# Case Report Series: Genetic and clinical characterization of long QT syndrome in admixed Ecuadorian patients and its implications for sudden cardiac death risk

## TL;DR

This paper reports three Ecuadorian patients with long QT syndrome, highlighting genetic variants and clinical features that help assess sudden cardiac death risk.

## Contribution

The study provides novel insights into LQTS in an admixed Ecuadorian population through detailed genetic and clinical analysis.

## Key findings

- Three Ecuadorian patients with LQTS were identified with distinct clinical features and pathogenic variants in KCNH2 or KCNQ1.
- Ancestry analysis enhanced genomic context for accurate diagnosis and personalized management of inherited arrhythmia syndromes.
- Integration of ECG findings, genetic testing, and ancestry-informed interpretation improved diagnostic accuracy in these cases.

## Abstract

Long QT syndrome (LQTS) is a hereditary cardiac channelopathy associated with delayed ventricular repolarization and increased risk of life-threatening arrhythmias and sudden cardiac death. We report three Ecuadorian patients with LQTS, each presenting distinct clinical features and carrying pathogenic or likely pathogenic variants in KCNH2 or KCNQ1. Subject A, an 18-year-old woman with exertion-related syncope and a QTc of 520 ms, was diagnosed with LQT2 due to a KCNH2 p.Ala614Val variant. Subject B, a 3-year-old girl with congenital deafness and a QTc of 580 ms, was diagnosed with Jervell and Lange-Nielsen syndrome (JLNS), harboring a homozygous KCNQ1 p.Arg192Cys variant. Subject C, a 44-year-old man with recurrent syncope misdiagnosed as epilepsy and a strong family history of sudden death, was found to carry a KCNH2 p.Val612Met variant and had a QTc of 600 ms. All variants were classified according to ACMG/AMP guidelines and supported by in silico and functional data. Ancestry analysis provided additional genomic context in this admixed population. These cases underscore the clinical utility of integrating ECG findings, genetic testing, and ancestry-informed interpretation to improve diagnostic accuracy and personalize management in patients with inherited arrhythmia syndromes.