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

  • Anna M. Lavezzi
    Correspondence
    Corresponding author at: Lino Rossi Research Center, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Via Commenda 19, 20122 Milan, Italy 20122. Tel.: +39 02 50320821.
    Affiliations
    “Lino Rossi” Research Center for the Study and Prevention of Unexpected Perinatal Death and SIDS, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan 20122, Italy
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  • Debra E. Weese-Mayer
    Affiliations
    Center for Autonomic Medicine in Pediatrics (CAMP), Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
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  • Margaret Y. Yu
    Affiliations
    Center for Autonomic Medicine in Pediatrics (CAMP), Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
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  • Lawrence J. Jennings
    Affiliations
    Molecular Diagnostics Laboratory, Department of Pathology, Ann & Robert H. Lurie Children's Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
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  • Melissa F. Corna
    Affiliations
    “Lino Rossi” Research Center for the Study and Prevention of Unexpected Perinatal Death and SIDS, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan 20122, Italy
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  • Valentina Casale
    Affiliations
    “Lino Rossi” Research Center for the Study and Prevention of Unexpected Perinatal Death and SIDS, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan 20122, Italy
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  • Roberta Oneda
    Affiliations
    “Lino Rossi” Research Center for the Study and Prevention of Unexpected Perinatal Death and SIDS, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan 20122, Italy
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  • Luigi Matturri
    Affiliations
    “Lino Rossi” Research Center for the Study and Prevention of Unexpected Perinatal Death and SIDS, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan 20122, Italy
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      Abstract

      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.

      Keywords

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