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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2018

Open Access 01-12-2018 | Research article

Clinical and molecular genetic risk determinants in adult long QT syndrome type 1 and 2 patients

Koponen et al. Follow-up of adult LQTS patients

Authors: Mikael Koponen, Aki S. Havulinna, Annukka Marjamaa, Annukka M. Tuiskula, Veikko Salomaa, Päivi J. Laitinen-Forsblom, Kirsi Piippo, Lauri Toivonen, Kimmo Kontula, Matti Viitasalo, Heikki Swan

Published in: BMC Medical Genetics | Issue 1/2018

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Abstract

Background

Long QT syndrome (LQTS) is an inherited cardiac disorder predisposing to sudden cardiac death (SCD). We studied factors affecting the clinical course of genetically confirmed patients, in particular those not receiving β-blocker treatment. In addition, an attempt was made to associate risk of events to specific types of KCNQ1 and KCNH2 mutations.

Methods

A follow-up study covering a mean of 18.6 ± 6.1 years was conducted in 867 genetically confirmed LQT1 and LQT2 patients and 654 non-carrier relatives aged 18–40 years. Cox regression models were used to evaluate the contribution of clinical and genetic risk factors to cardiac events.

Results

In mutation carriers, risk factors for cardiac events before initiation of β-blocker included LQT2 genotype (hazard ratio [HR] = 2.1, p = 0.002), female gender (HR = 3.2, p < 0.001), a cardiac event before the age of 18 years (HR = 5.9, p < 0.001), and QTc ≥500 ms (vs < 470 ms, HR = 2.7, p = 0.001). LQT1 patients carrying the KCNQ1 D317N mutation were at higher risk (HR = 3.0–3.9, p < 0.001–0.03) compared to G589D, c.1129-2A > G and other KCNQ1 mutation carriers after adjusting for gender, QTc duration, and cardiac events before age 18. KCNH2 c.453delC, L552S and R176W mutations associated with lower risk (HR = 0.11–0.23, p < 0.001) than other KCNH2 mutations.

Conclusions

LQT2 (compared to LQT1), female gender, a cardiac event before age 18, and long QT interval increased the risk of cardiac events in LQTS patients aged 18 to 40 years. The nature of the underlying mutation may be associated with risk variation in both LQT1 and LQT2. The identification of high-risk and low-risk mutations may enhance risk stratification.
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Metadata
Title
Clinical and molecular genetic risk determinants in adult long QT syndrome type 1 and 2 patients
Koponen et al. Follow-up of adult LQTS patients
Authors
Mikael Koponen
Aki S. Havulinna
Annukka Marjamaa
Annukka M. Tuiskula
Veikko Salomaa
Päivi J. Laitinen-Forsblom
Kirsi Piippo
Lauri Toivonen
Kimmo Kontula
Matti Viitasalo
Heikki Swan
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2018
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-018-0574-0

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