{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:27:20Z","timestamp":1793039240527,"version":"4.5.0"},"reference-count":46,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2020,5,14]],"date-time":"2020-05-14T00:00:00Z","timestamp":1589414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Context<\/jats:title><jats:p>Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation and neural crest tumor (ROHHHAD[NET]) is a rare and potentially fatal disease. No specific diagnostic biomarker is currently available, making prompt diagnosis challenging. Since its first definition in 2007, a complete clinical analysis leading to specific diagnosis and follow-up recommendations is still missing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The purpose of this work is to describe the clinical timeline of symptoms of ROHHAD(NET) and propose recommendations for diagnosis and follow-up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>We conducted a systematic review of all ROHHAD(NET) case studies and report a new ROHHAD patient with early diagnosis and multidisciplinary care.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>All the articles that meet the definition of ROHHAD(NET) and provide chronological clinical data were reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis individual patient data guidelines. The data were grouped into 7 categories: hypothalamic dysfunction, autonomic dysregulation, hypoventilation, NET, psychiatric symptoms, other clinical manifestations, and outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty-three individual patient data descriptions were analyzed. The timeline of the disease shows rapid-onset obesity followed shortly by hypothalamic dysfunction. Dysautonomia was reported at a median age of 4.95 years and hypoventilation at 5.33 years, or 2.2 years after the initial obesity. A NET was reported in 56% of the patients, and 70% of these tumors were diagnosed within 2 years after initial weight gain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Because early diagnosis improves the clinical management and the prognosis in ROHHAD(NET), this diagnosis should be considered for any child with rapid and early obesity. We propose guidance for systematic follow-up and advise multidisciplinary management with the aim of improving prognosis and life expectancy.<\/jats:p><\/jats:sec>","DOI":"10.1210\/clinem\/dgaa247","type":"journal-article","created":{"date-parts":[[2020,5,15]],"date-time":"2020-05-15T05:47:39Z","timestamp":1589521659000},"page":"2119-2131","source":"Crossref","is-referenced-by-count":67,"title":["ROHHAD(NET) Syndrome: Systematic Review of the Clinical Timeline and Recommendations for Diagnosis and Prognosis"],"prefix":"10.1210","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0127-1668","authenticated-orcid":false,"given":"Julie","family":"Harvengt","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Sart-Tilman (Li\u00e8ge), Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Gernay","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Section Endocrinology, Sart-Tilman (Li\u00e8ge), Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meriem","family":"Mastouri","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Section Pneumology, Sart-Tilman (Li\u00e8ge), Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nesrine","family":"Farhat","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Section Cardiology, Sart-Tilman (Li\u00e8ge), Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christine","family":"Lebrethon","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Section Endocrinology, Sart-Tilman (Li\u00e8ge), Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christine","family":"Seghaye","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Section Cardiology, Sart-Tilman (Li\u00e8ge), Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Bours","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Sart-Tilman (Li\u00e8ge), Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,5,14]]},"reference":[{"key":"2021122116313912200_CIT0001","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1001\/archpedi.1965.02090030165011","article-title":"Primary alveolar hypoventilation syndrome (ONDINE\u2019S curse)","volume":"110","author":"Fishman","year":"1965","journal-title":"Am J Dis Child."},{"issue":"1","key":"2021122116313912200_CIT0002","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1002\/(SICI)1099-0496(200001)29:1<62::AID-PPUL10>3.0.CO;2-M","article-title":"Late-onset central hypoventilation with hypothalamic dysfunction: a distinct clinical syndrome","volume":"29","author":"Katz","year":"2000","journal-title":"Pediatr Pulmonol."},{"issue":"1","key":"2021122116313912200_CIT0003","doi-asserted-by":"crossref","first-page":"e179","DOI":"10.1542\/peds.2006-3324","article-title":"Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation presenting in childhood","volume":"120","author":"Ize-Ludlow","year":"2007","journal-title":"Pediatrics."