Long QT interval in Turner syndrome--a high prevalence of LQTS gene mutations

Christian Trolle, Kristian H Mortensen, Lisbeth N Pedersen, Agnethe Berglund, Henrik K Jensen, Niels H Andersen, Claus H Gravholt, Christian Trolle, Kristian H Mortensen, Lisbeth N Pedersen, Agnethe Berglund, Henrik K Jensen, Niels H Andersen, Claus H Gravholt

Abstract

Objectives: QT-interval prolongation of unknown aetiology is common in Turner syndrome. This study set out to explore the presence of known long QT mutations in Turner syndrome and to examine the corrected QT-interval (QTc) over time and relate the findings to the Turner syndrome phenotype.

Methods: Adult women with Turner syndrome (n = 88) were examined thrice and 68 age-matched healthy controls were examined once. QTc was measured by one blinded reader (intra-reader variability: 0.7%), and adjusted for influence of heart rate by Bazett's (bQTc) and Hodges's formula (hQTc). The prevalence of mutations in genes related to Long QT syndrome was determined in women with Turner syndrome and a QTc >432.0 milliseconds (ms). Echocardiographic assessment of aortic valve morphology, 24-hour blood pressures and blood samples were done.

Results: The mean hQTc in women with Turner syndrome (414.0 ± 25.5 ms) compared to controls (390.4 ± 17.8 ms) was prolonged (p<0.001) and did not change over time (416.9 ± 22.6 vs. 415.6 ± 25.5 ms; p =0.4). 45,X karyotype was associated with increased hQTc prolongation compared to other Turner syndrome karyotypes (418.2 ± 24.8 vs. 407.6 ± 25.5 ms; p = 0.055). In women with Turner syndrome and a bQTc >432 ms, 7 had mutations in major Long QT syndrome genes (SCN5A and KCNH2) and one in a minor Long QT syndrome gene (KCNE2).

Conclusion: There is a high prevalence of mutations in the major LQTS genes in women with TS and prolonged QTc. It remains to be settled, whether these findings are related to the unexplained excess mortality in Turner women.

Clinical trial registration: NCT00624949. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol/sid/S0001FLI/selectaction/View/ts/3/uid/U000099E.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Heart rate plotted against QTc…
Figure 1. Heart rate plotted against QTc length.
a. Heart rate plotted against QTc length in women with TS. Hodges’s formula (open circles, dashed regression line, r2 = 0.012; p = 0.3) effectively omitted the dependence of QTc on heart rate when compared to Bazett’s formula (filled circles, solid regression line, r2 = 0.200; p<0.001). b. Heart rate plotted against QTc length in controls. Hodges’s formula (open circles, dashed regression line, r2 = 0.003; p = 0.7) effectively omitted the dependence of QTc on heart rate when compared to Bazett’s formula (filled circles, solid regression line, r2 = 0.161; p = 0.001). ms = milliseconds, bpm = beats per minute.

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