title: Patients with KCNJ11-related diabetes frequently have neuropsychological impairments compared with sibling controls.
abstract: KCNJ11-related diabetes is the most common form of permanent neonatal diabetes and has been associated with a spectrum of neurodevelopmental problems. We compared neurodevelopmental outcomes in patients with KCNJ11 mutations and their sibling controls.
  
  
  
  Through our Monogenic Diabetes Registry (http://monogenicdiabetes.uchicago.edu/), we evaluated 23 patients with KCNJ11 mutations with (n = 9) and without (n = 14) global developmental delay successfully treated with sulfonylurea and 20 healthy sibling controls, using a battery of targeted neuropsychological and behavioural assessments with scaled scores that are comparable across a wide range of ages.
  
  
  
  Patients with KCNJ11-related diabetes without global developmental delay had significant differences compared with sibling controls on a range of assessments including IQ, measures of academic achievement and executive function. KCNJ11 patients with global delay exhibited significant differences in behavioural symptoms with a tendency to avoid social contact and displayed a reduced ability to adapt to new circumstances. Parents reported more immature behaviour, gross mood swings, bizarre thoughts, other unusual and severe behaviours, and there were also significant deficits in all subdomains of daily living skills.
  
  
  
  This series represents the largest and most comprehensive study of neuropsychological and behavioural dysfunction of individuals with KCNJ11 diabetes and is the first to compare outcome with sibling controls. Our data demonstrate the variety of neurodevelopmental problems seen in those with KCNJ11 mutations, even in those without recognized global developmental delays. These data can be used to counsel families and guide structured neurodevelopmental assessments and treatments based on the initial genetic diagnosis in patients with neonatal diabetes.
authors.affiliation: Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, USA.
authors.forename: D
authors.initials: D
authors.lastname: Carmody
authors.affiliation: Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, USA.
authors.forename: A N
authors.initials: AN
authors.lastname: Pastore
authors.affiliation: Kennedy Research Center on Intellectual and Developmental Disabilities, Section of Developmental and Behavioral Pediatrics, The University of Chicago, Chicago, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Landmeier
authors.affiliation: Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, USA.
authors.forename: L R
authors.initials: LR
authors.lastname: Letourneau
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, USA.
authors.forename: R
authors.initials: R
authors.lastname: Martin
authors.affiliation: Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Hwang
authors.affiliation: Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, USA.
authors.forename: R N
authors.initials: RN
authors.lastname: Naylor
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Hunter
authors.affiliation: Kennedy Research Center on Intellectual and Developmental Disabilities, Section of Developmental and Behavioral Pediatrics, The University of Chicago, Chicago, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Msall
authors.affiliation: Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, USA.
authors.forename: L H
authors.initials: LH
authors.lastname: Philipson
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, USA.
authors.forename: M N
authors.initials: MN
authors.lastname: Scott
authors.affiliation: Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, USA. sgreeley@uchicago.edu.
authors.forename: S A W
authors.initials: SA
authors.lastname: Greeley
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D003920:Diabetes Mellitus / Q000145:classification / Q000235:genetics* / Q000523:psychology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000235:genetics / Q000523:psychology; D008297:Male; D020125:Mutation, Missense; D009461:Neurologic Manifestations; D009483:Neuropsychological Tests; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D035781:Siblings; D000099161:Kcnj11 Channel
chemical_list: D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel