The notion that SHE is a channelopathy is derived from early findings on mutations of nAChRs genes such as cholinergic receptor nicotinic alpha 2 subunit (CHRNA2), cholinergic receptor nicotinic alpha 4 subunit (CHRNA4) and cholinergic receptor nicotinic beta 2 subunit (CHRNB2) encoding for nAChRs containing subunits of α4β2 or heteromers with subunits of α2/β2/β4 (Figure 1) (Di Resta et al., 2010; Wallace and Bertrand, 2013; Becchetti et al., 2015). This evidence concerns the gene CHRNA4 and channelopathy.