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Congenital central hypoventilation syndrome in neonates: report of fourteen new cases and a review of the literature
BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare autosomal dominant disorder caused by pathogenic variants in paired-like homeobox 2B (PHOX2B) gene. Characteristics of neonatal-onset CCHS cases have not been well assessed. The aim of this study is to expand current knowledge...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107878/ https://www.ncbi.nlm.nih.gov/pubmed/34012823 http://dx.doi.org/10.21037/tp-20-303 |
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author | Mei, Mei Yang, Lin Lu, Yulan Wang, Laishuan Cheng, Guoqiang Cao, Yun Chen, Chao Qian, Liling Zhou, Wenhao |
author_facet | Mei, Mei Yang, Lin Lu, Yulan Wang, Laishuan Cheng, Guoqiang Cao, Yun Chen, Chao Qian, Liling Zhou, Wenhao |
author_sort | Mei, Mei |
collection | PubMed |
description | BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare autosomal dominant disorder caused by pathogenic variants in paired-like homeobox 2B (PHOX2B) gene. Characteristics of neonatal-onset CCHS cases have not been well assessed. The aim of this study is to expand current knowledge of clinical and genetic features of neonates with CCHS and provide data on the genotype-phenotype correlation. METHODS: We made a retrospective analysis of 14 neonates carrying PHOX2B pathogenic variants from 2014 to 2019 and we reviewed previously published neonatal-onset cases. Clinical and genetic data were analyzed. Moreover, genotype-phenotype correlation analysis was performed. RESULTS: We identified a total of 60 neonatal-onset CCHS cases (35 males and 25 females) including 14 novel cases from our local cohort. Nearly 20% (18.2%) of the patients were born prematurely. Nearly half (46.2%) of the patients had abnormal family history. Polyhydramnios was observed in 21.3% (10/47) of the patients. About 90% of the patients manifested symptoms of hypoventilation in the first week of life. Fourteen patients (23.3%) were classified as mild-CCHS and the rest were severe-CCHS. Gastrointestinal manifestations were observed in 71.7% of the patients. Approximately twofold more males than females were affected by Hirschprung disease (HSCR)/variant HSCR (75.8% vs. 35%, P=0.003). Neural crest tumor occurred in 9.1% (4/44) patients. Half patients had polyalanine repeat expansion mutations (PARMs) in PHOX2B (seven with 25 PARM, nine with 26 PARM, twelve with 27 PARM, one with 28 PARM and one with 31 PARM) and the other half patients had 23 distinct non-polyalanine repeat expansion mutations (NPARMs) with one novel pathogenic variant (c.684dup). The prevalence of HSCR and mild-CCHS among patients with NPARMs was significantly greater than that of the patients with PARMs. CONCLUSIONS: This report provides a large cohort of neonatal-onset CCHS cases. The results indicate that severe hypoventilation and HSCR are frequently observed in this group. NPARMs accounted for half of the cohort with some genotypes tend to be associated with mild phenotype. Molecular testing in neonates with suspicion of CCHS and genetic counseling for CCHS families are highly recommended. |
format | Online Article Text |
id | pubmed-8107878 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-81078782021-05-18 Congenital central hypoventilation syndrome in neonates: report of fourteen new cases and a review of the literature Mei, Mei Yang, Lin Lu, Yulan Wang, Laishuan Cheng, Guoqiang Cao, Yun Chen, Chao Qian, Liling Zhou, Wenhao Transl Pediatr Original Article BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare autosomal dominant disorder caused by pathogenic variants in paired-like homeobox 2B (PHOX2B) gene. Characteristics of neonatal-onset CCHS cases have not been well assessed. The aim of this study is to expand current knowledge of clinical and genetic features of neonates with CCHS and provide data on the genotype-phenotype correlation. METHODS: We made a retrospective analysis of 14 neonates carrying PHOX2B pathogenic variants from 2014 to 2019 and we reviewed previously published neonatal-onset cases. Clinical and genetic data were analyzed. Moreover, genotype-phenotype correlation analysis was performed. RESULTS: We identified a total of 60 neonatal-onset CCHS cases (35 males and 25 females) including 14 novel cases from our local cohort. Nearly 20% (18.2%) of the patients were born prematurely. Nearly half (46.2%) of the patients had abnormal family history. Polyhydramnios was observed in 21.3% (10/47) of the patients. About 90% of the patients manifested symptoms of hypoventilation in the first week of life. Fourteen patients (23.3%) were classified as mild-CCHS and the rest were severe-CCHS. Gastrointestinal manifestations were observed in 71.7% of the patients. Approximately twofold more males than females were affected by Hirschprung disease (HSCR)/variant HSCR (75.8% vs. 35%, P=0.003). Neural crest tumor occurred in 9.1% (4/44) patients. Half patients had polyalanine repeat expansion mutations (PARMs) in PHOX2B (seven with 25 PARM, nine with 26 PARM, twelve with 27 PARM, one with 28 PARM and one with 31 PARM) and the other half patients had 23 distinct non-polyalanine repeat expansion mutations (NPARMs) with one novel pathogenic variant (c.684dup). The prevalence of HSCR and mild-CCHS among patients with NPARMs was significantly greater than that of the patients with PARMs. CONCLUSIONS: This report provides a large cohort of neonatal-onset CCHS cases. The results indicate that severe hypoventilation and HSCR are frequently observed in this group. NPARMs accounted for half of the cohort with some genotypes tend to be associated with mild phenotype. Molecular testing in neonates with suspicion of CCHS and genetic counseling for CCHS families are highly recommended. AME Publishing Company 2021-04 /pmc/articles/PMC8107878/ /pubmed/34012823 http://dx.doi.org/10.21037/tp-20-303 Text en 2021 Translational Pediatrics. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Mei, Mei Yang, Lin Lu, Yulan Wang, Laishuan Cheng, Guoqiang Cao, Yun Chen, Chao Qian, Liling Zhou, Wenhao Congenital central hypoventilation syndrome in neonates: report of fourteen new cases and a review of the literature |
title | Congenital central hypoventilation syndrome in neonates: report of fourteen new cases and a review of the literature |
title_full | Congenital central hypoventilation syndrome in neonates: report of fourteen new cases and a review of the literature |
title_fullStr | Congenital central hypoventilation syndrome in neonates: report of fourteen new cases and a review of the literature |
title_full_unstemmed | Congenital central hypoventilation syndrome in neonates: report of fourteen new cases and a review of the literature |
title_short | Congenital central hypoventilation syndrome in neonates: report of fourteen new cases and a review of the literature |
title_sort | congenital central hypoventilation syndrome in neonates: report of fourteen new cases and a review of the literature |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107878/ https://www.ncbi.nlm.nih.gov/pubmed/34012823 http://dx.doi.org/10.21037/tp-20-303 |
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