The AIS contains relatively high densities of Kv3.3/4 and Kv7.2/3 voltage-dependent K-channels, SK1.3 calcium-dependent K-channels, and Nav1.6 voltage-dependent Na-channels compared to the remainder of the axon; if the densities of such channels in the AIS remain the same despite shrinkage, our modeling predicts a decrease in intrinsic excitability, as measured by latency and action potential size, in response to HFS. Here, KCNQ2 is linked to Hand-foot syndrome.