This series of posts regarding Brugada Syndrome (BrS) started due to my recent literature search and reading up on the disease. Following recent discussions regarding the disease with co-workers that are experts on genetics, I've been slowly reminded of the fascinating genetic causes of the disease.

My personal interests however, are more interested in the electrophysiology/mechanism of disease. As previously mentioned, a large proportion of affected individuals have mutations in the SCN5A voltage-gated sodium channel, although many other genes are being implicated. A recent editorial by Viskin in Circulation is a great read I would recommend. The disease is rare, and Viskin analyzes the current approach for care provided to children with the disease with what I believe is an important discussion regarding treatment options, considering that many children with BrS are asymptomatic.

One aspect of the disease that I recently found interesting was gender differences. BrS is known to be a genetic disorder with an autosomal dominant pattern of inheritance, therefore we would expect males and females to be equally likely to inherit a defective gene from the parent. The quite fascinating aspect however, is that the majority of carriers of the disease who actually develop arrhythmias or other symptoms are later in adulthood (mean age of 34-53 years) and also >90% male.

Based on the reported mechanism and greater proportion of affected males, there are reports hypothesizing hormonal changes (specifically related to testosterone which would exacerbate the sodium channel defect) during puberty to account for this apparent inequality in gender.

The story becomes quite interesting when we consider the gender distribution in paediatric populations. Probst and colleagues reported no obvious male predominance among symptomatic or asymptomatic children with BrS in a sample of 30 children and adolescents (less than or equal to 16 years of age). This supports the proposed model of disease progression being linked to hormonal changes during puberty, as a paediatric population would not have undergone these changes in testosterone levels resulting in an equal distribution of males and females.

This is a bit of a sidetrack from Brugada Syndrome (BrS) and BrS in children specifically.

Through my work at The Hospital for Sick Children, one organization that I have been exposed to indirectly is the SADS Foundation. SADS stands for Sudden Arrhythmia Death Syndromes, an organization which focuses on the types of rhythm disorders that I am involved with through my work at SickKids.

Sudden cardiac death (which in certain diseases is associated with exercise specifically) is a concern for a number of arrhythmias/other arrhythmogenic diseases. It is quite unfortunate that due to the risk of death, it is not the best clinical symptom to screen for. This is why a number of preventative measures are important, and the emerging use of exercise stress tests in patient diagnosis in addition to preventative treatments such as ICD implant.

For more on SADS check out the following links:

http://www.sads.ca/
http://www.sads.org/What-is-SADS/Brugada-Syndrome

As I continued my literature review/readings into Brugada Syndrome (BrS) I came across quite the unique image.

Although diagnosis of BrS is a complex process involving various electrophysical tests to provide a conclusive diagnosis, one general "hallmark" of the disease is ST-segment elevation in the right precordial leads (V1-V3). I came across a powerpoint presentation which included BrS (link provided at the end of this post).

This person simply concluded that "Brugada = Sailboat of Death in Leads V1-V3)", as the large ST segment elevation could visually be similar in appearance to the sails on a sailboat. What a random, yet interesting little analogy. Now whenever I see a sailboat on the open water, I will be reminded of Brugada!

http://www.slideshare.net/islamghanem/brugada-casepresentation [SLIDE 9]
Islam Ghanem -Assistant lecturer of cardiology-Zagazig

I thought I'd start off my first official blog post with something I've been working on for the past few weeks. I recently analyzed a data set that had to do with ECG parameters in Brugada Syndrome (BrS) in a paediatric population. Although I cannot share details regarding my dataset specifically as the results of my analysis/the dataset are not published, just conducting background reading on this disease opened my eyes to a disease that is rare and as you can therefore guess not widely known among the general public. Since there is so much I could discuss from all of my readings, I will split this up into multiple posts.

Brugada Syndrome (BrS) is an inherited cardiac disorder, first identified by the Brugada brothers in 1992 to be a clinically distinct syndrome. Patients with BrS are at risk for sudden cardiac death, with generally no observed structural abnormalities observed in the heart. BrS is classically characterized by ST segment elevation in leads V1-V3 (for more review papers/background see some sample references below). Overall, the mechanism for disease progression is largely associated with mutations in the SCN5A sodium voltage gated channel.

This is a quick background on this rare disease. After reading these kinds of reviews for the disease as a whole, my focus shifted towards reports on paediatric BrS due to the research questions associated with the dataset I was working with. Stay tuned for more on how the story becomes quite interesting when we consider reports of BrS in children, and how the disease isn't identical as we know it in adults!

• Berne, P., & Brugada, J. (2012). Brugada syndrome 2012. Circulation Journal, 76(7), 1563-1571.
• Brugada, P., Brugada, R., & Brugada, J. (2000). The Brugada syndrome. Current Cardiology Reports, 2(6), 507-514.
• Brugada, P., & Brugada, J. (1992). Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome: a multicenter report. Journal of the American College of Cardiology, 20(6), 1391-1396.