Resum

In this work we have investigated the Brugada syndrome caused by mutations in the sodium channel. We have performed clinical and genetic investigations to identify the genetic carriers. We have also investigated how the genetic background and the external modifiers modulate the disease phenotype. We have been able to prove that in Brugada syndrome the genetic testing is very valuable for two main reasons: first, because in a family with an identified mutation we are able to identify the non-carriers, and therefore those that are free of the disease. Secondly genetic testing allows the adoption of preventive measures in asymptomatic carriers, like the rapid treatment of fever or the avoidance of drugs that may block the sodium channel. Only for those two reasons it is justifiable the genetic analysis. Finally we have shown that neither the type of mutation, nor its localization in the protein allows us to estimate the risk of sudden death. In the asymptomatic individual with a normal ECG, the presence of a mutation is only indicative of a risk of developing the disease, but it is not a given that he will suffer from it. Despite the increase in genetic testing, at present its practice does not seem justified if only to define the therapeutic aggressiveness. The asymptomatic individuals who develop symptoms at follow-up present always clear clinical alterations, like a prolongation of the QT interval or elevation of the ST segment. These ecg parameters already define the need to perform additional tests or the adoption of preventive measures. In conclusion, being only a genetic carrier does not justify a more aggressive treatment at present. The treatment has to be determined by the result of the clinical tests.

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