},{"issue":"10","key":"2021122116313912200_CIT0004","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.1210\/jc.2008-0238","article-title":"Endocrine manifestations of the rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, and neural tumor syndrome in childhood","volume":"93","author":"Bougn\u00e8res","year":"2008","journal-title":"J Clin Endocrinol Metab."},{"issue":"2","key":"2021122116313912200_CIT0005","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1159\/000499163","article-title":"Anti-hypothalamus and anti-pituitary autoantibodies in ROHHAD syndrome: additional evidence supporting an autoimmune etiopathogenesis","volume":"92","author":"Giacomozzi","year":"2019","journal-title":"Horm Res Paediatr."},{"key":"2021122116313912200_CIT0006","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s13023-015-0314-x","article-title":"Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD): exome sequencing of trios, monozygotic twins and tumours","volume":"10","author":"Barclay","year":"2015","journal-title":"Orphanet J Rare Dis."},{"issue":"16","key":"2021122116313912200_CIT0007","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1001\/jama.2015.3656","article-title":"Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data: the PRISMA-IPD statement","volume":"313","author":"Stewart","year":"2015","journal-title":"JAMA."},{"issue":"1","key":"2021122116313912200_CIT0008","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1186\/s13256-016-1116-z","article-title":"Rapid-onset obesity, hypoventilation, hypothalamic dysfunction, autonomic dysregulation and neuroendocrine tumor syndrome with a homogenous enlargement of the pituitary gland: a case report","volume":"10","author":"Aljabban","year":"2016","journal-title":"J Med Case Rep."},{"issue":"1","key":"2021122116313912200_CIT0009","doi-asserted-by":"crossref","first-page":"e12","DOI":"10.4158\/EP12140.CR","article-title":"A case of rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural crest tumor: ROHHADNET syndrome","volume":"19","author":"Abaci","year":"2013","journal-title":"Endocr Pract."},{"issue":"11","key":"2021122116313912200_CIT0010","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.15537\/smj.2016.11.15578","article-title":"Rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation in Saudi Arabia","volume":"37","author":"Al-Harbi","year":"2016","journal-title":"Saudi Med J."},{"key":"2021122116313912200_CIT0011","first-page":"438(Abstract P3-898)","article-title":"A case of rapid onset obesity, hypoventilation, hypothalamic dysregulation and neuroendocrine tumours\u2014ROHHADNET syndrome","volume":"84","author":"Atapattu","year":"2015","journal-title":"Horm Res Paediatr."},{"issue":"1","key":"2021122116313912200_CIT0012","first-page":"e38351","article-title":"Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome: a case report","volume":"5","author":"Bagheri","year":"2017","journal-title":"Arch Pediatr Infect Dis."},{"key":"2021122116313912200_CIT0013","first-page":"427(Abstract P3-d1-1406)","article-title":"Rapid onset obesity, endocrine hypertension and ganglioneuroblastoma intermixed: early manifestation of ROHHAD-NET syndrome? Presentation of two cases. 9th Joint Meeting of Paediatric Endocrinology","volume":"80","author":"Baronio","year":"2013","journal-title":"Horm Res Paediatr."},{"issue":"10","key":"2021122116313912200_CIT0014","doi-asserted-by":"crossref","first-page":"e27906","DOI":"10.1002\/pbc.27906","article-title":"Metastatic neuroblastoma in a patient with ROHHAD: a new alert regarding the risk of aggressive malignancies in this rare condition","volume":"66","author":"Calvo","year":"2019","journal-title":"Pediatr Blood Cancer."},{"issue":"1","key":"2021122116313912200_CIT0015","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1515\/jpem-2015-0129","article-title":"Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome and celiac disease in a 13-year-old girl: further evidence for autoimmunity?","volume":"29","author":"Cemeroglu","year":"2016","journal-title":"J Pediatr Endocrinol Metab."},{"issue":"1","key":"2021122116313912200_CIT0016","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1460-9592.2012.03924.x","article-title":"Anesthetic considerations for rapid-onset obesity, hypoventilation, hypothalamic dysfunction, and autonomic dysfunction (ROHHAD) syndrome in children","volume":"23","author":"Chandrakantan","year":"2013","journal-title":"Paediatr Anaesth."},{"key":"2021122116313912200_CIT0017","doi-asserted-by":"crossref","first-page":"bcr0220102706","DOI":"10.1136\/bcr.02.2010.2706","article-title":"Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD): a case with additional features and review of the literature","volume":"2011","author":"Chew","year":"2011","journal-title":"BMJ Case Rep"},{"issue":"3","key":"2021122116313912200_CIT0018","doi-asserted-by":"crossref","first-page":"e788","DOI":"10.1542\/peds.2012-3225","article-title":"Hypocretin-1 deficiency in a girl with ROHHAD syndrome","volume":"132","author":"Dhondt","year":"2013","journal-title":"Pediatrics."