Multiple Clinical Manifestations of a Single SCN5A Mutation

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.