OBJECTIVES: Activating mutations in the human KCNJ11 gene, encoding the 
pore-forming subunit (Kir6.2) of the ATP-sensitive potassium (K(ATP)) channel, 
are one cause of neonatal diabetes mellitus. In a few patients, KCNJ11 mutations 
cause a triad of developmental delay, epilepsy, and neonatal diabetes (DEND 
syndrome). The aim of this study was to determine the clinical effects, 
functional cause, and sensitivity to sulfonylurea treatment of a novel KCNJ11 
mutation producing DEND syndrome.
METHODS: We screened the DNA of a 3-year-old patient with neonatal diabetes, 
severe developmental delay, and therapy-resistant epilepsy for mutations in 
KCNJ11. We carried out electrophysiologic analysis of wild-type and mutant 
K(ATP) channels heterologously expressed in Xenopus oocytes.
RESULTS: We identified a novel Kir6.2 mutation (I167L) causing DEND syndrome. 
Functional analysis showed both homomeric and heterozygous mutant channels were 
less inhibited by MgATP leading to an increase in whole-cell K(ATP) currents. 
This effect was due to an increase in the intrinsic open probability. 
Heterozygous channels were strongly inhibited by the sulfonylurea tolbutamide. 
Treatment of the patient with the sulfonylurea glibenclamide not only enabled 
insulin therapy to be stopped, but also resulted in improvement in epilepsy and 
psychomotor abilities.
CONCLUSIONS: We report a case of developmental delay, epilepsy, and neonatal 
diabetes (DEND) syndrome that shows neurologic improvement with sulfonylurea 
therapy. Early recognition of patients with DEND syndrome may have considerable 
therapeutic benefit for the patient.