What is the clinical evidence from this study?

Study design: Case Report. Population: Congenital long QT syndrome (n=2). Intervention: Genetic testing and ICD implantation.

What does this research mean for the field?

Heterozygous pathogenic variants in the KCNH2 gene can present as recurrent syncope and congenital long QT syndrome, which can be effectively diagnosed through genetic testing and managed with ICD implantation. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To report two cases of recurrent syncope linked to KCNH2 gene mutations in patients with congenital long QT syndrome.

May 3, 2026Open Access

Case Report: Two cases of recurrent syncope caused by KCNH2 gene mutation in congenital long QT syndrome

Key Result

Genetic testing identified heterozygous pathogenic variants in the KCNH2 gene in two female patients with recurrent syncope, leading to a diagnosis of congenital long QT syndrome and successful treatment with ICD implantation.

Key Points

To report two cases of recurrent syncope linked to KCNH2 gene mutations in patients with congenital long QT syndrome.
Clinical data collected included QT interval measurements and corrected QT interval calculations using the Bazett formula.
Genetic testing identified heterozygous pathogenic variants in both patients.
Bioinformatics tools predicted the pathogenicity of the observed mutations.
Both patients exhibited significant QT interval prolongation linked to their mutations.
Case 1 had a frameshift mutation (c.234_241dup, p.Gln81Leufs*38).
Case 2 had a missense mutation (c.1841C > T, p.Ala614Val).

Study Design

Type

Case Report (n=2)

Multicenter

Structured PICO

Population

2 patients with congenital long QT syndrome presenting with recurrent syncope

Intervention

Genetic testing

Outcome

Identification of pathogenic variants in the KCNH2 genesurrogate

Genetic testing successfully identified KCNH2 gene mutations in two patients with congenital long QT syndrome presenting with syncope, highlighting its role in diagnosis and personalized treatment.

Limitations

Small sample size of only two cases
Retrospective analysis

Abstract

This study presents two cases of congenital long QT syndrome caused by KCNH2 gene mutations. It highlights the critical role of genetic testing in its diagnosis and underscores the importance of early detection and personalized treatment strategies to enhance patient outcomes. Comprehensive clinical data were collected from the patients, including measurements of the QT interval and calculations of the corrected QT interval (QTc) using the Bazett correction formula. Genetic testing identified heterozygous pathogenic variants in the KCNH2 gene in both patients. The variant in Case 1 was a frameshift mutation (c. 234₂41dup, p. Gln81Leufs*38), located in exon 2 (NM₀00238. 4). Case 2 carried a missense mutation (c. 1841C > T, p. Ala614Val) in exon 7 (NM₀00238. 4). Predictions from multiple bioinformatics tools were consistent with the pathogenicity of both variants. The findings underscore that early diagnosis and tailored therapeutic approaches are essential for improving the prognosis of individuals with long QT syndrome. It is imperative for clinicians to increase awareness of long QT syndrome, particularly in patients presenting with syncope as an initial symptom, to inform clinical diagnosis, treatment, and prognostic assessment.

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