title: Congenital central hypoventilation syndrome: neurocognitive functioning in school age children.
abstract: OBJECTIVE
  Examine indices of neurocognitive functioning in children with PHOX2B mutation-confirmed neonatal onset congenital central hypoventilation syndrome (CCHS) and relate them to indices of PHOX2B genotype, demographics, and disease severity.
  
  
  METHODS
  Subjects were 20 patients with PHOX2B mutation-confirmed CCHS diagnosed as neonates who had undergone neurocognitive assessment in the course of clinical care at the Rush Children's Hospital CCHS Center between 1990 and 2006. Neurocognitive variables of interest included Full Scale IQ (FSIQ) and Wechsler-derived marker indices (subtests) of verbal comprehension (Vocabulary), visuoperceptual reasoning (Block Design), working memory (Digit Span), and clerical/processing speed (Coding).
  
  
  RESULTS
  Single sample t-tests revealed participants' general intelligence index (FSIQ; mean 84.9, SD 23.6) to be lower than the general population, though the range of FSIQ observed was broad. Visuoperceptual reasoning and clerical/visuographic speed marker indices were similarly depressed. These deficits were related to special education participation but not to PHOX2B genotype status or other demographic and clinical risk factors.
  
  
  CONCLUSIONS
  PHOX2B mutation-confirmed CCHS confers risk for adverse neurocognitive outcome, though the range of functioning observed raises questions about factors that may contribute to neurocognitive variability. Visuoperceptual reasoning and clerical/visuographic speed appear particularly vulnerable. PHOX2B genotype and disease severity indicators were unrelated to neurocognitive indices, possibly due to our modest sample. Future research should employ comprehensive neurocognitive assessment emphasizing visuoperceptual ability, mental speed, attention, and information processing efficiency. Increased recognition and expedited diagnosis with PHOX2B testing should allow larger studies of the relationship between neurocognitive functioning, PHOX2B genotype/mutation, and disease severity and management.
authors: Department of Child and Adolescent Psychiatry, Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60614, USA.
authors: Frank A
authors: FA
authors: Zelko
authors: Michael N
authors: MN
authors: Nelson
authors: Sue E
authors: SE
authors: Leurgans
authors: Elizabeth M
authors: EM
authors: Berry-Kravis
authors: Debra E
authors: DE
authors: Weese-Mayer
mesh_terms: D000015:Abnormalities, Multiple / Q000453:epidemiology / Q000235:genetics; D000293:Adolescent; D000328:Adult; D001342:Autonomic Nervous System Diseases / Q000151:congenital / Q000453:epidemiology; D002641:Chicago / Q000453:epidemiology; D002648:Child; D002657:Child Development; D003071:Cognition; D003072:Cognition Disorders / Q000150:complications* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007040:Hypoventilation / Q000151:congenital* / Q000453:epidemiology* / Q000235:genetics; D007361:Intelligence Tests / Q000706:statistics & numerical data; D008297:Male; D008570:Memory, Short-Term; D009483:Neuropsychological Tests / Q000706:statistics & numerical data*; D011594:Psychometrics / Q000379:methods / Q000706:statistics & numerical data; D012307:Risk Factors; D012720:Severity of Illness Index; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult
chemical_list: D018398:Homeodomain Proteins; C109220:NBPhox protein; D014157:Transcription Factors