title: Congenital Central Hypoventilation Syndrome: Neurocognition Already Reduced in Preschool-Aged Children.
abstract: BACKGROUND
  Congenital Central Hypoventilation Syndrome (CCHS) is a rare neurocristopathy characterized by severe hypoventilation and autonomic dysregulation, with typical presentation in the neonatal period, and deficient cognitive skills in school-aged patients. We hypothesized that younger (preschool) children with CCHS would also show neurocognitive delay and that CCHS-related physiologic factors would impact neurocognitive test results.
  
  
  METHODS
  We studied developmental (Bayley) test results collected during routine clinical care in 31 children (mean age 25.0 ± 8.5 months; range, 6-40 months) with PHOX2B mutation-confirmed CCHS by comparing them with the normative reference mean from the Bayley standardization sample; we also examined associations between Bayley scores and CCHS disease-related factors.
  
  
  RESULTS
  Preschool patients with CCHS fell significantly below the normative mean of 100 on Bayley indices of mental (mean, 83.35 ± 24.75) and motor (mean, 73.33 ± 20.48) development (P < .001 for both). Significantly lower Bayley mental and motor scores were associated with severe breath-holding spells, prolonged sinus pauses, and need for 24 h/d artificial ventilation. Lower Bayley motor scores were also associated with seizures. Bayley scores differed among children with the three most common polyalanine repeat expansion mutation genotypes (mental, P = .001; motor, P = .006), being essentially normal in children with the 20/25 genotype but significantly lower in the other genotype groups (P < .05).
  
  
  CONCLUSIONS
  These results confirm neurodevelopmental impairment of CCHS preschoolers, with severity related to physiologic compromise and PHOX2B genotype. These findings suggest that adverse effects begin early in the disease process, supporting the need for neurodevelopmental monitoring and intervention from early infancy.
authors.affiliation: Center for Autonomic Medicine in Pediatrics, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago and The Stanley Manne Children's Research Institute, Chicago, IL.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Charnay
authors.affiliation: Department of Child and Adolescent Psychiatry, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Northwestern University Feinberg School of Medicine, Chicago, IL. Electronic address: JAntisdel@luriechildrens.com.
authors.forename: Jeanne E
authors.initials: JE
authors.lastname: Antisdel-Lomaglio
authors.affiliation: Department of Child and Adolescent Psychiatry, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Northwestern University Feinberg School of Medicine, Chicago, IL.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Zelko
authors.affiliation: Center for Autonomic Medicine in Pediatrics, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago and The Stanley Manne Children's Research Institute, Chicago, IL.
authors.forename: Casey M
authors.initials: CM
authors.lastname: Rand
authors.affiliation: Center for Autonomic Medicine in Pediatrics, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago and The Stanley Manne Children's Research Institute, Chicago, IL.
authors.forename: Michele
authors.initials: M
authors.lastname: Le
authors.affiliation: Center for Autonomic Medicine in Pediatrics, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago and The Stanley Manne Children's Research Institute, Chicago, IL.
authors.forename: Samantha C
authors.initials: SC
authors.lastname: Gordon
authors.affiliation: Center for Autonomic Medicine in Pediatrics, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago and The Stanley Manne Children's Research Institute, Chicago, IL.
authors.forename: Sally F
authors.initials: SF
authors.lastname: Vitez
authors.affiliation: Center for Autonomic Medicine in Pediatrics, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago and The Stanley Manne Children's Research Institute, Chicago, IL.
authors.forename: Jennifer W
authors.initials: JW
authors.lastname: Tse
authors.affiliation: Center for Autonomic Medicine in Pediatrics, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago and The Stanley Manne Children's Research Institute, Chicago, IL.
authors.forename: Cindy D
authors.initials: CD
authors.lastname: Brogadir
authors.affiliation: Departments of Pediatrics and Behavioral Sciences, Rush University Medical Center, Chicago, IL.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Nelson
authors.affiliation: Departments of Pediatrics, Neurological Sciences and Biochemistry, Rush University Medical Center, Chicago, IL.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Berry-Kravis
authors.affiliation: Center for Autonomic Medicine in Pediatrics, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago and The Stanley Manne Children's Research Institute, Chicago, IL; Northwestern University Feinberg School of Medicine, Chicago, IL.
authors.forename: Debra E
authors.initials: DE
authors.lastname: Weese-Mayer
mesh_terms: D001342:Autonomic Nervous System Diseases / Q000503:physiopathology*; D062485:Breath Holding; D002675:Child, Preschool; D015331:Cohort Studies; D042622:DNA Repeat Expansion; D002658:Developmental Disabilities / Q000503:physiopathology* / Q000523:psychology; D005260:Female; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007040:Hypoventilation / Q000151:congenital* / Q000235:genetics / Q000503:physiopathology / Q000523:psychology / Q000628:therapy; D007223:Infant; D008297:Male; D009048:Motor Skills / Q000502:physiology; D009154:Mutation; D009483:Neuropsychological Tests; D010455:Peptides / Q000235:genetics; D010641:Phenotype; D012121:Respiration, Artificial; D012189:Retrospective Studies; D012640:Seizures / Q000503:physiopathology*; D054138:Sinus Arrest, Cardiac / Q000503:physiopathology*; D020182:Sleep Apnea, Central / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology / Q000628:therapy; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; C109220:NBPhox protein; D010455:Peptides; D014157:Transcription Factors; C019529:polyalanine
keywords: cognitive function; genetics; hypoventilation