Marked, transient, emotion-triggered QT accentuation in an adolescent female with type 1 long QT syndrome

2014 ◽  
Vol 25 (2) ◽  
pp. 376-379 ◽  
Author(s):  
Heather N. Anderson ◽  
Beth A. Medford ◽  
Michael J. Ackerman
Keyword(s):  
Emotional Distress ◽  
Long Qt Syndrome ◽  
Frameshift Mutation ◽  
Qtc Interval ◽  
Cardiac Events ◽  
Long Qt ◽  
Cardiac Repolarisation ◽  
Genetic Subtype ◽  
Qt Syndrome

AbstractType 1 long QT syndrome is the most common long QT syndrome genetic subtype. Exercise and emotional stress can precipitate sudden cardiac events in patients with type 1 long QT syndrome; however, the precise mechanism remains elusive. We report the case of a teenage girl with type 1 long QT syndrome secondary to a rare frameshift mutation (p. L191fs+90X) in the KCNQ1-encoded Kv7.1 potassium channel. During emotional distress, her continuous QTc recordings precipitously increased, peaking within minutes to 669 ms and then returning to baseline (520 ms) as she calmed without concomitant increase in heart rate. This is the first described case documenting transient, marked accentuation of the QTc interval in a long QT syndrome patient during emotional distress. Such events may be triggered by transient accentuation of the intrinsic perturbation in cardiac repolarisation and increase the risk of degeneration to a ventricular arrhythmia. This case illustrates the need improved understanding of the complex interaction between emotion and cardiac stability in patients with long QT syndrome.

scholarly journals Effect of Age and Sex on the QTc Interval in Children and Adolescents With Type 1 and 2 Long-QT Syndrome

2017 ◽  
Vol 10 (4) ◽  
Author(s):  
Arja S. Vink ◽  
Sally-Ann B. Clur ◽  
Ronald B. Geskus ◽  
Andreas C. Blank ◽  
Charlotte C.A. De Kezel ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Long Qt Syndrome ◽  
Qtc Interval ◽  
Long Qt ◽  
Qt Syndrome ◽  
Effect Of Age ◽  
Age And Sex

scholarly journals Stop-codon and C-terminal nonsense mutations are associated with a lower risk of cardiac events in patients with long QT syndrome type 1

Heart Rhythm ◽  
2016 ◽  
Vol 13 (1) ◽  
pp. 122-131 ◽  
Author(s):  
Martin H. Ruwald ◽  
Xiaorong Xu Parks ◽  
Arthur J. Moss ◽  
Wojciech Zareba ◽  
Jayson Baman ◽  
...  
Keyword(s):  
Long Qt Syndrome ◽  
Lower Risk ◽  
Stop Codon ◽  
Syndrome Type ◽  
Cardiac Events ◽  
Long Qt ◽  
Nonsense Mutations ◽  
Qt Syndrome

Systematic Evaluation of KCNQ1 variant using ACMG/AMP Guidelines and Risk Stratification in Long QT Syndrome Type 1

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Kashiwa ◽  
T Aiba ◽  
H Makimoto ◽  
N Yagihara ◽  
S Ohno ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Long Qt Syndrome ◽  
Family Members ◽  
Qtc Interval ◽  
Syndrome Type ◽  
Long Qt ◽  
C Terminus ◽  
Qt Syndrome ◽  
Research Grant

