Congenital central hypoventilation syndrome: An overview of etiopathogenesis, associated pathologies, clinical presentation, and management

Auton Neurosci. 2018 Mar:210:1-9. doi: 10.1016/j.autneu.2017.11.003. Epub 2017 Nov 13.

Abstract

Congenital central hypoventilation syndrome (CCHS), known colloquially as Ondine's curse, is a rare disorder characterized by impaired autonomic control of breathing during sleep from the loss of vagal input and diminished sensitivity of CO2 receptors in the medulla. CCHS correlates to the malformation of the neural crest located in the brainstem; this consequently affects the loss of sensitivity of CO2 chemoreceptors, bringing about hypoventilation during sleep. The primary cause of CCHS is the mutation of the paired-like homeobox PHO2XB gene, found in 90% of the patients. This mutation not only affects breathing but also drives neurological abnormalities such as autonomic and neurocognitive dysfunction. Though typically congenital, there have been late-onset (i.e., acquired) cases reported. It is vital for physicians and clinicians to be able to diagnose CCHS due to its similar presentation to other syndromes and disorders, which may cause it to be misdiagnosed and may account for its deleterious effects. CCHS can lead to a constellation of symptoms, and consideration of diseases that present concomitantly with CCHS affords us a better understanding of the etiology of this illness. Although a rare syndrome, we aim to review the current literature to emphasize the pathogenesis, etiology, clinical presentation, symptoms, diagnosis, and current treatment methods of CCHS for clinicians to better identify and understand this condition.

Keywords: Congenital central hypoventilation syndrome; Diaphragm pacing; Hirschsprung's disease; Ondine's curse; Positive-pressure ventilation; Progestin; Sudden infant death syndrome.

Publication types

  • Review

MeSH terms

  • Disease Management*
  • Homeodomain Proteins / genetics*
  • Humans
  • Hypoventilation / congenital*
  • Hypoventilation / etiology
  • Hypoventilation / genetics
  • Hypoventilation / pathology
  • Hypoventilation / therapy
  • Mutation / genetics*
  • Sleep Apnea, Central* / etiology
  • Sleep Apnea, Central* / genetics
  • Sleep Apnea, Central* / pathology
  • Sleep Apnea, Central* / therapy
  • Transcription Factors / genetics*

Substances

  • Homeodomain Proteins
  • NBPhox protein
  • Transcription Factors

Supplementary concepts

  • Congenital central hypoventilation syndrome