[Long QT syndrome and Brugada syndrome: 2 aspects of the same disease?].
In clinical cardiology, resort has recently been made to molecular genetics in order to explain some mechanisms that underlie sudden cardiac death in young people with structurally normal hearts. It has become evident that genetic mutations regarding cardiac ion channels may disrupt the delicate balance of currents in the action potential, thus inducing malignant ventricular tachyarrhythmias. The cardiac sodium channel gene, SCN5A, is involved in two of such arrhythmogenic diseases, the Brugada syndrome and one form of the long QT syndrome (LQT3). It is believed that these syndromes result from opposite molecular effects: Brugada syndrome mutations cause a reduced sodium current, while LQT3 mutations are associated with a gain of function. The effects of class I antiarrhythmic drugs have been used to differentiate these diseases. Intravenous flecainide is used as a highly specific test to unmask the electrocardiographic phenotype of the Brugada syndrome. On the other hand, on the basis of experimental and clinical studies, the possibility that the same drugs act as a gene-specific therapy in this disorder by contrasting the effect of mutations in LQT3 has been explored. Recent evidence shows that phenotypic overlap may exist between the Brugada syndrome and LQT3. One large family with a SCN5A mutation and a "mixed" electrocardiographic pattern (prolonged QT interval and ST-segment elevation) has been reported. Moreover, our recent data showed that flecainide challenge may elicit ST-segment elevation in some LQT3 patients. The presence of "intermediate" phenotypes highlights a remarkable heterogeneity suggesting that clinical features may depend upon the single mutation. Only deepened understanding of the genotype-phenotype correlation will allow the definition of the individual patient's risk and the development of guidelines for clinical management.
Cerrone
M
M
Dipartimento di Cardiologia, IRCCS Policlinico San Matteo, Pavia.
Crotti
L
L
Faggiano
G
G
De Michelis
V
V
Napolitano
C
C
Schwartz
P J
PJ
Priori
S G
SG
D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D016757:Death, Sudden, Cardiac; D003937:Diagnosis, Differential; D006801:Humans; D008133:Long QT Syndrome / Q000175:diagnosis* / Q000188:drug therapy; D013575:Syncope / Q000175:diagnosis*; D013577:Syndrome
D000889:Anti-Arrhythmia Agents