Work

Brugada Syndrome: New Implications for Heterozygous Carriers of the Pathogenic SCN5A c. 689T >C(p. Ile230Thr ) Variant

Year: 2026

Type: article

Abstract: Pathogenic variants in the SCN5A gene and its subunits have been identified in individuals with Brugada Syndrome. One such SCN5A variant, c.689T>C(p.Ile230Thr), was previously reported as disease-causing only in homozygous individuals, with heterozygous carriers being unaffected. Presently, we discuss the case of an adolescent patient who presented for further evaluation of pre-syncopal episodes with ECG findings consistent with Brugada pattern who on further genetic evaluation was found to be a heterozygous carrier of the pathogenic SCN5A c.689T>C(p.Ile230Thr) variant. This unique case allows us to think differently about heterozygous carriers for this specific mutation, and while the risk for developing a life-threatening arrhythmia may be low, heterozygous carriers may benefit from clinical monitoring to reduce the potential for adverse cardiac outcomes. A 17-year-old male presented after a pre-syncopal episode whose ECG demonstrated sinus bradycardia and type 1 Brugada pattern. Genetic testing revealed this patient to be a heterozygous carrier of a pathogenic SCN5A variant (c.689T>C(p.Ile230Thr)) which was also found in his father and brother, neither of whom had symptoms but did have ECG changes. He was diagnosed with Brugada Syndrome and advised to avoid known triggers. This case highlights the potential risk of severe cardiac arrhythmias in heterozygous carriers of the SCN5A c.689T>C (p.Ile230Thr) variant, previously thought to be benign. The 17-year-old patient, along with his asymptomatic father and brother who also carried the variant, exhibited ECG changes consistent with Brugada pattern. This finding suggests that heterozygous carriers may require closer monitoring and early intervention to prevent future life-threatening cardiac events.

Source: American Journal of Medical Genetics Part A

DOI: 10.1002/ajmga.70033

Authors: Shayla Shojaat, Benjamin Hale, Taylor Warner

Institution: University of Iowa

Language: English

Topic: Cardiac electrophysiology and arrhythmias

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,710