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Variable phenotypes in congenital central hypoventilation syndrome with PHOX2B nonpolyalanine repeat mutations.
J Clin Sleep Med. 2021 10 01; 17(10):2049-2055.JC

Abstract

STUDY OBJECTIVES

Congenital central hypoventilation syndrome (CCHS) is a rare disorder affecting the autonomic nervous system that is caused by variants in the paired-like homeobox 2B (PHOX2B) gene. About 10% of patients with CCHS have nonpolyalanine repeat mutations (NPARM) that are associated with severe phenotypes requiring continuous assisted ventilation, Hirschsprung's disease, and increased neural crest tumor risk. However, some patients with NPARM have milder phenotypes. Our objective was to describe the phenotypes in patients with CCHS PHOX2B NPARM.

METHODS

Retrospective case series of patients with CCHS PHOX2B NPARM was conducted at 2 children's hospitals to evaluate their phenotypes.

RESULTS

We identified 8 patients with CCHS PHOX2B NPARM aged 3-31 years. Seven patients were diagnosed in infancy and 1 patient at 2 years of age. All patients presented with respiratory depression in the first 2 months of life. Only 1 patient was identified with a severe phenotype requiring continuous assisted ventilation, Hirschsprung's disease, and a neural crest tumor, which was resected. Five patients required positive pressure ventilation via tracheostomy only during sleep and 2 patients required oxygen only during sleep. Four patients had Hirschsprung's disease and 1 patient had a cardiac pacemaker due to a bradyarrhythmia. None of the patients had echocardiographic abnormalities.

CONCLUSIONS

Patients with CCHS PHOX2B NPARM can have variable phenotypes, emphasizing the importance of implementing a plan of care that is individualized for each patient. The type of NPARM and their respective location on the PHOX2B gene may play a critical role in the severity of phenotypes displayed by each patient.

CITATION

Kasi AS, Li H, Jurgensen TJ, Guglani L, Keens TG, Perez IA. Variable phenotypes in congenital central hypoventilation syndrome with PHOX2B nonpolyalanine repeat mutations. J Clin Sleep Med. 2021;17(10):2049-2055.

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Authors+Show Affiliations

Kasi AS
Department of Pediatrics, Division of Pediatric Pulmonology, Emory University, Children's Healthcare of Atlanta, Atlanta, Georgia.
Li H
Department of Human Genetics, Emory University, Children's Healthcare of Atlanta, Atlanta, Georgia.
Jurgensen TJ
Department of Pediatrics, Division of Pediatric Pulmonology and Sleep Medicine, Children's Hospital Los Angeles, Los Angeles, California.
Guglani L
Department of Pediatrics, Division of Pediatric Pulmonology, Emory University, Children's Healthcare of Atlanta, Atlanta, Georgia.
Keens TG
Department of Pediatrics, Division of Pediatric Pulmonology and Sleep Medicine, Children's Hospital Los Angeles, Los Angeles, California. Keck School of Medicine of the University of Southern California, Los Angeles, California.
Perez IA
Department of Pediatrics, Division of Pediatric Pulmonology and Sleep Medicine, Children's Hospital Los Angeles, Los Angeles, California. Keck School of Medicine of the University of Southern California, Los Angeles, California.

MeSH

Homeodomain ProteinsHumansHypoventilationMutationPhenotypeRetrospective StudiesSleep Apnea, CentralTranscription Factors

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33983112

Citation

Kasi, Ajay S., et al. "Variable Phenotypes in Congenital Central Hypoventilation Syndrome With PHOX2B Nonpolyalanine Repeat Mutations." Journal of Clinical Sleep Medicine : JCSM : Official Publication of the American Academy of Sleep Medicine, vol. 17, no. 10, 2021, pp. 2049-2055.
Kasi AS, Li H, Jurgensen TJ, et al. Variable phenotypes in congenital central hypoventilation syndrome with PHOX2B nonpolyalanine repeat mutations. J Clin Sleep Med. 2021;17(10):2049-2055.
Kasi, A. S., Li, H., Jurgensen, T. J., Guglani, L., Keens, T. G., & Perez, I. A. (2021). Variable phenotypes in congenital central hypoventilation syndrome with PHOX2B nonpolyalanine repeat mutations. Journal of Clinical Sleep Medicine : JCSM : Official Publication of the American Academy of Sleep Medicine, 17(10), 2049-2055. https://doi.org/10.5664/jcsm.9370
Kasi AS, et al. Variable Phenotypes in Congenital Central Hypoventilation Syndrome With PHOX2B Nonpolyalanine Repeat Mutations. J Clin Sleep Med. 2021 10 1;17(10):2049-2055. PubMed PMID: 33983112.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Variable phenotypes in congenital central hypoventilation syndrome with PHOX2B nonpolyalanine repeat mutations. AU - Kasi,Ajay S, AU - Li,Hong, AU - Jurgensen,Taryn J, AU - Guglani,Lokesh, AU - Keens,Thomas G, AU - Perez,Iris A, PY - 2021/5/14/pubmed PY - 2021/12/15/medline PY - 2021/5/13/entrez KW - CCHS KW - NPARM KW - PHOX2B KW - congenital central hypoventilation syndrome SP - 2049 EP - 2055 JF - Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine JO - J Clin Sleep Med VL - 17 IS - 10 N2 - STUDY OBJECTIVES: Congenital central hypoventilation syndrome (CCHS) is a rare disorder affecting the autonomic nervous system that is caused by variants in the paired-like homeobox 2B (PHOX2B) gene. About 10% of patients with CCHS have nonpolyalanine repeat mutations (NPARM) that are associated with severe phenotypes requiring continuous assisted ventilation, Hirschsprung's disease, and increased neural crest tumor risk. However, some patients with NPARM have milder phenotypes. Our objective was to describe the phenotypes in patients with CCHS PHOX2B NPARM. METHODS: Retrospective case series of patients with CCHS PHOX2B NPARM was conducted at 2 children's hospitals to evaluate their phenotypes. RESULTS: We identified 8 patients with CCHS PHOX2B NPARM aged 3-31 years. Seven patients were diagnosed in infancy and 1 patient at 2 years of age. All patients presented with respiratory depression in the first 2 months of life. Only 1 patient was identified with a severe phenotype requiring continuous assisted ventilation, Hirschsprung's disease, and a neural crest tumor, which was resected. Five patients required positive pressure ventilation via tracheostomy only during sleep and 2 patients required oxygen only during sleep. Four patients had Hirschsprung's disease and 1 patient had a cardiac pacemaker due to a bradyarrhythmia. None of the patients had echocardiographic abnormalities. CONCLUSIONS: Patients with CCHS PHOX2B NPARM can have variable phenotypes, emphasizing the importance of implementing a plan of care that is individualized for each patient. The type of NPARM and their respective location on the PHOX2B gene may play a critical role in the severity of phenotypes displayed by each patient. CITATION: Kasi AS, Li H, Jurgensen TJ, Guglani L, Keens TG, Perez IA. Variable phenotypes in congenital central hypoventilation syndrome with PHOX2B nonpolyalanine repeat mutations. J Clin Sleep Med. 2021;17(10):2049-2055. SN - 1550-9397 UR - https://www.unboundmedicine.com/medline/citation/33983112/Variable_phenotypes_in_congenital_central_hypoventilation_syndrome_with_PHOX2B_nonpolyalanine_repeat_mutations_ DB - PRIME DP - Unbound Medicine ER -