K1, MAP2K2, MRPL3, MIB1, MYBPC3, MYH6, MYH7

MYL2, MYL3, MYLK2, MYOM1, MYOZ2, MYPN, NEBL, NEXN, NOS1AP, NRAS, PDLIM3, PKP2, PLN, PRKAG2, PSEN1, PSEN2, PTPN11, RAF1, RANGRF

RBM20, RYR2, SCN1B, SCN2B, SCN3B, SCN4B, SCN5A, SCO2, SDHA, SGCD, SHOC2, SLC25A3, SLMAP, SNTA1, SOS1, SPRED1, SYNE1, SYNE2, TAZ

TCAP, TGFB3, TMEM43, TMEM70, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TRDN, TRIM63, TRPM4, TSFM, TTN, TTR, TXNRD2, VCL, XK

The panel is targeting all protein coding exons and exon-intron boundaries of all target genes. It also covers a number of mutations located outside these coding regions.

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Cronin, H., Crinion, D., Kerins, D. et al. Inferolateral T wave inversion in athletes: phenotype-genotype correlation. Ir J Med Sci 189, 1283–1287 (2020). https://doi.org/10.1007/s11845-020-02239-x

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Keywords

  • Athletic adaptation
  • Cardiomyopathy
  • Genetics
  • Repolarization abnormalities
  • Sports screening
  • T wave inversion