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


CONCLUSIONS
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.


BACKGROUND
NCT00624949. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol/sid/S0001FLI/selectaction/View/ts/3/uid/U000099E.
Department of Endocrinology and Internal Medicine and Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark.
Christian
C
Trolle
Kristian H
KH
Mortensen
Lisbeth N
LN
Pedersen
Agnethe
A
Berglund
Henrik K
HK
Jensen
Niels H
NH
Andersen
Claus H
CH
Gravholt
D000368:Aged; D001021:Aortic Valve / Q000000981:diagnostic imaging / Q000473:pathology; D016022:Case-Control Studies; D016757:Death, Sudden, Cardiac / Q000209:etiology; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D005260:Female; D005838:Genotype; D006339:Heart Rate; D006801:Humans; D007621:Karyotyping; D008133:Long QT Syndrome / Q000150:complications / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D008875:Middle Aged; D059645:Mutation Rate; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D016019:Survival Analysis; D014424:Turner Syndrome / Q000150:complications / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D014463:Ultrasonography
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C489619:KCNE2 protein, human; C000606913:KCNH2 protein, human; D062554:NAV1.5 Voltage-Gated Sodium Channel; D024642:Potassium Channels, Voltage-Gated; C568320:SCN5A protein, human