So the correct answer is C, incomplete penetrance. Carrier testing of Frank is appropriate as he is first degree relative of his father who has Brugada syndrome. Now Frank did not carry the mutation that his father has, but Frank's ECG has a spontaneous type 1 Brugada pattern so he also has Brugada syndrome. Note that symptoms are not necessary to get the diagnosis of Brugada syndrome. Now unlike most of the other inherited arrhythmia syndromes that we talk about, Brugada syndrome is known to be polygenic. Thus his father may carry multiple genetic mutations in variants and he may have transmitted a different one that we didn't identify by genetic testing to Frank, causing Brugada syndrome in Frank. Now Frank could have a different biological father than his perceived father and it could be a coincidence that both he and his father have Brugada syndrome. Unlikely as Brugada syndrome is only present in 1 in 2,000 to 1 in 5,000 in the population, but possible. Genetic testing and mutant identification is far from perfect. It's possible that the SCN5A variant identified in Frank's father is not pathogenic and that both he and his father share an unidentified Brugada syndrome mutation or more than one mutation. Finally, while incomplete penetrance is common, it does not explain the presence of a disease phenotype in both Frank and his father. Incomplete penetrance would be present if Frank had the mutation but had a normal electrocardiogram.

Brugada syndrome

spontaneous ECG pattern

genetic factors

mutation inheritance

carrier testing