{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T23:11:41Z","timestamp":1788909101496,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R03TR003869"],"award-info":[{"award-number":["R03TR003869"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n Introduction<\/jats:title>\n \n CCHS is a rare disorder caused by\n PHOX2B<\/jats:italic>\n gene variants. While CCHS hallmarks are hypoventilation and respiratory control dysfunction necessitating lifelong artificial ventilatory support, affected individuals also experience widespread, but less studied, autonomic nervous system (ANS) dysregulation.\n PHOX2B<\/jats:italic>\n variants may be divided into moderate and severe groups based upon molecular and in silico data. The International CCHS Registry is a secure repository for longitudinal data from individuals with a\n PHOX2B<\/jats:italic>\n variant\u2010confirmed diagnosis, including information on seven systems served by the ANS (cardiovascular, gastrointestinal, neurological, ophthalmologic, renal\/urinary, respiratory, sudomotor). Our objective was to analyze patient\u2010reported symptoms (PRS) across all ANS\u2010served systems and determine their relationship with\n PHOX2B<\/jats:italic>\n variant severity. We hypothesized an increase in PRS in all organ systems in individuals with severe variants.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This study analyzed completed initial surveys. Descriptive statistics were generated for all PRS, and by\n PHOX2B<\/jats:italic>\n variant groups, with statistical comparison using the Wilcoxon Rank\u2010Sum and Fisher's exact tests with Benjamini\u2010Hochberg correction.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Analysis of 148 surveys confirmed broad, multi\u2010system ANS dysfunction in CCHS. Those with severe\n PHOX2B<\/jats:italic>\n variants were more likely to report cardiovascular, gastrointestinal, neurological, respiratory, and ophthalmological\n system<\/jats:italic>\n dysfunction compared to individuals with moderate variants. Individuals with severe\n PHOX2B<\/jats:italic>\n variants reported significantly more\n symptoms<\/jats:italic>\n in 6\/7 organ systems than those with moderate variants.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The individual\u2010reported impact of CCHS varies by both\n PHOX2B<\/jats:italic>\n variant severity and the ANS organ system\/symptom manifestations. Beyond the traditional clinical focus on cardiorespiratory dysfunction, these results highlight other ANS\u2010related systems that are critical for comprehensive clinical management and future therapeutic trial design.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/ppul.71619","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T06:10:03Z","timestamp":1776233403000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["International Congenital Central Hypoventilation Syndrome (CCHS) Registry: Analysis of Patient\u2010Reported Symptoms by\n PHOX2B<\/i>\n Variant"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1383-3156","authenticated-orcid":false,"given":"Delaney R.","family":"Vandemore","sequence":"first","affiliation":[{"name":"Center for Autonomic Medicine in Pediatrics (CAMP), Department of Pediatrics Ann & Robert H. Lurie Children's Hospital of Chicago and Stanley Manne Children's Research Institute Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin K.","family":"Lonergan","sequence":"additional","affiliation":[{"name":"Center for Autonomic Medicine in Pediatrics (CAMP), Department of Pediatrics Ann & Robert H. Lurie Children's Hospital of Chicago and Stanley Manne Children's Research Institute Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey M.","family":"Rand","sequence":"additional","affiliation":[{"name":"Center for Autonomic Medicine in Pediatrics (CAMP), Department of Pediatrics Ann & Robert H. Lurie Children's Hospital of Chicago and Stanley Manne Children's Research Institute Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra E.","family":"Weese\u2010Mayer","sequence":"additional","affiliation":[{"name":"Center for Autonomic Medicine in Pediatrics (CAMP), Department of Pediatrics Ann & Robert H. Lurie Children's Hospital of Chicago and Stanley Manne Children's Research Institute Chicago Illinois USA"},{"name":"Departments of Pediatrics and Neurology Northwestern University Feinberg School of Medicine Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200807-1069ST"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2011.38"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.23236"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20527"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2016.196"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.015412"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200602-305OC"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.20744"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/428366"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-021-01178-x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1249"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.10438"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.71072"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20040282"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi401"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.25973"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-022-00901-1"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.21170"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.15-0402"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-020-01460-2"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.20366"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20565"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00863.2004"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-015-0241-3"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.71012"}],"container-title":["Pediatric Pulmonology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ppul.71619","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ppul.71619","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ppul.71619","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T11:33:01Z","timestamp":1780313581000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ppul.71619"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/ppul.71619"],"URL":"https:\/\/doi.org\/10.1002\/ppul.71619","archive":["Portico"],"relation":{},"ISSN":["8755-6863","1099-0496"],"issn-type":[{"value":"8755-6863","type":"print"},{"value":"1099-0496","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-11-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71619"}}