},{"key":"2021122116313912200_CIT0019","first-page":"172(Abstract P2-d2-557)","article-title":"Rapid-onset obesity, hypoventilation,hypothalamic dysfunction, autonomic dysregulation, and neural crest tumour (ROHHADNET) syndrome in two Italian patients: clinical characterization and exome sequencing analysis","volume":"78","author":"Gallizia","year":"2012","journal-title":"Horm Res Paediatr."},{"key":"2021122116313912200_CIT0020","article-title":"The evolving phenotype in a patient with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) and response to caffeine treatment | D41. Interesting cases in pediatric pulmonology","author":"Gordon","year":"2015","journal-title":"Am Thorac Soc Int Conf Meet, Colorado"},{"issue":"4","key":"2021122116313912200_CIT0021","first-page":"222","article-title":"Hypoventilation improvement in an adult non-invasively ventilated patient with rapid-onset obesity with hypothalamic dysfunction hypoventilation and autonomic dysregulation (ROHHAD)","volume":"65","author":"Graziani","year":"2016","journal-title":"Pneumologia."},{"issue":"3","key":"2021122116313912200_CIT0022","first-page":"235","article-title":"Nocturnal anxiety in a youth with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD)","volume":"22","author":"Grudnikoff","year":"2013","journal-title":"J Can Acad Child Adolesc Psychiatry."},{"issue":"9","key":"2021122116313912200_CIT0023","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.nrl.2016.04.008","article-title":"S\u00edndrome ROHHAD (obesidad de r\u00e1pida progresi\u00f3n, disfunci\u00f3n hipotal\u00e1mica, hipoventilaci\u00f3n y disregulaci\u00f3n auton\u00f3mica). Presentaci\u00f3n de un caso y revisi\u00f3n de la literatura","volume":"32","author":"Ib\u00e1\u00f1ez-Mic\u00f3","year":"2017","journal-title":"Neurolog\u00eda."},{"issue":"1","key":"2021122116313912200_CIT0024","doi-asserted-by":"crossref","first-page":"e20151080","DOI":"10.1542\/peds.2015-1080","article-title":"Improved behavior and neuropsychological function in children with ROHHAD after high-dose cyclophosphamide","volume":"138","author":"Jacobson","year":"2016","journal-title":"Pediatrics."},{"key":"2021122116313912200_CIT0025","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40842-019-0082-y","article-title":"Natural history of ROHHAD syndrome: development of severe insulin resistance and fatty liver disease over time","volume":"5","author":"Jalal Eldin","year":"2019","journal-title":"Clin Diabetes Endocrinol."},{"issue":"4","key":"2021122116313912200_CIT0026","doi-asserted-by":"crossref","first-page":"254","DOI":"10.4274\/jcrpe.1432","article-title":"ROHHAD syndrome: reasons for diagnostic difficulties in obesity","volume":"6","author":"Kocaay","year":"2014","journal-title":"J Clin Res Pediatr Endocrinol."},{"issue":"2","key":"2021122116313912200_CIT0027","doi-asserted-by":"crossref","first-page":"226","DOI":"10.5603\/EP.a2016.0037","article-title":"ROHHAD in a 9-year-old boy\u2014clinical case","volume":"67","author":"Kot","year":"2016","journal-title":"Endokrynol Pol."},{"key":"2021122116313912200_CIT0028","doi-asserted-by":"crossref","first-page":"A119","DOI":"10.1136\/archdischild-2012-301885.284","article-title":"Two children with rapid onset obesity combined with respiratory and endocrine dysfunction. Do they have ROHHAD?","volume":"97","author":"Lucas-Herald","year":"2012","journal-title":"Arch Dis Child."},{"issue":"6","key":"2021122116313912200_CIT0029","doi-asserted-by":"crossref","first-page":"e26983","DOI":"10.1002\/pbc.26983","article-title":"Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation associated with neuroblastoma","volume":"65","author":"Lim","year":"2018","journal-title":"Pediatr Blood Cancer."},{"issue":"3","key":"2021122116313912200_CIT0030","doi-asserted-by":"crossref","first-page":"e711","DOI":"10.1542\/peds.2011-0155","article-title":"Monozygotic twins discordant for ROHHAD phenotype","volume":"128","author":"Patwari","year":"2011","journal-title":"Pediatrics."},{"issue":"2","key":"2021122116313912200_CIT0031","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.jpeds.2010.07.006","article-title":"Cyclophosphamide for rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome","volume":"158","author":"Paz-Priel","year":"2011","journal-title":"J Pediatr."},{"issue":"4","key":"2021122116313912200_CIT0032","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s13312-016-0849-5","article-title":"ROHHAD syndrome: the girl who forgets to breathe","volume":"53","author":"Sanklecha","year":"2016","journal-title":"Indian Pediatr."