# Unlocking the Secrets of Andersen–Tawil Syndrome: The Role of Next-Generation Sequencing in a Family With Long QT Syndrome

## TL;DR

This paper describes how next-generation sequencing identified a new genetic variant in a family with long QT syndrome and Andersen–Tawil syndrome.

## Contribution

A novel homozygous likely pathogenic KCNJ2 variant was identified in a patient with Andersen–Tawil syndrome.

## Key findings

- A novel homozygous likely pathogenic missense variant (c.G598A, p.V200M) in KCNJ2 was identified in the proband.
- Some family members were heterozygous for the variant but remained asymptomatic.
- NGS is proposed as a diagnostic tool for patients with dysmorphic and cardiac features.

## Abstract

Andersen–Tawil syndrome (ATS) is a rare inheritable potassium channelopathy, accompanied by ventricular arrhythmias due to long QT intervals, muscle weakness, and dysmorphic features. Next-generation sequencing can identify the genetic causes of the phenotype.

Whole-exome sequencing (WES) was performed on a 12-year-old girl with long QT syndrome and dysmorphic features. Sanger sequencing was subsequently used to confirm the variant and perform segregation analysis in the proband and all available family members.

WES identified a novel homozygous likely pathogenic missense variant (chr17, c.G598A, p.V200M; hg19; NM_017755.5) in KCNJ2 in the proband. Some of her family members were heterozygous for the variant but remained asymptomatic with no cardiac manifestation.

We propose that patients with dysmorphic skeletal findings and cardiac arrhythmias be evaluated via NGS for possible genetic variants.