Thus, mutations which alter channel opening cause defects in insulin secretion, for example mutations which enhanced PIP2 binding (such as K39R, E179A, E179K) are associated with neonatal diabetes (ND), whereas mutations which destabilise PIP2 binding (such as K67N) to the channel results in congenital hyperinsulinism (CHI) – an opposite phenotype.8, 42, 136, 137 Mutations to the PIP2 binding site of Kir2.1 (such as R218Q/W) are shown to be associated with Andersen-Tawil syndrome (ATS) which displays cardia arrythmia, periodic paralysis and dysmorphic features. Here, INS is linked to congenital isolated hyperinsulinism.