Abstract Background Mutation/variant-site specific risk stratification in long-QT syndrome type 1 (LQT1) has been well investigated, but it is still challenging to adopt current enormous genomic information to clinical aspects caused by each mutation/variant. We assessed a novel variant-specific risk stratification in LQT1 patients. Methods We classified a pathogenicity of 142 KCNQ1 variants among 927 LQT1 patients (536 probands and 391 family members) based on the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) guidelines and evaluated whether the ACMG/AMP-based classification was associated with arrhythmic risk in LQT1 patients. Results Among 142 KCNQ1 variants, 60 (42.3%), 58 (40.8%), and 24 (16.9%) variants were classified into pathogenic (P), likely pathogenic (LP), and variant of unknown significance (VUS), respectively. The ACMG/AMP guideline-based classification was significantly associated with syncopal events (particularly those during exercise) and LQT risk score (Schwartz score) in overall population. On the other hand, arrhythmic risk was completely different between probands and families even in the same variants. The baseline QTc interval and variant location could stratify the risk in family members but not in probands, however, the ACMG/AMP-based KCNQ1 variant classification stratified the risk in LQT1 probands as well as family members. Multivariate analysis showed that proband (HR=2.52; 95% CI: 1.93–3.30; p<0.0001), longer QTc interval (≥500ms) (HR=1.41; 95% CI: 1.11–1.79; p<0.0001), variants at membrane spanning (MS) (vs. those at N/C terminus) (HR=1.40; 95% CI: 1.07–1.85; p=0.02), C-loop (vs. N/C terminus) (HR=1.58; 95% CI: 1.11–2.24; p=0.01), and P variants [(vs. LP) (HR=1.71; 95% CI: 1.33–2.23; p<0.0001), (vs. VUS) (HR=1.96; 95% CI: 1.19–3.46; p=0.007)] were significantly associated with syncopal events. A clinical score (0–4) based on the proband, QTc (≥500ms), variant location (MS or C-loop) and P variant by the ACMG/AMP guidelines allowed identification of patients more likely to have arrhythmic events (Figure A and B). Conclusion Comprehensive evaluation of clinical findings and pathogenicity of KCNQ1 variants based on the ACMG/AMP-based evaluation may stratify arrhythmic risk of congenital long-QT syndrome type 1. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Health Science Research Grant from the Ministry of Health,Labor and Welfare of Japan for Clinical Research on Measures for Intractable Diseases (H24-033, H26-040, H27-032) and a research grant from the Japan Agency for Medical Research and Development (AMED) (15km0305015h0101, 16ek0210073h0001)

β1-Adrenergic receptor polymorphisms, QTc interval and occurrence of symptoms in type 1 of long QT syndrome

2007 ◽  
Vol 118 (2) ◽  
pp. 197-202 ◽  
Author(s):  
Kristian J. Paavonen ◽  
Heikki Swan ◽  
Kirsi Piippo ◽  
Päivi Laitinen ◽  
Heidi Fodstad ◽  
...  
Keyword(s):  
Long Qt Syndrome ◽  
Adrenergic Receptor ◽  
Qtc Interval ◽  
Long Qt ◽  
Qt Syndrome

Abstract 12257: Calmodulin Interacting Genes as a Novel Candidate for Pathogenesis of Long-QT Syndrome

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Takeshi Aiba ◽  
Daichi Shigemizu ◽  
Hidewaki Nakagawa ◽  
Kouichi Ozaki ◽  
Fuyuki Miya ◽  
...  
Keyword(s):  
Long Qt Syndrome ◽  
De Novo ◽  
Association Studies ◽  
Polymorphic Ventricular Tachycardia ◽  
Compound Heterozygous ◽  
Qtc Interval ◽  
Cardiac Events ◽  
Long Qt ◽  
Network Analyses ◽  
Qt Syndrome

Background: Approximately 30% of long-QT syndrome (LQTS) cases remains genetically elusive. Here, we investigated usefulness of the whole exon sequencing (WES) by next-generation sequencing for identification of novel pathogenic candidates which directly or indirectly interact with proteins encoded by known LQTS genes. Methods: Of 1815 Japanese LQTS cohort patients, WES was performed in 59 LQTS patients and 61 unaffected individuals from 35 families and 138 unrelated LQTS cases, all were screened major LQTS genes such as KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2 and KCNJ2. After WES, the genes known as inherited arrhythmias were screened by the Human Gene Mutation Database, and the Sanger sequencing was also referred for validation of the mutations and common variants were excluded by the public (1000G, ESP6500 and dbSNP) and Riken database. Results: Total 92 candidate mutations including 11 de novo, 5 recessive (2 homozygous and 3 compound heterozygous) and 73 dominant mutations in 88 genes were identified in 23 of the 35 families. Protein-protein interaction network analyses revealed ten new pathogenic candidates (WDR26, RYR2, UBR5, UBR4, KIF21B, CIT, SIRT6, PIK3CG, PI4KA and RIMS1) that directly or indirectly interact with proteins encoded by known LQTS genes. Furthermore, gene based association studies identified an additional novel candidate; SLC2A5. Taken together, mutations in these new candidates or known LQTS genes were identified in 13 of the 35(37%) genotype-unknown LQTS families. Moreover, 5 of the 11 newly identified candidates directly interact with calmodulin (CaM). Subsequent variant analysis in the independent set of 138 cases identified 16 variants in the 11 genes, of which, 14 (87.5%) were in the CaM-interacting genes and 8 of them were in RYR2. Many of the patients with RyR2 mutation had similar exercise-induced cardiac events (3 syncope, 2 VF) as LQTS patients, while the QTc interval was shorter in patients with RyR2 mutation than those with genotype-negative LQTS (441±32 vs. 487±47ms; p=0.01). Conclusions: These findings suggest that CaM interacting genes have an important role on the pathogenesis of LQTS. In particular, RYR2 mutations may cause an overlap syndrome between catecholaminergic polymorphic ventricular tachycardia and LQTS.

