Abstract
Long QT syndrome (LQTS) is one the best characterized disorders among all inherited arrhythmogenic syndromes. A multi-parametric risk stratification scheme, which includes clinical variables (QTc, gender) and the main LQTS genotypes, was defined in the early 2000s and is currently used in clinical practice. However, the evidence of a marked phenotypic variability, even in the presence of the same genetic mutation has puzzled many investigators since the discovery of LQTS genes. Practically, variable expression in LQTS often limits the predictive accuracy of risk stratification markers. Therefore, in a subset of cases, the identification of subjects at a high risk of life-threatening arrhythmias and sudden death is difficult. The discovery of common genetic variants that explain the heritable components of the human electrocardiogram, including QT interval, generated the hypothesis that genetic modifiers may account for phenotypical variability in LQTS. Despite the fact that multiple SNPs have been linked to QT interval duration, clinical applications of any findings are limited by the small effect sizes conferred by single SNPs and incomplete knowledge on their functional consequences. Nevertheless, the possibility of introducing SNP genotyping in risk stratification schemes to improve patient-specificity is an attractive goal. Here we review the currently available evidence and future perspectives for the inclusion of genetic modifiers in the clinical management of LQTS.
| Original language | English |
|---|---|
| Pages (from-to) | 17-24 |
| Number of pages | 8 |
| Journal | Current Opinion in Genetics and Development |
| Volume | 33 |
| DOIs | |
| Publication status | Published - Aug 1 2015 |
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ASJC Scopus subject areas
- Genetics
- Developmental Biology
Cite this
Genetic modulators of the phenotype in the long QT syndrome : state of the art and clinical impact. / Napolitano, Carlo; Novelli, Valeria; Francis, Matthew D.; Priori, Silvia G.
In: Current Opinion in Genetics and Development, Vol. 33, 01.08.2015, p. 17-24.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genetic modulators of the phenotype in the long QT syndrome
T2 - state of the art and clinical impact
AU - Napolitano, Carlo
AU - Novelli, Valeria
AU - Francis, Matthew D.
AU - Priori, Silvia G.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - Long QT syndrome (LQTS) is one the best characterized disorders among all inherited arrhythmogenic syndromes. A multi-parametric risk stratification scheme, which includes clinical variables (QTc, gender) and the main LQTS genotypes, was defined in the early 2000s and is currently used in clinical practice. However, the evidence of a marked phenotypic variability, even in the presence of the same genetic mutation has puzzled many investigators since the discovery of LQTS genes. Practically, variable expression in LQTS often limits the predictive accuracy of risk stratification markers. Therefore, in a subset of cases, the identification of subjects at a high risk of life-threatening arrhythmias and sudden death is difficult. The discovery of common genetic variants that explain the heritable components of the human electrocardiogram, including QT interval, generated the hypothesis that genetic modifiers may account for phenotypical variability in LQTS. Despite the fact that multiple SNPs have been linked to QT interval duration, clinical applications of any findings are limited by the small effect sizes conferred by single SNPs and incomplete knowledge on their functional consequences. Nevertheless, the possibility of introducing SNP genotyping in risk stratification schemes to improve patient-specificity is an attractive goal. Here we review the currently available evidence and future perspectives for the inclusion of genetic modifiers in the clinical management of LQTS.
AB - Long QT syndrome (LQTS) is one the best characterized disorders among all inherited arrhythmogenic syndromes. A multi-parametric risk stratification scheme, which includes clinical variables (QTc, gender) and the main LQTS genotypes, was defined in the early 2000s and is currently used in clinical practice. However, the evidence of a marked phenotypic variability, even in the presence of the same genetic mutation has puzzled many investigators since the discovery of LQTS genes. Practically, variable expression in LQTS often limits the predictive accuracy of risk stratification markers. Therefore, in a subset of cases, the identification of subjects at a high risk of life-threatening arrhythmias and sudden death is difficult. The discovery of common genetic variants that explain the heritable components of the human electrocardiogram, including QT interval, generated the hypothesis that genetic modifiers may account for phenotypical variability in LQTS. Despite the fact that multiple SNPs have been linked to QT interval duration, clinical applications of any findings are limited by the small effect sizes conferred by single SNPs and incomplete knowledge on their functional consequences. Nevertheless, the possibility of introducing SNP genotyping in risk stratification schemes to improve patient-specificity is an attractive goal. Here we review the currently available evidence and future perspectives for the inclusion of genetic modifiers in the clinical management of LQTS.
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U2 - 10.1016/j.gde.2015.06.009
DO - 10.1016/j.gde.2015.06.009
M3 - Article
C2 - 26241467
AN - SCOPUS:84939235248
VL - 33
SP - 17
EP - 24
JO - Current Opinion in Genetics and Development
JF - Current Opinion in Genetics and Development
SN - 0959-437X
ER -