Later-onset congenital central hypoventilation syndrome due to a heterozygous 24-polyalanine repeat expansion mutation in the PHOX2B gene.
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.
Repetto
Gabriela M
GM
Human Genetics Center, Facultad de Medicina, Clinica Alemana-Universidad del Desarrollo, Santiago, Chile.
Corrales
Raul J
RJ
Abara
Selim G
SG
Zhou
Lili
L
Berry-Kravis
Elizabeth M
EM
Rand
Casey M
CM
Weese-Mayer
Debra E
DE
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*
D018398:Homeodomain Proteins; C109220:NBPhox protein; D010455:Peptides; D014157:Transcription Factors; C019529:polyalanine