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Life-threatening cardiac arrhythmias in congenital central hypoventilation syndrome

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A Correction to this article was published on 11 February 2020

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Abstract

Congenital central hypoventilation syndrome (CCHS) patients are at risk for life-threatening cardiac arrhythmias, and presentation is dependent on their PHOX2B gene mutation. We describe the presentation of life-threatening arrhythmias in our cohort of CCHS patients. We reviewed the records of 72 CCHS patients seen at CHLA from 2004 to 2018. Data collected included demographics, PHOX2B genotype, ventilatory support, clinical symptoms, ambulatory cardiac monitoring results, and presence of cardiac pacemaker. Sixteen of 72 patients had evidence of potential life-threatening cardiac arrhythmias. PHOX2B genotypes were 20/25 polyalanine repeat expansion mutation (PARM), 20/26 PARM, 20/27 PARM, 20/32 PARM, and c.245C > T non-polyalanine repeat mutation. 11/16 patients were ventilated during sleep only. Symptoms included syncope, dizziness, chest pain, tingling in the left arm, and palpitations. 15/16 patients had recorded ambulatory cardiac monitoring. 5/16 patients were symptomatic without significant sinus pauses. 12/16 patients had implantation of cardiac pacemakers. 9/12 had significant sinus pauses on ambulatory monitoring, and 7/12 patients were symptomatic.

Conclusion: CCHS patients have potential life-threatening arrhythmias requiring cardiac pacemaker implantation. Many of these patients are symptomatic with significant sinus pauses on ambulatory monitoring. However, some symptomatic patients with no significant pauses on ambulatory monitoring may still require cardiac pacemaker implantation.

What is Known:

• CCHS patients are at risk for life-threatening sinus pauses and require cardiac pacemaker implantation.

What is New:

• CCHS patients regardless of PHOX2B genotype are at risk for significant sinus pauses. Many CCHS patients with significant sinus pause on ambulatory cardiac monitoring are symptomatic and most present with syncope. Some symptomatic patients do not have significant sinus pauses but may still require cardiac pacemaker implantation.

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Change history

  • 11 February 2020

    The publisher regrets that in the original published version of this article, one of the author���s name was incorrectly presented as ���Yaniv Bar Cohen���. The correct presentation should have been ���Yaniv Bar-Cohen��� and is now presented correctly in this article.

Abbreviations

CCHS:

Congenital central hypoventilation syndrome

DP:

Diaphragm pacing

NIPPV:

Noninvasive positive pressure ventilation

NPARM:

Non-polyalanine repeat mutation

PARM:

Polyalanine repeat expansion mutation

PPV:

Positive pressure ventilation

References

  1. Weese-Mayer DE, Berry-Kravis EM, Ceccherini I, Keens TG, Loghmanee DA, Trang H (2010) An official ATS clinical policy statement: congenital central hypoventilation syndrome: genetic basis, diagnosis, and management. Am J Respir Crit Care Med 181(6):626–644. https://doi.org/10.1164/rccm.200807-1069ST

    Article  CAS  PubMed  Google Scholar 

  2. Vanderlaan M, Holbrook CR, Wang M, Tuell A, Gozal D (2004) Epidemiologic survey of 196 patients with congenital central hypoventilation syndrome. Pediatr Pulmonol 37(3):217–229. https://doi.org/10.1002/ppul.10438

    Article  PubMed  Google Scholar 

  3. Silvestri JM, Hanna BD, Volgman AS, Jones PJ, Barnes SD, Weese-Mayer DE (2000) Cardiac rhythm disturbances among children with idiopathic congenital central hypoventilation syndrome. Pediatr Pulmonol 29(5):351–358 http://www.ncbi.nlm.nih.gov/pubmed/10790246. Accessed 4 Feb 2016

    Article  CAS  Google Scholar 

  4. Gronli JO, Santucci BA, Leurgans SE, Berry-Kravis EM, Weese-Mayer DE (2008) Congenital central hypoventilation syndrome: PHOX2B genotype determines risk for sudden death. Pediatr Pulmonol 43(1):77–86. https://doi.org/10.1002/ppul.20744

    Article  PubMed  Google Scholar 

  5. Mitacchione G, Bontempi L, Curnis A (2019) Clinical approach to cardiac pauses in congenital central hypoventilation syndrome. Pediatr Pulmonol 54(2):E4–E6. https://doi.org/10.1002/ppul.24189

