Congenital central hypoventilation syndrome: Severe disease caused by co-occurrence of two PHOX2B variants inherited separately from asymptomatic family members

Yakov Sivan*, Amy Zhou, Lawrence J. Jennings, Elizabeth M. Berry-Kravis, Min Yu, Lili Zhou, Casey M. Rand, Debra E. Weese-Mayer

*Corresponding author for this work

Research output: Contribution to journalArticle


Congenital Central Hypoventilation Syndrome (CCHS) is a rare disease characterized by autonomic nervous system dysregulation. Central hypoventilation is the most prominent and clinically important presentation. CCHS is caused by mutations in paired-like homeobox 2b (PHOX2B) and is inherited in an autosomal dominant pattern. A co-occurrence of two asymptomatic PHOX2B variants with a classical CCHS presentation highlights the importance of clinical PHOX2B testing in parents and family members of all CCHS probands. Despite being an autosomal dominant disease, once a polyalanine repeat expansion mutation has been identified, sequencing of the other allele should also be considered.

Original languageEnglish (US)
Pages (from-to)503-506
Number of pages4
JournalAmerican Journal of Medical Genetics, Part A
Issue number3
StatePublished - Mar 2019



  • CCHS
  • autosomal dominant
  • autosomal recessive
  • non-polyalanine repeat mutation
  • polyalanine repeat expansion mutation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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