title: Pupillometry in congenital central hypoventilation syndrome (CCHS): quantitative evidence of autonomic nervous system dysregulation.
abstract: BACKGROUND
  Congenital central hypoventilation syndrome (CCHS) is characterized by alveolar hypoventilation, autonomic nervous system (ANS) dysregulation (ANSD), and mutations in the paired-like homeobox 2B (PHOX2B) gene. ANSD in CCHS affects multiple systems and includes ophthalmologic abnormalities. We hypothesized that quantitative pupil measures, obtained using pupillometry, would vary between cases with CCHS and controls and within those with CCHS by PHOX2B genotype.
  
  
  RESULTS
  Measures known to be illustrative of sympathetic and parasympathetic response (prestimulus, maximum pupil diameter, percentage of pupil constriction after light stimulus, and average constriction and dilation velocities) were significantly reduced in those with CCHS as compared with controls (all P < 0.05).
  
  
  CONCLUSIONS
  These reductions are indicative of both sympathetic and parasympathetic deficits in CCHS, which is in keeping with the role of PHOX2B in ANS development. An inverse linear relationship was apparent in pupil diameter and velocity measurements among the cases with CCHS with the most common heterozygous PHOX2B polyalanine expansion repeat mutations, suggesting a graded phenotype/genotype dose response based on polyalanine repeat length. These results confirm our central hypotheses while offering the first objective measures of pupillary dysfunction and ophthalmologic-specific ANSD in CCHS.
  
  
  METHODS
  A total of 316 monocular measurements were taken under dark-adapted conditions with a fixed light stimulus from 22 PHOX2B mutation-confirmed cases with CCHS and 68 healthy controls.
authors.affiliation: Department of Pediatrics, Center for Autonomic Medicine in Pediatrics, Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. PPatwari@ChildrensMemorial.org
authors.forename: Pallavi P
authors.initials: PP
authors.lastname: Patwari
authors.forename: Tracey M
authors.initials: TM
authors.lastname: Stewart
authors.forename: Casey M
authors.initials: CM
authors.lastname: Rand
authors.forename: Michael S
authors.initials: MS
authors.lastname: Carroll
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Kuntz
authors.forename: Anna S
authors.initials: AS
authors.lastname: Kenny
authors.forename: Cindy D
authors.initials: CD
authors.lastname: Brogadir
authors.forename: Debra E
authors.initials: DE
authors.lastname: Weese-Mayer
mesh_terms: D000293:Adolescent; D001342:Autonomic Nervous System Diseases / Q000175:diagnosis / Q000503:physiopathology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007040:Hypoventilation / Q000151:congenital* / Q000235:genetics / Q000503:physiopathology; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics; D009885:Ophthalmology / Q000379:methods*; D010275:Parasympathetic Nervous System / Q000503:physiopathology; D011680:Pupil / Q000502:physiology*; D012025:Reflex, Pupillary / Q000502:physiology*; D020182:Sleep Apnea, Central / Q000235:genetics / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult
chemical_list: D018398:Homeodomain Proteins; C109220:NBPhox protein; D014157:Transcription Factors