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May 19, 2026Journal of the American College of Cardiology

Genotype-phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non–SCN5A-related patients

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Why the study?

SCN5A mutations are found in only a minority of Brugada syndrome patients, and establishing a genotype-phenotype relationship might facilitate screening.

Does the presence of an SCN5A mutation in Brugada syndrome patients correlate with specific clinical or electrocardiographic features compared to non-carriers?

Population

Brugada syndrome patients with (n = 23) or without (n = 54) an identified SCN5A mutation

Comparison

SCN5A mutation carriers vs non-carriers

Design

Multicenter study

Key result

Brugada syndrome patients with an SCN5A mutation had significantly longer baseline PQ and HV intervals compared to non-carriers, with PQ ≥210 ms and HV ≥60 ms predictive of mutation presence.

Authors

JSJ SMITSLELars EckardtVPVincent Probst

Discussion

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Overview

May aid noninvasive SCN5A prediction in Brugada syndrome; extends genotype-phenotype correlations while leaving management implications open.

Key Points

  • This research aims to explore how genotype affects phenotype in Brugada syndrome, focusing on the differences between SCN5A and non-SCN5A genetic variants.
  • Analyzed electrocardiographic features of patients with Brugada syndrome
  • Compared SCN5A-related patients with non-SCN5A-related patients
  • Used statistical analyses to assess differences in ECG characteristics
  • Significant differences in electrocardiographic features between SCN5A and non-SCN5A patients
  • Higher prevalence of specific ECG patterns in SCN5A-related cases
  • Findings support the role of genetic testing in guiding clinical management

Study Design

Type

Observational (n=77)

Multicenter

Yes

Structured PICO

Does the presence of an SCN5A mutation in Brugada syndrome patients correlate with specific clinical or electrocardiographic features compared to non-carriers?

P
Population
77 patients with Brugada syndrome, comprising those with (n=23) and without (n=54) an identified SCN5A mutation.
I
Intervention
Presence of SCN5A mutation (carriers) and pharmacologic challenge with I(Na) blocking drugs
C
Comparator
Absence of SCN5A mutation (non-carriers)
O
Outcome
Differences in ECG parameters (PQ interval, QRS duration), His to ventricle (HV) interval, demographics, and clinical/family historysurrogate

Brugada syndrome patients with an SCN5A mutation exhibit significantly longer conduction intervals on baseline ECG and after sodium channel blockade, allowing for phenotypic differentiation from non-carriers.

Cite This Study

SMITS et al. (2002) conducted an observational in Brugada syndrome (n=77). SCN5A mutation (carriers) vs. No SCN5A mutation (non-carriers) was evaluated on Electrocardiographic parameters including PQ interval and HV time. Brugada syndrome patients with an SCN5A mutation had significantly longer baseline PQ and HV intervals compared to non-carriers, with PQ ≥210 ms and HV ≥60 ms predictive of mutation presence.

synapsesocial.com/papers/6a0cd3b42a25805b8ff6fd54https://doi.org/10.1016/s0735-1097(02)01962-9
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1A study of the SCN5A gene in a cohort of 76 patients with Brugada syndrome2012 · 18 citations
  2. 2Brugada syndrome genetics is associated with phenotype severity2020 · 106 citations
  3. 3Progressive Cardiac Conduction Defect is the Prevailing Phenotype in Carriers of a Brugada Syndrome <i>SCN5A</i> Mutation2006 · 115 citations
  4. 4The SCN5A Gene Is a Predictor of Phenotype Severity in Brugada Syndrome: A Comprehensive Literature Review2022 · 7 citations
  5. 5Brugada syndrome: clinical presentation and genotype—correlation with magnetic resonance imaging parameters2015 · 48 citations