Multiple Clinical Manifestations of a Single SCN5A Mutation

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Background: The SCN5A-gene encodes for the cardiac sodium channel and has been associated with Long-QT syndrome, Brugada syndrome (BrS) and conduction disease. We investigated the clinical manifestations in families with the SCN5A F861WfsX90 mutation. Methods and Results: In total, 112 patients (53 males, 43±18 years, 56 mutation carriers) were included. Ten mutation carriers manifested with BrS (3 patients with a history of VT/VF, 4 with syncope and 4 asymptomatic patients), 4 carriers with cardiac conduction disease (one with a history of VF and 2 with syncope), 2 carriers with sick sinus syndrome and one carrier with VT. The non-carriers did not manifest any clinical phenotype. Conduction parameters of 12-lead ECG (>15 years old) were longer in the carriers than the non-carriers (P wave 131±16 vs. 106±13, PR interval 204±24 vs. 159±23, QRS width 111±21 vs. 89±16, respectively, P<0.001, QTc 407±33 vs. 412±28 (ms), P>0.05). Conclusions: Although F861WfsX90 is reported as a putative SCN5A mutation in BrS, only 17.8% (10/56) of the mutation carriers in our cohort showed BrS as a clinical phenotype. This knowledge has important implications for treatment and warrants further investigations for (genetic) modifiers of this SCN5A mutation.