Heterozygous activating mutations in the gene encoding for the ATP-sensitive 
potassium channel subunit Kir6.2 (KCNJ11) have recently been shown to be a 
common cause of permanent neonatal diabetes. Kir6.2 is expressed in muscle, 
neuron and brain as well as the pancreatic beta-cell, so patients with KCNJ11 
mutations could have a neurological phenotype in addition to their diabetes. It 
is proposed that some patients with KCNJ11 mutations have neurological features 
that are part of a discrete neurological syndrome termed developmental Delay, 
Epilepsy and Neonatal Diabetes (DEND), but there are also neurological 
consequences of chronic or acute diabetes. We identified KCNJ11 mutations in 
four of 10 probands with permanent neonatal diabetes and one affected parent; 
this included the novel C166F mutation and the previously described V59M and 
R201H. Four of the five patients with mutations had neurological features: the 
patient with the C166F mutation had marked developmental delay, severe 
generalised epilepsy, hypotonia and muscle weakness; mild developmental delay 
was present in the patient with the V59M mutation; one patient with the R201H 
mutation had acute and chronic neurological consequences of cerebral oedema and 
another had diabetic neuropathy from chronic hyperglycaemia. In conclusion, the 
clinical features in these patients support the existence of a discrete 
neurological syndrome with KCNJ11 mutations. The severe DEND syndrome was seen 
with the novel C166F mutation and mild developmental delay with the V59M 
mutation. These features differ markedly from the neurological consequences of 
acute or chronic diabetes.