Related Experiment Video

Updated: Jan 10, 2026

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

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Clinical presentation and outcomes of patients with biallelic SCN5A variants: A systematic review

Elodie Surget1,2, Alexis Hermida3, Alice Maltret4

  • 1Reference Center for Inherited Arrhythmic Syndromes, Hôpital Bichat, APHP, Université Paris Cité, Paris, France.

Heart Rhythm O2
|November 24, 2025
PubMed

Insights

Biallelic SCN5A variants cause severe early-onset arrhythmias and high mortality. Non-missense variants are linked to worse outcomes, emphasizing the need for early diagnosis and management in this rare population.

Area of Science:

  • Genetics
  • Cardiology
  • Molecular Biology

Background:

  • Heterozygous SCN5A variants are linked to inherited arrhythmias.
  • Clinical phenotypes of biallelic (homozygous or compound heterozygous) SCN5A variants are poorly understood.

Purpose of the Study:

  • To systematically review clinical characteristics, outcomes, and genotype-phenotype correlations in patients with biallelic SCN5A variants.

Main Methods:

  • Systematic literature review of 33 articles involving 61 patients.
  • Evaluation of demographic data, medical history, prognosis, and genotype-phenotype correlations.

Main Results:

  • Most patients (81%) were symptomatic, presenting with syncope or cardiac arrest.
  • Sinus node dysfunction (65%) and progressive cardiac conduction disease (33%) were common phenotypes.
  • Non-missense variants correlated with earlier onset and increased risk of major cardiac events, with 50% experiencing major cardiac events and 15% dying young.

Conclusions:

  • Biallelic SCN5A variants lead to severe, early-onset arrhythmias with high morbidity and mortality.
  • Improved recognition and international collaboration are crucial for optimizing diagnosis and management.
  • Non-missense variants indicate a poorer prognosis, necessitating targeted interventions.
Abstract

Keywords:
Atrial standstillBrugadaSCN5AStrokeSudden death

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