    Article  PubMed  Google Scholar 

  6. Macey PM, Valderama C, Kim AH, Woo MA, Gozal D, Keens TG, Harper RM (2004) Temporal trends of cardiac and respiratory responses to ventilatory challenges in congenital central hypoventilation syndrome. Pediatr Res 55(6):953–959. https://doi.org/10.1203/01.PDR.0000125262.82405.3C

    Article  PubMed  Google Scholar 

  7. Diedrich A, Malow BA, Antic NA, Sato K, McEvoy RD, Mathias CJ, Roberston D, Berry-Kravis EM, Weese-Mayer DE (2007) Vagal and sympathetic heart rate and blood pressure control in adult onset PHOX2B mutation-confirmed congenital central hypoventilation syndrome. Clin Auton Res 17(3):177–185. https://doi.org/10.1007/s10286-007-0421-4

    Article  PubMed  Google Scholar 

  8. Trang H, Girard A, Laude D, Elghozi J-L (2005) Short-term blood pressure and heart rate variability in congenital central hypoventilation syndrome (Ondine’s curse). Clin Sci (Lond) 108(3):225–230. https://doi.org/10.1042/CS20040282

    Article  Google Scholar 

  9. Woo MS, Woo MA, Gozal D, Jansen MT, Keens TG, Harper RM (1992) Heart rate variability in congenital central hypoventilation syndrome. Pediatr Res 31(3):291–296. https://doi.org/10.1203/00006450-199203000-00020

    Article  CAS  PubMed  Google Scholar 

  10. Trang H, Boureghda S, Denjoy I, Alia M, Kabaker M (2003) 24-hour BP in children with congenital central hypoventilation syndrome. Chest. 124(4):1393–1399

    Article  Google Scholar 

  11. Kolb C, Eicken A, Zrenner B, Schmitt C (2006) Cardiac pacing in a patient with diaphragm pacing for congenital central hypoventilation syndrome (Ondine’s curse). J Cardiovasc Electrophysiol 17(7):789–791. https://doi.org/10.1111/j.1540-8167.2006.00405.x

    Article  PubMed  Google Scholar 

  12. Antic NA, Malow BA, Lange N, McEvoy RD, Olson AL, Turkington P, Windisch W, Samuels M, Stevens CA, Berry-Kravis EM, Weese-Mayer DE (2006) PHOX2B mutation–confirmed congenital central hypoventilation syndrome presentation in adulthood. Am J Respir Crit Care Med 174(8):923–927. https://doi.org/10.1164/rccm.200605-607CR

    Article  CAS  PubMed  Google Scholar 

  13. Kasi AS, Jurgensen TJ, Yen S, Kun SS, Keens TG, Perez IA (2017) Three-generation family with congenital central hypoventilation syndrome and novel PHOX2B gene non-polyalanine repeat mutation. J Clin Sleep Med 13(07):925–927. https://doi.org/10.5664/jcsm.6670

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Children’s Hospital Los Angeles, Los Angeles, CA, USA

    Eric Laifman, Thomas G. Keens, Yaniv Bar-Cohen & Iris A. Perez

  2. Keck School of Medicine of USC, Los Angeles, CA, USA

    Thomas G. Keens, Yaniv Bar-Cohen & Iris A. Perez

Authors
  1. Eric Laifman
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  2. Thomas G. Keens
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  3. Yaniv Bar-Cohen
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  4. Iris A. Perez
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Contributions

EL: Study Design, Data collection, Analysis, Manuscript

TK: Analysis, Manuscript

YBC: Analysis, Manuscript

IP: Study Design, Data collection, Analysis, Manuscript

Corresponding author

Correspondence to Iris A. Perez.

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The authors declare that they have no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Communicated by Peter de Winter

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The original version of this article was revised: One of the author’s name was incorrectly presented as “Yaniv Bar Cohen”. The correct presentation should have been “Yaniv Bar-Cohen” and is now presented correctly in this article.

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Laifman, E., Keens, T.G., Bar-Cohen, Y. et al. Life-threatening cardiac arrhythmias in congenital central hypoventilation syndrome. Eur J Pediatr 179, 821–825 (2020). https://doi.org/10.1007/s00431-019-03568-5

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  • DOI: https://doi.org/10.1007/s00431-019-03568-5

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