},{"issue":"3","key":"2021122116313912200_CIT0033","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1177\/0883073812469050","article-title":"Intrathecal synthesis of oligoclonal bands in rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome: new evidence supporting immunological pathogenesis","volume":"29","author":"Sartori","year":"2014","journal-title":"J Child Neurol."},{"issue":"2","key":"2021122116313912200_CIT0034","doi-asserted-by":"crossref","first-page":"e586","DOI":"10.1542\/peds.2013-2582","article-title":"ROHHADNET syndrome presenting as major behavioral changes in a 5-year-old obese girl","volume":"134","author":"Sethi","year":"2014","journal-title":"Pediatrics."},{"issue":"4","key":"2021122116313912200_CIT0035","first-page":"382","article-title":"ROHHAD syndrome, a rare cause of hypothalamic obesity: report of two cases","volume":"10","author":"\u015eiraz","year":"2018","journal-title":"J Clin Res Pediatr Endocrinol."},{"issue":"1","key":"2021122116313912200_CIT0036","doi-asserted-by":"crossref","first-page":"47","DOI":"10.4038\/cmj.v57i1.4205","article-title":"Rapid onset obesity, hypoventilation, hypothalamic, autonomic and thermal dysregulation, and neural tumour (ROHHADNET) syndrome presenting with Cushing syndrome","volume":"57","author":"Sumanasena","year":"2012","journal-title":"Ceylon Med J."},{"key":"2021122116313912200_CIT0037","first-page":"241(Abstract P2-d3-771)","article-title":"A case of rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation: ROHHAD syndrome. 9th Joint Meeting of Paediatric Endocrinology","volume":"80","author":"Ucar","year":"2013","journal-title":"Horm Res Paediatr."},{"key":"2021122116313912200_CIT0038","first-page":"230 (Abstract P2-384)","article-title":"Obesity in ROHHADNET syndrome: does cortisol play a role?","volume":"84","author":"Van Tellingen","year":"2015","journal-title":"Horm Res Paediatr."},{"issue":"1","key":"2021122116313912200_CIT0039","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s13023-018-0860-0","article-title":"ROHHAD and Prader-Willi syndrome (PWS): clinical and genetic comparison","volume":"13","author":"Barclay","year":"2018","journal-title":"Orphanet J Rare Dis."},{"key":"2021122116313912200_CIT0040","doi-asserted-by":"crossref","first-page":"j1863","DOI":"10.1136\/bmj.j1863","article-title":"Neuroblastoma","volume":"357","author":"Shohet","year":"2017","journal-title":"BMJ."},{"issue":"2","key":"2021122116313912200_CIT0041","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1148\/rg.2018170132","article-title":"Updates in diagnosis, management, and treatment of neuroblastoma","volume":"38","author":"Swift","year":"2018","journal-title":"Radiographics."},{"issue":"4","key":"2021122116313912200_CIT0042","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1097\/MOP.0000000000000118","article-title":"Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation: review and update","volume":"26","author":"Patwari","year":"2014","journal-title":"Curr Opin Pediatr."},{"issue":"4","key":"2021122116313912200_CIT0043","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1203\/PDR.0b013e318229474d","article-title":"Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation: analysis of hypothalamic and autonomic candidate genes","volume":"70","author":"Rand","year":"2011","journal-title":"Pediatr Res."},{"key":"2021122116313912200_CIT0044","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.resp.2015.11.002","article-title":"Absence of mutations in HCRT, HCRTR1 and HCRTR2 in patients with ROHHAD","volume":"221","author":"Barclay","year":"2016","journal-title":"Respir Physiol Neurobiol."},{"issue":"5","key":"2021122116313912200_CIT0045","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1210\/jc.2014-4215","article-title":"Whole exome sequencing identifies RAI1 mutation in a morbidly obese child diagnosed with ROHHAD syndrome","volume":"100","author":"Thaker","year":"2015","journal-title":"J Clin Endocrinol Metab."},{"key":"2021122116313912200_CIT0046","doi-asserted-by":"crossref","first-page":"1250721","DOI":"10.1155\/2018\/1250721","article-title":"Rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, and neuroendocrine tumors (ROHHADNET) syndrome: a systematic review","volume":"2018","author":"Lee","year":"2018","journal-title":"Biomed Res Int."}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgaa247\/33213243\/dgaa247.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/105\/7\/2119\/41840822\/jcem_105_7_2119.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/105\/7\/2119\/41840822\/jcem_105_7_2119.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T03:41:02Z","timestamp":1696131662000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/105\/7\/2119\/5837124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,14]]},"references-count":46,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,5,14]]},"published-print":{"date-parts":[[2020,7,1]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgaa247","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,7]]},"published":{"date-parts":[[2020,5,14]]}}}