Cargando…

Clinical Implications and Gender Differences of KCNQ1 p.Gly168Arg Pathogenic Variant in Long QT Syndrome

Background: Long QT syndrome (LQTS) is an inheritable arrhythmogenic disorder associated with life-threatening arrhythmic events (LAEs). In general, patients with LQTS2 (KCNH2) and LQTS3 (SCN5A) are considered to be a greater risk of LAEs than LQTS1 (KCNQ1) patients. Gender differences are also impo...

Descripción completa

Detalles Bibliográficos
Autores principales: Lorca, Rebeca, Junco-Vicente, Alejandro, Martin-Fernandez, Maria, Pascual, Isaac, Aparicio, Andrea, Barja, Noemi, Cuesta-LLavona, Elias, Roces, Luis, Avanzas, Pablo, Moris, Cesar, Coto, Eliecer, Rodríguez Reguero, José Julían, Gómez, Juan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760054/
https://www.ncbi.nlm.nih.gov/pubmed/33256261
http://dx.doi.org/10.3390/jcm9123846
_version_ 1783627241703342080
author Lorca, Rebeca
Junco-Vicente, Alejandro
Martin-Fernandez, Maria
Pascual, Isaac
Aparicio, Andrea
Barja, Noemi
Cuesta-LLavona, Elias
Roces, Luis
Avanzas, Pablo
Moris, Cesar
Coto, Eliecer
Rodríguez Reguero, José Julían
Gómez, Juan
author_facet Lorca, Rebeca
Junco-Vicente, Alejandro
Martin-Fernandez, Maria
Pascual, Isaac
Aparicio, Andrea
Barja, Noemi
Cuesta-LLavona, Elias
Roces, Luis
Avanzas, Pablo
Moris, Cesar
Coto, Eliecer
Rodríguez Reguero, José Julían
Gómez, Juan
author_sort Lorca, Rebeca
collection PubMed
description Background: Long QT syndrome (LQTS) is an inheritable arrhythmogenic disorder associated with life-threatening arrhythmic events (LAEs). In general, patients with LQTS2 (KCNH2) and LQTS3 (SCN5A) are considered to be a greater risk of LAEs than LQTS1 (KCNQ1) patients. Gender differences are also important. Series analyzing families with the same pathogenic variants may help in the progress of elaborating strong specific genotype-phenotype management strategies. In this manuscript, we describe the phenotype of seven unrelated families, carriers of the KCNQ1 G168R pathogenic variant. Methods: we identified all consecutive index cases referred for genetic testing with LQTS diagnosis carriers of KCNQ1 G168R variant. Genetic and clinical screening for all available relatives was performed. Results: we evaluated seven unrelated families, with a total 34 KCNQ1 G168R carriers (two obligated carriers died without available EKGs to evaluate the phenotype). All index cases but one were women and three of them presented with aborted sudden cardiac death (SCD) or syncope. The presence of sudden death in these families is notable, with a total of nine unexplained sudden deaths and four aborted SCD. Phenotype penetrance was 100% in women and 37.5% in men. Conclusions: KCNQ1 G168R is a pathogenic variant, with a high penetrance among women and mild penetrance among men. Risk for LAEs in this variant seems not negligible, especially among woman, and risk stratification should always be carefully evaluated.
format Online
Article
Text
id pubmed-7760054
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-77600542020-12-26 Clinical Implications and Gender Differences of KCNQ1 p.Gly168Arg Pathogenic Variant in Long QT Syndrome Lorca, Rebeca Junco-Vicente, Alejandro Martin-Fernandez, Maria Pascual, Isaac Aparicio, Andrea Barja, Noemi Cuesta-LLavona, Elias Roces, Luis Avanzas, Pablo Moris, Cesar Coto, Eliecer Rodríguez Reguero, José Julían Gómez, Juan J Clin Med Article Background: Long QT syndrome (LQTS) is an inheritable arrhythmogenic disorder associated with life-threatening arrhythmic events (LAEs). In general, patients with LQTS2 (KCNH2) and LQTS3 (SCN5A) are considered to be a greater risk of LAEs than LQTS1 (KCNQ1) patients. Gender differences are also important. Series analyzing families with the same pathogenic variants may help in the progress of elaborating strong specific genotype-phenotype management strategies. In this manuscript, we describe the phenotype of seven unrelated families, carriers of the KCNQ1 G168R pathogenic variant. Methods: we identified all consecutive index cases referred for genetic testing with LQTS diagnosis carriers of KCNQ1 G168R variant. Genetic and clinical screening for all available relatives was performed. Results: we evaluated seven unrelated families, with a total 34 KCNQ1 G168R carriers (two obligated carriers died without available EKGs to evaluate the phenotype). All index cases but one were women and three of them presented with aborted sudden cardiac death (SCD) or syncope. The presence of sudden death in these families is notable, with a total of nine unexplained sudden deaths and four aborted SCD. Phenotype penetrance was 100% in women and 37.5% in men. Conclusions: KCNQ1 G168R is a pathogenic variant, with a high penetrance among women and mild penetrance among men. Risk for LAEs in this variant seems not negligible, especially among woman, and risk stratification should always be carefully evaluated. MDPI 2020-11-26 /pmc/articles/PMC7760054/ /pubmed/33256261 http://dx.doi.org/10.3390/jcm9123846 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lorca, Rebeca
Junco-Vicente, Alejandro
Martin-Fernandez, Maria
Pascual, Isaac
Aparicio, Andrea
Barja, Noemi
Cuesta-LLavona, Elias
Roces, Luis
Avanzas, Pablo
Moris, Cesar
Coto, Eliecer
Rodríguez Reguero, José Julían
Gómez, Juan
Clinical Implications and Gender Differences of KCNQ1 p.Gly168Arg Pathogenic Variant in Long QT Syndrome
title Clinical Implications and Gender Differences of KCNQ1 p.Gly168Arg Pathogenic Variant in Long QT Syndrome
title_full Clinical Implications and Gender Differences of KCNQ1 p.Gly168Arg Pathogenic Variant in Long QT Syndrome
title_fullStr Clinical Implications and Gender Differences of KCNQ1 p.Gly168Arg Pathogenic Variant in Long QT Syndrome
title_full_unstemmed Clinical Implications and Gender Differences of KCNQ1 p.Gly168Arg Pathogenic Variant in Long QT Syndrome
title_short Clinical Implications and Gender Differences of KCNQ1 p.Gly168Arg Pathogenic Variant in Long QT Syndrome
title_sort clinical implications and gender differences of kcnq1 p.gly168arg pathogenic variant in long qt syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760054/
https://www.ncbi.nlm.nih.gov/pubmed/33256261
http://dx.doi.org/10.3390/jcm9123846
work_keys_str_mv AT lorcarebeca clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome
AT juncovicentealejandro clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome
AT martinfernandezmaria clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome
AT pascualisaac clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome
AT aparicioandrea clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome
AT barjanoemi clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome
AT cuestallavonaelias clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome
AT rocesluis clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome
AT avanzaspablo clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome
AT moriscesar clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome
AT cotoeliecer clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome
AT rodriguezreguerojosejulian clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome
AT gomezjuan clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome