title: ADHD, learning difficulties and sleep disturbances associated with KCNJ11-related neonatal diabetes.
abstract: OBJECTIVE
  Mutations in KCNJ11 are the most common cause of permanent neonatal diabetes mellitus (NDM). Approximately 25% of patients have obvious neurological dysfunction, but whether milder related problems might be more common has been unclear. We sought to assess the prevalence of parental concerns about learning, behavior, attention deficit hyperactivity disorder (ADHD), social competency, and sleep in subjects with KCNJ11-related NDM compared to unaffected sibling controls.
  
  
  METHODS
  Subjects or their guardians in the University of Chicago Monogenic Diabetes Registry completed a survey examining learning, behavior, ADHD and sleep. Thirty subjects with KCNJ11 -related NDM and 25 unaffected sibling controls were assessed. Data were analyzed using GraphPad Prism 6. Nonparametric analysis was performed using Fisher's exact test for group comparisons.
  
  
  RESULTS
  Thirteen (43%) individuals with KCNJ11 -related NDM had treatment for or a diagnosis of ADHD compared to two (8%) of the sibling controls (P < 0.05). Compared to their sibling controls, individuals with KCNJ11 mutations had significant differences in behavior difficulties, social awareness, academic achievement and the need for an Individualized Education Plan (IEP). As seen in other neurodevelopmental disorders, individuals with KCNJ11 mutations also had significantly higher rates of sleep difficulties (P < 0.01).
  
  
  CONCLUSIONS
  Patients with KCNJ11 -related NDM are at an increased risk for delays in learning, social-emotional and behavioral development, ADHD and sleep difficulties based on parent report. Early identification, along with integrated medical and developmental support, may promote better neurodevelopmental outcomes for this unique population. Further investigation utilizing detailed neuropsychological testing will better define the neurodevelopmental consequences of KATPmutations.
authors.affiliation: Section Department of Developmental and Behavioral Pediatrics, The University of Chicago, Chicago, Illinois.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Landmeier
authors.affiliation: Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, Illinois.
authors.forename: Monica
authors.initials: M
authors.lastname: Lanning
authors.affiliation: Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, Illinois.
authors.forename: David
authors.initials: D
authors.lastname: Carmody
authors.affiliation: Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, Illinois.
authors.forename: Siri Atma W
authors.identifier: http://orcid.org/0000-0002-0741-3567
authors.initials: SAW
authors.lastname: Greeley
authors.affiliation: Section Department of Developmental and Behavioral Pediatrics, The University of Chicago, Chicago, Illinois.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Msall
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D002641:Chicago / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006785:Hospitals, University; D006801:Humans; D007859:Learning Disabilities / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D007872:Legal Guardians; D008297:Male; D009154:Mutation; D010290:Parents; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D015995:Prevalence; D012042:Registries; D012306:Risk; D057566:Self Report; D035781:Siblings; D012893:Sleep Wake Disorders / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D000099161:Kcnj11 Channel
chemical_list: D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel
keywords: attention deficit disorder with hyperactivity; developmental disabilities; diabetes mellitus; genetics; permanent neonatal