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Expanding the phenotype of congenital central hypoventilation syndrome impacts management decisions.
Am J Med Genet A. 2018 06; 176(6):1398-1404.AJ

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.

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Authors+Show Affiliations

Byers HM
Division of Medical Genetics, Department of Pediatrics, Stanford University, Palo Alto, California.
Chen M
Department of Pediatrics, University of Washington, Seattle, Washington. Division of Pulmonary Medicine, Seattle Children's Hospital, Seattle, Washington.
Gelfand AS
University of Texas Southwestern Medical School, Dallas, Texas.
Ong B
Division of Pediatric Pulmonology, Tripler Army Medical Center, Honolulu, Hawaii.
Jendras M
Children's Health, Dallas, Texas.
Glass IA
Department of Pediatrics, University of Washington, Seattle, Washington. Division of Medical Genetics, Seattle Children's Hospital, Seattle, Washington.

MeSH

AdultFemaleHomeodomain ProteinsHumansHypoventilationInfantInfant, NewbornMaleMutationPhenotypeSleep Apnea, CentralTranscription Factors

Pub Type(s)

Case Reports
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

29696799

Citation

Byers, Heather M., et al. "Expanding the Phenotype of Congenital Central Hypoventilation Syndrome Impacts Management Decisions." American Journal of Medical Genetics. Part A, vol. 176, no. 6, 2018, pp. 1398-1404.
Byers HM, Chen M, Gelfand AS, et al. Expanding the phenotype of congenital central hypoventilation syndrome impacts management decisions. Am J Med Genet A. 2018;176(6):1398-1404.
Byers, H. M., Chen, M., Gelfand, A. S., Ong, B., Jendras, M., & Glass, I. A. (2018). Expanding the phenotype of congenital central hypoventilation syndrome impacts management decisions. American Journal of Medical Genetics. Part A, 176(6), 1398-1404. https://doi.org/10.1002/ajmg.a.38726
Byers HM, et al. Expanding the Phenotype of Congenital Central Hypoventilation Syndrome Impacts Management Decisions. Am J Med Genet A. 2018;176(6):1398-1404. PubMed PMID: 29696799.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expanding the phenotype of congenital central hypoventilation syndrome impacts management decisions. AU - Byers,Heather M, AU - Chen,Maida, AU - Gelfand,Andrew S, AU - Ong,Bruce, AU - Jendras,Marisa, AU - Glass,Ian A, Y1 - 2018/04/25/ PY - 2017/06/21/received PY - 2018/04/01/revised PY - 2018/04/04/accepted PY - 2018/4/27/pubmed PY - 2019/5/22/medline PY - 2018/4/27/entrez KW - CCHS KW - PHOX2B KW - central congenital hypoventilation syndrome KW - genetic KW - respiratory SP - 1398 EP - 1404 JF - American journal of medical genetics. Part A JO - Am J Med Genet A VL - 176 IS - 6 N2 - 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. SN - 1552-4833 UR - https://www.unboundmedicine.com/medline/citation/29696799/Expanding_the_phenotype_of_congenital_central_hypoventilation_syndrome_impacts_management_decisions_ DB - PRIME DP - Unbound Medicine ER -