Expanding the phenotype of congenital central hypoventilation syndrome impacts management decisions

Heather M. Byers, Maida Chen, Andrew S. Gelfand, Bruce Ong, Marisa Jendras, Ian A. Glass

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Congenital central hypoventilation syndrome (CCHS) is a neurocristopathy caused by pathogenic heterozygous variants in the gene paired-like homeobox 2b (PHOX2B). It is characterized by severe infantile alveolar hypoventilation. Individuals may also have diffuse autonomic nervous system dysfunction, Hirschsprung disease and neural crest tumors. We report three individuals with CCHS due to an 8-base pair duplication in PHOX2B; c.691_698dupGGCCCGGG (p.Gly234Alafs*78) with a predominant enteral and neural crest phenotype and a relatively mild respiratory phenotype. The attenuated respiratory phenotype reported here and elsewhere suggests an emergent genotype:phenotype correlation which challenges the current paradigm of invoking mechanical ventilation for all infants diagnosed with CCHS. Best treatment requires careful clinical judgment and ideally the assistance of a care team with expertise in CCHS.

Original languageEnglish (US)
Pages (from-to)1398-1404
Number of pages7
JournalAmerican Journal of Medical Genetics, Part A
Issue number6
StatePublished - Jun 2018


  • CCHS
  • PHOX2B
  • central congenital hypoventilation syndrome
  • genetic
  • respiratory

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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