Developmental alterations of the respiratory human retrotrapezoid nucleus in sudden unexplained fetal and infant death

Auton Neurosci. 2012 Sep 25;170(1-2):12-9. doi: 10.1016/j.autneu.2012.06.005. Epub 2012 Jul 15.


The study aims were twofold: 1) identify the localization and the cytoarchitecture of the retrotrapezoid nucleus (RTN) in the human fetus and infant and 2) ascertain if the RTN, given its essential role in animal studies for the maintenance of breathing and chemoreception, showed abnormalities in victims of sudden perinatal and infant death (sudden intrauterine unexplained death/SIUD - and sudden infant death syndrome/SIDS). We examined SIDS and SIUD cases and Controls (n=58) from 34 gestational weeks to 8 months of postnatal age by complete autopsy, in-depth autonomic nervous system histological examination, and immunohistochemical analysis of the PHOX2B gene, a transcriptional factor involved in Congenital Central Hypoventilation Syndrome that has been defined as a marker of rat RTN neurons. We identified a group of PHOX2B-immunopositive neurons within the caudal pons, contiguous to the facial/parafacial complex, in 90% of Controls, likely the homologous human RTN (hRTN). We observed structural and/or PHOX2B-expression abnormalities of the hRTN in 71% of SIUD/SIDS cases vs 10% of Controls (p<0.05). In conclusion we suggest that developmental abnormalities of the hRTN may seriously compromise chemoreception control, playing a critical role in the pathogenesis of both SIUD and SIDS.

MeSH terms

  • Autopsy
  • Brain Stem / cytology
  • Brain Stem / growth & development
  • Brain Stem / metabolism
  • Brain Stem / pathology*
  • Case-Control Studies
  • Cell Count / statistics & numerical data
  • Cerebellum / cytology
  • Cerebellum / growth & development
  • Cerebellum / pathology
  • Female
  • Fetal Death / pathology*
  • Fluorescent Antibody Technique / methods
  • Homeodomain Proteins / metabolism
  • Humans
  • Hypoventilation / congenital
  • Hypoventilation / pathology
  • Infant
  • Male
  • Neurons / cytology
  • Neurons / pathology
  • Sleep Apnea, Central / pathology
  • Sudden Infant Death / pathology*
  • Transcription Factors / metabolism
  • Tyrosine 3-Monooxygenase / metabolism


  • Homeodomain Proteins
  • NBPhox protein
  • Transcription Factors
  • Tyrosine 3-Monooxygenase

Supplementary concepts

  • Congenital central hypoventilation syndrome