In contrast, gain of channel function has been linked to other specific disease entities, such as long QT syndrome.3,8,9 More severe phenotypes, such as congenital SSS, can be caused by more severe LoF of the channel, for instance through the presence of 2 defective SCN5A alleles.10–12 Genetically caused SCN5A LoF is comparable to sodium channel blocker medications, which are used to mediate a desirable LoF effect, but may also increase risk of cardiac arrhythmias in certain contexts. Here, SCN5A is linked to cardiac arrhythmia.