{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T16:53:06Z","timestamp":1793033586557,"version":"4.5.0"},"reference-count":21,"publisher":"BMJ","funder":[{"DOI":"10.13039\/501100000810","name":"Executive Agency for Health and Consumers","doi-asserted-by":"publisher","award":["Project ID 2008 12 06"],"award-info":[{"award-number":["Project ID 2008 12 06"]}],"id":[{"id":"10.13039\/501100000810","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Thorax"],"accepted":{"date-parts":[[2026,5,9]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Congenital central hypoventilation syndrome (CCHS) is a rare disorder characterised by autonomic dysfunction and impaired respiratory control. While advances in ventilatory support have improved survival, risk factors for mortality remain incompletely understood. Our objective was to investigate the impact of genetic and clinical parameters on mortality in children and young adults with genetically confirmed CCHS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data were collected from the European CCHS Consortium registry, encompassing patient information collected from 2012 to 2021. This dataset included information for 240 patients with genetically confirmed CCHS. Complete outcome data were available for 211 patients. Survival outcomes were analysed using Kaplan-Meier curves and Cox proportional hazards regression models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The overall mortality rate was 14% (95% CI 9% to 19%), with most deaths occurring in early childhood. The 25-year survival probability was 89% (95% CI 79% to 100%) for children and young adults with isolated CCHS, compared with 26% (95% CI 6% to 100%) for those with CCHS and Hirschsprung disease (HSCR), corresponding to a 6.8-fold increased risk of mortality (95%\u2009CI 2.2 to 21.1) associated with HSCR. In multivariable Cox models including genotype and HSCR as covariates, mortality risk was consistently associated with HSCR. While respiratory signs at initial presentation were comparable between groups, children with both CCHS and HSCR exhibited signs of more severe autonomic dysfunction, requiring more frequent resuscitation and intubation at birth.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HSCR is a key determinant of increased mortality in children with CCHS, likely because of its association with more extensive autonomic dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/thorax-2025-224512","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:00:25Z","timestamp":1780570825000},"page":"thorax-2025-224512","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Survival in congenital central hypoventilation syndrome (CCHS): data from the European CCHS Consortium"],"prefix":"10.1136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0604-2482","authenticated-orcid":false,"given":"Plamen","family":"Bokov","sequence":"first","affiliation":[{"name":"Service de Physiologie P\u00e9diatrique-Centre du Sommeil-CRMR Hypoventilations alv\u00e9olaires rares, H\u00f4pital Robert Debr\u00e9, Paris, France"},{"name":"Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"NeuroDiderot, INSERM, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiota","family":"Chaitidou-Kolb","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ordenskliniken M\u00fcnchen-Passau, gGmbH, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Dudoignon","sequence":"additional","affiliation":[{"name":"Service de Physiologie P\u00e9diatrique-Centre du Sommeil-CRMR Hypoventilations alv\u00e9olaires rares, H\u00f4pital Robert Debr\u00e9, Paris, France"},{"name":"NeuroDiderot, INSERM, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Giovanna","family":"Paglietti","sequence":"additional","affiliation":[{"name":"Pediatric Pulmonology & Cystic Fibrosis Unit, Respiratory Research Unit, Bambino Gesu Pediatric Hospital, IRCCS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Madureira","sequence":"additional","affiliation":[{"name":"Unidade de Pneumologia e Laborat\u00f3rio do Sono e Ventila\u00e7\u00e3o, Centro Hospitalar e Universitario de Coimbra EPE, Hospital Pedi\u00e1trico de Coimbra, Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Angeles","family":"Garcia-Teresa","sequence":"additional","affiliation":[{"name":"Pediatric Intensive Care Unit, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Madrid, Spain"},{"name":"Home Ventilation Unit, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2786-0812","authenticated-orcid":false,"given":"Christophe","family":"Delclaux","sequence":"additional","affiliation":[{"name":"Service de Physiologie P\u00e9diatrique-Centre du Sommeil-CRMR Hypoventilations alv\u00e9olaires rares, H\u00f4pital Robert Debr\u00e9, Paris, France"},{"name":"Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"NeuroDiderot, INSERM, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9811-8335","authenticated-orcid":false,"given":"Martin","family":"Samuels","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Great Ormond Street