Mutations in Conserved Amino Acids in the KCNQ1 Channel and Risk of Cardiac Events in Type-1 Long-QT Syndrome

2009 ◽  
Vol 20 (8) ◽  
pp. 859-865 ◽  
Author(s):  
CHRISTIAN JONS ◽  
ARTHUR J. MOSS ◽  
COELI M. LOPES ◽  
SCOTT MCNITT ◽  
WOJCIECH ZAREBA ◽  
...  
Keyword(s):  
Amino Acids ◽  
Long Qt Syndrome ◽  
Cardiac Events ◽  
Long Qt ◽  
Qt Syndrome ◽  
Conserved Amino Acids

scholarly journals A novel KCNH2 frameshift mutation (c.46delG) associated with high risk of sudden death in a family with congenital long QT syndrome type 2

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hyun Sok Yoo ◽  
Nancy Medina ◽  
María Alejandra von Wulffen ◽  
Natalia Ciampi ◽  
Analia Paolucci ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Long Qt Syndrome ◽  
Cardiac Death ◽  
Frameshift Mutation ◽  
Alpha Subunit ◽  
Syndrome Type ◽  
Long Qt ◽  
Qt Syndrome ◽  
Congenital Long Qt Syndrome

Abstract Background The congenital long QT syndrome type 2 is caused by mutations in KCNH2 gene that encodes the alpha subunit of potassium channel Kv11.1. The carriers of the pathogenic variant of KCNH2 gene manifest a phenotype characterized by prolongation of QT interval and increased risk of sudden cardiac death due to life-threatening ventricular tachyarrhythmias. Results A family composed of 17 members with a family history of sudden death and recurrent syncopes was studied. The DNA of proband with clinical manifestations of long QT syndrome was analyzed using a massive DNA sequencer that included the following genes: KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, ANK2, KCNJ2, CACNA1, CAV3, SCN1B, SCN4B, AKAP9, SNTA1, CALM1, KCNJ5, RYR2 and TRDN. DNA sequencing of proband identified a novel pathogenic variant of KCNH2 gene produced by a heterozygous frameshift mutation c.46delG, pAsp16Thrfs*44 resulting in the synthesis of a truncated alpha subunit of the Kv11.1 ion channel. Eight family members manifested the phenotype of long QT syndrome. The study of family segregation using Sanger sequencing revealed the identical variant in several members of the family with a positive phenotype. Conclusions The clinical and genetic findings of this family demonstrate that the novel frameshift mutation causing haploinsufficiency can result in a congenital long QT syndrome with a severe phenotypic manifestation and an elevated risk of sudden cardiac death.

scholarly journals Who Is at Risk for Cardiac Events in Young Patients With Long QT Syndrome?

2003 ◽  
Vol 67 (12) ◽  
pp. 1007-1012 ◽  
Author(s):  
Masao Yoshinaga ◽  
Masami Nagashima ◽  
Toshimitsu Shibata ◽  
Ichiro Niimura ◽  
Mitsuo Kitada ◽  
...  
Keyword(s):  
At Risk ◽  
Long Qt Syndrome ◽  
Young Patients ◽  
Cardiac Events ◽  
Long Qt ◽  
Qt Syndrome
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