title: Later-onset congenital central hypoventilation syndrome due to a heterozygous 24-polyalanine repeat expansion mutation in the PHOX2B gene.
abstract: OBJECTIVE
  to describe a family with later onset congenital central hypoventilation syndrome (LO-CCHS) and heterozygosity for a 24-polyalanine repeat expansion mutation in the PHOX2B gene, rendered phenotypically apparent with exposure to anesthetics.
  
  
  METHODS
  An otherwise healthy 2.75-year-old boy presented with alveolar hypoventilation after adenoidectomy and tonsillectomy for obstructive sleep apnea, requiring invasive ventilatory support during sleep. He had a heterozygous 24-polyalanine repeat expansion in the PHOX2B gene (20/24 genotype), a genotype that has not been previously described in association with CCHS or LO-CCHS symptoms. Clinical findings in members of the family with the same 20/24 genotype ranged from asymptomatic to prolonged sedation after benzodiazepines.
  
  
  CONCLUSIONS
  CCHS should be suspected in individuals presenting with unexplained hypoventilation and/or seizures after anesthetics or sedatives. This is the first report of LO-CCHS in a kindred with the PHOX2B 20/24 genotype. The incomplete penetrance observed in this family suggests a gene-environment interaction.
authors.affiliation: Human Genetics Center, Facultad de Medicina, Clinica Alemana-Universidad del Desarrollo, Santiago, Chile.
authors.forename: Gabriela M
authors.initials: GM
authors.lastname: Repetto
authors.forename: Raul J
authors.initials: RJ
authors.lastname: Corrales
authors.forename: Selim G
authors.initials: SG
authors.lastname: Abara
authors.forename: Lili
authors.initials: L
authors.lastname: Zhou
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Berry-Kravis
authors.forename: Casey M
authors.initials: CM
authors.lastname: Rand
authors.forename: Debra E
authors.initials: DE
authors.lastname: Weese-Mayer
mesh_terms: D017668:Age of Onset; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007040:Hypoventilation / Q000235:genetics*; D008297:Male; D010455:Peptides / Q000235:genetics; D020182:Sleep Apnea, Central / Q000151:congenital / Q000601:surgery; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C109220:NBPhox protein; D010455:Peptides; D014157:Transcription Factors; C019529:polyalanine