The Genetics of Brugada Syndrome
Brief bio and areas of interest
Dr. Lubitz’s bio on massgeneral.org states, “Dr. Lubitz graduated from the University of Michigan Medical School. He trained in internal medicine and cardiovascular disease at Mount Sinai Hospital in New York, where he also served as a Chief Medical Resident. Dr. Lubitz earned a Master of Public Health degree from the Harvard University School of Public Health. He completed his clinical electrophysiology training at the Massachusetts General Hospital.”1
He is interested in the genetics of electrophysiology because he gets to see how genetics has unlocked keys to understanding the biological mechanisms of disease. He enjoys the blending of clinical work and research. In addition to Brugada Syndrome, he focuses on arrhythmia syndromes such as atrial fibrillation, slow heart rates, supraventricular tachycardias, ventricular arrhythmias, and more.
Below is a portion of the conversation, focused on the genetics of Brugada Syndrome.
Could you tell me a little bit about the history of the discovery of Brugada Syndrome?
It's an interesting condition because most people with a Brugada pattern won't ever have an adverse cardiac event. For years the pattern on the EKG was sort of regarded as a normal variant on the ECG (electrocardiogram).
Then around the 1990s, reports started to emerge about the risk of dangerous arrhythmias among people who had these ECG patterns. The Brugada brothers described the series of patients in whom this pattern was noted as well, who had had a cardiac arrest, so thereafter the ECG pattern was coined “Brugada Syndrome” or the “Brugada pattern.”
In the 1990s, genetic mapping really started to take hold in humans. Ultimately, a number of different approaches were employed to try to get at the genetic basis of Brugada syndrome, which remains an area of very active research at the moment. We recognize the condition is heritable.
But the one gene that has really kind of stood out the most is this gene called SCN5A, which is more or less the electrical workhorse of the heart. It's a ubiquitous gene and it makes a protein that is involved in creating a sodium channel, so a channel that carries sodium molecules back and forth across the cardiac cellular membrane.
Do we know how common Brugada syndrome is in the general population?
What I can say is that it's rare, but we don't have a really accurate denominator. This is because the pattern can come and go in a lot of people, and we only have EKGs that are 10 seconds long to measure it. But it's estimated clinically that it's far less than 1%. So it's a relatively rare condition, and as far as inherited arrhythmia syndromes go, it's not among the most common, but it is something that we see quite often, particularly in our field.
How many people who are diagnosed with Brugada Syndrome have an identifiable gene mutation at the moment?
The SCN5A gene mutations, which are just genetic variants that we think could be responsible, are detected in about 20 to 30% of people who have the diagnostic pattern on the ECG.
Do you think with all of the self-monitoring that we do now with technology, that there might be a future in which people have an ECG going 24/7?
Things are clearly moving that way. Though whether that will turn into increased frequency of diagnoses of Brugada Syndrome or not, I have no idea, because it turns out you have to have the right ECG lead in the right place at the right time.
Do you see genetics playing a role in the future treatment of Brugada right now? One of the biggest treatments is an ICD, but do you think there'll be a cure or a better treatment?
I hope so. I think ICDs are great at doing what they're designed to do, but they don't treat the underlying condition. I'm hopeful that through genetics, we could learn the biological underpinnings of the condition and the pathways involved, and then we can start to think about what therapeutics might be most appropriate considering what we know now about the biology. Only a few years ago we knew a whole lot less than we know now.
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