» Articles » PMID: 29696799

Expanding the Phenotype of Congenital Central Hypoventilation Syndrome Impacts Management Decisions

Overview
Specialty Genetics
Date 2018 Apr 27
PMID 29696799
Citations 6
Authors
Affiliations
Soon will be listed here.
Abstract

Congenital central hypoventilation syndrome (CCHS) is a neurocristopathy caused by pathogenic heterozygous variants in the gene paired-like homeobox 2b (PHOX2B). It is characterized by severe infantile alveolar hypoventilation. Individuals may also have diffuse autonomic nervous system dysfunction, Hirschsprung disease and neural crest tumors. We report three individuals with CCHS due to an 8-base pair duplication in PHOX2B; c.691_698dupGGCCCGGG (p.Gly234Alafs*78) with a predominant enteral and neural crest phenotype and a relatively mild respiratory phenotype. The attenuated respiratory phenotype reported here and elsewhere suggests an emergent genotype:phenotype correlation which challenges the current paradigm of invoking mechanical ventilation for all infants diagnosed with CCHS. Best treatment requires careful clinical judgment and ideally the assistance of a care team with expertise in CCHS.

Citing Articles

Images: Atypical presentation of congenital central hypoventilation syndrome in an infant with central and obstructive sleep apnea.

Fain M, Raghunandan S, Pencheva B, Leu R, Kasi A J Clin Sleep Med. 2023; 20(3):478-481.

PMID: 37861394 PMC: 11019219. DOI: 10.5664/jcsm.10884.


Congenital central hypoventilation syndrome in Chinese population: Analysis of three new cases and review of the literature.

Wang Y, Wang L, Chen X, Liu S, Han W, Yu X Mol Genet Genomic Med. 2023; 11(12):e2267.

PMID: 37712713 PMC: 10724499. DOI: 10.1002/mgg3.2267.


Case Report: A novel p.Ala248_Ala266dup variant causing congenital central hypoventilation syndrome.

Artamonova I, Zlotina A, Ismagilova O, Levko T, Kolbina N, Bryzzhin A Front Pediatr. 2023; 10:1070303.

PMID: 36874254 PMC: 9975566. DOI: 10.3389/fped.2022.1070303.


Congenital central hypoventilation syndrome in neonates: report of fourteen new cases and a review of the literature.

Mei M, Yang L, Lu Y, Wang L, Cheng G, Cao Y Transl Pediatr. 2021; 10(4):733-745.

PMID: 34012823 PMC: 8107878. DOI: 10.21037/tp-20-303.


Recurrent apnea in an infant: Lessons for the clinician.

Karmani S, Pandey A, Shridhar G, Simalti A, Goswami J Med J Armed Forces India. 2020; 76(4):466-468.

PMID: 33162659 PMC: 7606096. DOI: 10.1016/j.mjafi.2018.07.014.


References
1.
Kasi A, Jurgensen T, Yen S, Kun S, Keens T, Perez I . Three-Generation Family With Congenital Central Hypoventilation Syndrome and Novel Gene Non-Polyalanine Repeat Mutation. J Clin Sleep Med. 2017; 13(7):925-927. PMC: 5482585. DOI: 10.5664/jcsm.6670. View

2.
Berry-Kravis E, Zhou L, Rand C, Weese-Mayer D . Congenital central hypoventilation syndrome: PHOX2B mutations and phenotype. Am J Respir Crit Care Med. 2006; 174(10):1139-44. DOI: 10.1164/rccm.200602-305OC. View

3.
Di Lascio S, Bachetti T, Saba E, Ceccherini I, Benfante R, Fornasari D . Transcriptional dysregulation and impairment of PHOX2B auto-regulatory mechanism induced by polyalanine expansion mutations associated with congenital central hypoventilation syndrome. Neurobiol Dis. 2012; 50:187-200. DOI: 10.1016/j.nbd.2012.10.019. View

4.
Raabe E, Laudenslager M, Winter C, Wasserman N, Cole K, LaQuaglia M . Prevalence and functional consequence of PHOX2B mutations in neuroblastoma. Oncogene. 2007; 27(4):469-76. DOI: 10.1038/sj.onc.1210659. View

5.
Williams P, Wegner E, Ziegler D . Outcomes in multifocal neuroblastoma as part of the neurocristopathy syndrome. Pediatrics. 2014; 134(2):e611-6. DOI: 10.1542/peds.2013-3340. View