Later-onset congenital central hypoventilation syndrome due to a heterozygous 24-polyalanine repeat expansion mutation in the PHOX2B gene


Debra E. Weese-Mayer, M.D., Professor of
Pediatrics at Northwestern University Feinberg
School of Medicine, Center for Autonomic Medicine
in Pediatrics (CAMP), Children's Memorial Hospital,
2300 Children's Plaza, Mailbox #165,
Chicago, IL 60614, USA.
Tel: 773-880-8188 |
Fax: 773-880-8100 |


Aim: 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.

Case summary: 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.

Conclusion: 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.