Documented Sudden Cardiac Death in Prolonged QT Syndrome

Using a clinical example, the article draws the attention of doctors to the problem of the prolonged QT interval (long QT) and the related problem of fainting (syncope). Syncope is a component of long QT syndrome, and syncope is a precursor of sudden cardiac death. However, syncope in a patient with long QT syndrome may have pathogenesis that is completely unrelated to abnormalities of cardiac ion channels. In other words, such a patient may have a second disease as a syntropy relates to prolonged QT interval, to an extent mimicking long QT syndrome. The presented medical history of a 33-year-old patient S. shows the complexity of differential diagnosis of the causes of syncope. The crucial part in the diagnosis, in addition to the clinical picture, was the so-called tilt test, little-known to general medical practice, as well as the laboriousness of making a final diagnosis of the long QT Syndrome type 2, which required a molecular genetic study whole-exome sequencing. Patient S. had vasovagal syncope that not associated with long QT syndrome, but she has a risk of sudden cardiac death, and the article identifies therapeutic and other measures to reduce this risk.

Download Full-text

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

International Journal of Arrhythmia ◽

10.1186/s42444-020-00029-1 ◽

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.

Download Full-text