Ventricular fibrillation in Graves disease reveals a rare SCN5A mutation with W1191X variant associated with Brugada syndrome

Stawiarski, Kristin; Clarke, John‐Ross D.; Pollack, Ari; Winslow, Robert; Majumdar, Sachin

doi:10.1016/j.hrcr.2020.11.010

Cited by 5 publications

(5 citation statements)

References 15 publications

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“…An ECG that was performed after she was re-admitted for fever and pleural effusion exhibited the type 2 BrS ECG pattern, although the report is unclear whether she performed ECG at the time of the actual fever. Genetic testing revealed a likely pathogenic mutation in the SCN5A gene (130). Therefore, genetic studies could be helpful to better understand the link between the manifestation of the BrS ECG pattern and thyroid dysfunction.…”

Section: Brugada Syndrome and Thyroid Dysfunctionmentioning

confidence: 99%

Brugada Syndrome: Warning of a Systemic Condition?

D'Imperio

Monasky

Micaglio

et al. 2021

Front. Cardiovasc. Med.

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Brugada syndrome (BrS) is a hereditary disorder, characterized by a specific electrocardiogram pattern and highly related to an increased risk of sudden cardiac death. BrS has been associated with other cardiac and non-cardiac pathologies, probably because of protein expression shared by the heart and other tissue types. In fact, the most commonly found mutated gene in BrS, SCN5A, is expressed throughout nearly the entire body. Consistent with this, large meals and alcohol consumption can trigger arrhythmic events in patients with BrS, suggesting a role for organs involved in the digestive and metabolic pathways. Ajmaline, a drug used to diagnose BrS, can have side effects on non-cardiac tissues, such as the liver, further supporting the idea of a role for organs involved in the digestive and metabolic pathways in BrS. The BrS electrocardiogram (ECG) sign has been associated with neural, digestive, and metabolic pathways, and potential biomarkers for BrS have been found in the serum or plasma. Here, we review the known associations between BrS and various organ systems, and demonstrate support for the hypothesis that BrS is not only a cardiac disorder, but rather a systemic one that affects virtually the whole body. Any time that the BrS ECG sign is found, it should be considered not a single disease, but rather the final step in any number of pathways that ultimately threaten the patient's life. A multi-omics approach would be appropriate to study this syndrome, including genetics, epigenomics, transcriptomics, proteomics, metabolomics, lipidomics, and glycomics, resulting eventually in a biomarker for BrS and the ability to diagnose this syndrome using a minimally invasive blood test, avoiding the risk associated with ajmaline testing.

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Section: Brugada Syndrome and Thyroid Dysfunctionmentioning

confidence: 99%

Brugada Syndrome: Warning of a Systemic Condition?

D'Imperio

Monasky

Micaglio

et al. 2021

Front. Cardiovasc. Med.

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“…Although these patients typically do not show ventricular tachycardia or TdP, hypothyroidism exacerbates the arrhythmogenic risk in BrS, especially in those with SCN5A mutations. These mutations, coupled with thyroid conditions such as thyrotoxicosis ( 18 ) or hypothyroidism ( 19 ), increase the likelihood of ventricular arrhythmias in this high-risk group. Thus, thyroid states can crucially influence SCN5A function, heightening the arrhythmogenic potential in BrS patients.…”

Section: Discussionmentioning

confidence: 99%

A Pediatric Case of Refractory Torsades de Pointes in Autoimmune Hypothyroidism

Chimatapu,

Schachter,

Batra

et al. 2024

JCEM Case Reports

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Hypothyroidism can have a significant impact on cardiac contractility, vascular resistance, blood pressure, and cardiac rhythm. Ventricular arrhythmias induced by hypothyroidism are infrequently reported, especially in pediatric cases. A 15-year-old girl with autoimmune hypothyroidism experienced pulseless ventricular arrhythmias on 2 separate occasions because of nonadherence to levothyroxine medication. Subsequent investigations revealed an SCN5A mutation associated with Brugada syndrome. A loop recorder captured polymorphic ventricular tachycardia (PMVT), specifically Torsades de Pointes during her second event. Both arrhythmias were addressed only after stabilizing her thyroid hormone levels with replacement therapy. Although rare, patients with uncontrolled hypothyroidism may present with ventricular arrhythmias, particularly PMVT. The cornerstone of treatment for hypothyroidism-induced ventricular arrhythmia is thyroid replacement therapy. The identification of an SCN5A mutation unmasked by overt hypothyroidism emphasizes the need for a comprehensive cardiac evaluation in patients with hypothyroidism being assessed for PMVT.

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“…In patients with a genetic predisposition for arrhythmias, thyrotoxicosis can lower the arrhythmia threshold, and in rare cases, ventricular fibrillation may occur. A recent case report described a patient carrying the SCN5A mutation who developed ventricular fibrillation in the setting of hyperthyroidism [25]. SCN5A mutations have been implicated in the pathogenesis of long QT syndrome, BrS, and cardiomyopathy [26].…”

Section: Discussionmentioning

confidence: 99%

“…Nav1.5, the pore forming α-subunit of the voltage-dependent cardiac Na+ channel, is not exclusively expressed in heart but has also been detected in the brain and gastrointestinal smooth muscle [27]. It has been reported that SCN5A-mediated abnormal cardiac phenotypes overlap with epilepsy [28][29][30], hyperthyroidism [25], and irritable bowel syndrome. Thus, some researchers propose concepts of overlap syndromes and systemic disorders in relation to SCN5A-mediated cardiac disfunctions [31].…”

Section: Discussionmentioning

confidence: 99%

Pathogenic SCN5A Mutation and Thyrotoxicosis-Related Neurological Syndrome: Casual or Causal Relationship?

Zhao

Jiang

et al. 2023

Brain Sciences

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Background: Various neurologic complications of hyperthyroidism are reported, and most of these complications are reversible with the amelioration of thyrotoxicosis. We report a previously undescribed concurrence of hyperthyroid-associated exercise-induced myalgia and stiffness, pyramidal tract dysfunction, and myoclonic movements that make an initial clinical diagnosis difficult. Case presentation: A 17-year-old male was hospitalized in the department of neurology, presenting with a 4-year history of severe exercise-induced myalgia and stiffness, weakness of lower limbs, and myoclonic movements. Laboratory investigations unexpectedly revealed hyperthyroidism. MRI of the brain and spine, electrophysiology, and whole exome sequencing were also performed. Antithyroid therapy led to marked improvement of neurologic symptoms, accompanied by a significant improvement of the time-dependent decline in compound muscle action potentials (CMAP) amplitudes after exercise and normalization of the prolonged QTc interval. Genetic analysis identified a rare variant in SCN5A. Conclusion: This case report provides important insights into the relationship between hyperthyroidism and neurologic/cardiac complications, particularly in those with a genetic predisposition. SCN5A mutation possibly plays a role in the complex neurological syndrome associated with hyperthyroidism. Further studies are warranted to better understand the underlying mechanisms and potential therapeutic options for these complex conditions.

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Ventricular fibrillation in Graves disease reveals a rare SCN5A mutation with W1191X variant associated with Brugada syndrome

Cited by 5 publications

References 15 publications

Brugada Syndrome: Warning of a Systemic Condition?

Brugada Syndrome: Warning of a Systemic Condition?

A Pediatric Case of Refractory Torsades de Pointes in Autoimmune Hypothyroidism

Pathogenic SCN5A Mutation and Thyrotoxicosis-Related Neurological Syndrome: Casual or Causal Relationship?

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