Abstract
ObjectivesQT-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.MethodsAdult 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.ResultsThe 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).ConclusionThere 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 RegistrationNCT00624949. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol/sid/S0001FLI/selectaction/View/ts/3/uid/U000099E.
Highlights
The corrected QT interval (QTc-interval) is prolonged in 33% of children and 20% of adults with Turner syndrome (TS) [1,2,3]
Heart rate was plotted against QTc to clarify the contribution of heart rate to differences in the QTc-interval (Figure 1A and B)
There was a positive correlation between heart rate and bQTc among women with TS (R = 0.448; p,0.001) and controls (R = 0.401; p,0.001), which was not present using hQTc (Figure 1A and B)
Summary
The corrected QT interval (QTc-interval) is prolonged in 33% of children and 20% of adults with Turner syndrome (TS) [1,2,3]. A prolonged QTc-interval is associated with increased risk of sudden death in the general population [4]. Long QT syndrome (LQTS) in general is characterized by prolongation of the QT-interval in association with the risk of Torsade de Point. In TS the mechanism behind the QTc prolongation is unknown. Increased morbidity and mortality are present due to congenital heart disease, ischemic heart disease, hypertension, and diabetes [8,9,10]. Whether a QTcinterval prolongation contributes to the increased excess mortality in women with TS remains to be solved [9]
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