Adult-onset congenital central hypoventilation syndrome due to PHOX2B mutation

Acta Neurol Belg. 2021 Feb;121(1):23-35. doi: 10.1007/s13760-020-01363-w. Epub 2020 Apr 25.

Abstract

Central hypoventilation in adult patients is a rare life-threatening condition characterised by the loss of automatic breathing, more pronounced during sleep. In most cases, it is secondary to a brainstem lesion or to a primary pulmonary, cardiac or neuromuscular disease. More rarely, it can be a manifestation of congenital central hypoventilation syndrome (CCHS). We here describe a 25-year-old woman with severe central hypoventilation triggered by analgesics. Genetic analysis confirmed the diagnosis of adult-onset CCHS caused by a heterozygous de novo poly-alanine repeat expansion of the PHOX2B gene. She was treated with nocturnal non-invasive ventilation. We reviewed the literature and found 21 genetically confirmed adult-onset CCHS cases. Because of the risk of deleterious respiratory complications, adult-onset CCHS is an important differential diagnosis in patients with central hypoventilation.

Keywords: Autonomic; Central congenital hypoventilation syndrome; Hirschsprung disease; Neural crest tumours; PHOX2B; Polyalanine repeat expansion mutation.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Age of Onset
  • Female
  • Homeodomain Proteins / genetics*
  • Humans
  • Hypoventilation / congenital*
  • Hypoventilation / diagnostic imaging
  • Hypoventilation / genetics
  • Mutation / genetics*
  • Sleep Apnea, Central / diagnostic imaging*
  • Sleep Apnea, Central / genetics*
  • Transcription Factors / genetics*

Substances

  • Homeodomain Proteins
  • NBPhox protein
  • Transcription Factors

Supplementary concepts

  • Congenital central hypoventilation syndrome