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.
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.