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Vagal and sympathetic heart rate and blood pressure control in adult onset PHOX2B mutation–confirmed congenital central hypoventilation syndrome

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Abstract

Background

Children with Congenital Central Hypoventilation Syndrome (CCHS) typically present as newborns with alveolar hypoventilation. With the advent of genetic testing, parents of affected children and other unrelated adults, all heterozygous for the disease-defining PHOX2B polyalanine expansion mutation with the 20/25 genotype, are being identified in adulthood. Though children with PHOX2B mutation-confirmed CCHS demonstrate ANS dysregulation, including altered heart rate and blood pressure control, it is unknown if adults with CCHS have similarly affected autonomic function in blood pressure control.

Methods and Results

An autonomic profile of blood pressure control has been studied with recording of muscle sympathetic activity and spectral analysis of heart rate and blood pressure variability of one adult patient with alveolar hypoventilation and the 20/25 PHOX2B genotype. All parameters of heart rate variability were reduced. Cardiac baroreflex sensitivity was decreased. Sympathetic responses to Valsalva maneuver, hypoxemia, isometric exercise and cold pressor were blunted.

Conclusion

In summary, we found a reduced cardiac baroreflex and a blunted sympathetic mediated response in the individual with adult-onset CCHS, possibly due to dysfunction in the afferent pathway. Our results confirm that PHOX2B affects the development of the autonomic nervous system, possibly causing absence of normal maturation of carotid body and visceral sensory ganglia and leading to autonomic dysfunction in adult-onset CCHS.

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Acknowledgements

This work was supported in part by National Institutes of Health grants M01 RR00095, 1PO1 HL56693, R01 HL71784 and R41 AG19576-01A1. We thank Peter Howard, Sachin Y Paranjape, Bonnie Black, Ginnie Farley, Suzanne Lonce and staff of the Vanderbilt University GCRC for their support. We appreciate the help of Madaline Corridan & Hannah Scott from Mary’s Hospital. We thank Dr. Thomas Hazinski for his kind referral of the patient.

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Authors and Affiliations

  1. Dept. of Medicine, Division of Clinical Pharmacology, Autonomic Dysfunction Center Vanderbilt University School of Medicine, Nashville, TN, USA

    André Diedrich MD, PhD, Kyoko Sato MD, PhD & David Robertson MD

  2. Dept. of Neurology, Vanderbilt University School of Medicine, Nashville, TN, USA

    Beth A. Malow MD, MS & David Robertson MD

  3. Vanderbilt Sleep Disorders Center, Vanderbilt University School of Medicine, Nashville, TN, USA

    Beth A. Malow MD, MS

  4. Adelaide Institute for Sleep Health, Repatriation General Hospital, Daw Park, SA, Australia

    Nick A. Antic MD & R. Doug McEvoy MD

  5. Autonomic Unit, National Hospital for Neurology & Neurosurgery, London, UK

    Christopher J. Mathias MD, MBBS, LRCP&S, DPhil, DSc, FRCP, FMedSci

  6. Neurovascular Medicine Unit, Faculty of Medicine, Imperial College London at St. Mary’s Hospital, London, UK

    Christopher J. Mathias MD, MBBS, LRCP&S, DPhil, DSc, FRCP, FMedSci

  7. Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, TN, USA

    David Robertson MD

  8. Dept. of Pediatrics, Rush University Medical Center, Chicago, IL, USA

    Elizabeth M. Berry-Kravis MD, PhD & Debra E. Weese-Mayer MD

  9. Dept. of Neurology and Biochemistry, Rush University Medical Center, Chicago, IL, USA

    Elizabeth M. Berry-Kravis MD, PhD

Authors
  1. André Diedrich MD, PhD
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  2. Beth A. Malow MD, MS
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  3. Nick A. Antic MD
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  4. Kyoko Sato MD, PhD
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  5. R. Doug McEvoy MD
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  6. Christopher J. Mathias MD, MBBS, LRCP&S, DPhil, DSc, FRCP, FMedSci
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  7. David Robertson MD
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  8. Elizabeth M. Berry-Kravis MD, PhD
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  9. Debra E. Weese-Mayer MD
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Correspondence to André Diedrich MD, PhD.

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Diedrich, A., Malow, B.A., Antic, N.A. et al. Vagal and sympathetic heart rate and blood pressure control in adult onset PHOX2B mutation–confirmed congenital central hypoventilation syndrome. Clin Auton Res 17, 177–185 (2007). https://doi.org/10.1007/s10286-007-0421-4

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  • DOI: https://doi.org/10.1007/s10286-007-0421-4

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