Hospital, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"2026060404001550000_thorax-2025-224512v1.1","doi-asserted-by":"crossref","DOI":"10.1186\/s13023-020-01460-2","article-title":"Guidelines for diagnosis and management of congenital central hypoventilation syndrome","volume":"15","author":"Trang","year":"2020","journal-title":"Orphanet J Rare Dis"},{"key":"2026060404001550000_thorax-2025-224512v1.2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20527"},{"key":"2026060404001550000_thorax-2025-224512v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/ng1130"},{"key":"2026060404001550000_thorax-2025-224512v1.4","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200807-1069ST"},{"key":"2026060404001550000_thorax-2025-224512v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(05)83038-0"},{"key":"2026060404001550000_thorax-2025-224512v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(05)80901-1"},{"key":"2026060404001550000_thorax-2025-224512v1.7","doi-asserted-by":"publisher","DOI":"10.1378\/chest.127.1.72"},{"key":"2026060404001550000_thorax-2025-224512v1.8","doi-asserted-by":"crossref","DOI":"10.1177\/11795565231169556","article-title":"Congenital Central Hypoventilation Syndrome: Diagnosis and Long-Term Ventilatory Outcomes","volume":"17","author":"Fain","year":"2023","journal-title":"Clin Med Insights Pediatr"},{"key":"2026060404001550000_thorax-2025-224512v1.9","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.anpedi.2016.05.008","article-title":"Spanish patients with central hypoventilation syndrome included in the European Registry. The 2015 data","volume":"86","author":"Garc\u00eda Teresa","year":"2017","journal-title":"An Pediatr (Barc)"},{"key":"2026060404001550000_thorax-2025-224512v1.10","doi-asserted-by":"crossref","DOI":"10.1007\/s00431-025-05969-1","article-title":"European central hypoventilation syndrome consortium description of congenital central hypoventilation syndrome neonatal onset","volume":"184","author":"Dudoignon","year":"2025","journal-title":"Eur J Pediatr"},{"key":"2026060404001550000_thorax-2025-224512v1.11","doi-asserted-by":"publisher","DOI":"10.1203\/01.pdr.0000191814.73340.1d"},{"key":"2026060404001550000_thorax-2025-224512v1.12","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200707-1079OC"},{"key":"2026060404001550000_thorax-2025-224512v1.13","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2288-9-57","article-title":"Combining estimates of interest in prognostic modelling studies after multiple imputation: current practice and guidelines","volume":"9","author":"Marshall","year":"2009","journal-title":"BMC Med Res Methodol"},{"key":"2026060404001550000_thorax-2025-224512v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-021-01178-x"},{"key":"2026060404001550000_thorax-2025-224512v1.15","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1007\/s00383-017-4150-z","article-title":"Mortality in Swedish patients with Hirschsprung disease","volume":"33","author":"L\u00f6f Granstr\u00f6m","year":"2017","journal-title":"Pediatr Surg Int"},{"key":"2026060404001550000_thorax-2025-224512v1.16","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi401"},{"key":"2026060404001550000_thorax-2025-224512v1.17","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1007\/s00431-023-05339-9","article-title":"Characteristics and outcomes in children with congenital central hypoventilation syndrome on long-term mechanical ventilation in the Netherlands","volume":"183","author":"Evers-Bikker","year":"2024","journal-title":"Eur J Pediatr"},{"key":"2026060404001550000_thorax-2025-224512v1.18","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1016\/j.jpedsurg.2019.02.014","article-title":"Congenital central hypoventilation syndrome and Hirschsprung disease: A retrospective review of the French National Registry Center on 33 cases","volume":"54","author":"Broch","year":"2019","journal-title":"J Pediatr Surg"},{"key":"2026060404001550000_thorax-2025-224512v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2010.06.012"},{"key":"2026060404001550000_thorax-2025-224512v1.20","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63401"},{"key":"2026060404001550000_thorax-2025-224512v1.21","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.01404-2021","article-title":"ERS statement on paediatric long-term noninvasive respiratory support","volume":"59","author":"Fauroux","year":"2022","journal-title":"Eur Respir J"}],"container-title":["Thorax"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/thorax-2025-224512","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:00:27Z","timestamp":1780570827000},"score":1,"resource":{"primary":{"URL":"https:\/\/thorax.bmj.com\/lookup\/doi\/10.1136\/thorax-2025-224512"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,4]]},"references-count":21,"alternative-id":["10.1136\/thorax-2025-224512"],"URL":"https:\/\/doi.org\/10.1136\/thorax-2025-224512","relation":{},"ISSN":["0040-6376","1468-3296"],"issn-type":[{"value":"0040-6376","type":"print"},{"value":"1468-3296","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,4]]}}}