ROHHAD-NET Syndrome
A Case Series
DOI:
https://doi.org/10.15605/jafes.040.01.10Keywords:
ROHHAD, obesity, central hypoventilation, neural crest tumorAbstract
Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation and neural crest tumor (ROHHAD-NET) though a rare disease, is potentially fatal. It is of utmost importance to be understood and urgently diagnosed. We hereby report a series of three cases, the first of its kind from India. Children older than 18 months old usually exhibit rapid weight growth as a presenting symptom. Hypothalamic dysfunction could lead to endocrine issues, respiratory dysfunction and autonomic dysregulation. Over the years, with variable timing, one or more signs of hypothalamic dysfunction appear: hyperprolactinemia, growth hormone deficiency, central hypothyroidism, central adrenal insufficiency or Cushing syndrome, early or delayed puberty, water-electrolyte balance disorders. The diagnosis is difficult because there is no reliable test, and the treatment is mainly supportive. All the three children who were thriving well, presented with rapid weight gain and then developed symptoms of hypothalamic dysfunction. While in one a neural crest tumor was incidentally detected, the second had persistent hypernatremia and the third child presented with intestinal obstruction. The varied presentation and vague symptom spectrum exhibit a diagnostic challenge to the clinician and underscores the importance of creating awareness. An individualized strategic approach is needed as it is clinically difficult to distinguish ROHHAD syndrome from other obesity syndromes of genetic origin.
Downloads
References
1. Fishman LS, Samson JH, Sperling DR. Primary alveolar hypoventilation syndrome (ONDINE’S curse). Am J Dis Child. 1965;110:155-161. https://pubmed.ncbi.nlm.nih.gov/14320765 https://doi.org/10.1001/archpedi.1965.02090030165011
2. Lee JM, Shin J, Kim S, et al. Rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, and neuroendocrine Tumors (ROHHADNET) syndrome: A Systematic Review. Biomed Res Int. 2018;2018:1250721. Phttps://pubmed.ncbi.nlm.nih.gov/30584530 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280256 https://doi.org/10.1155/2018/1250721
3. Ize-Ludlow D, Gray JA, Sperling MA, et al. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation presenting in childhood. Pediatrics. 2007;120(1):e179-88. https://pubmed.ncbi.nlm.nih.gov/17606542 https://doi.org/10.1542/peds.2006-3324
4. Harvengt J, Gernay C, Mastouri M, et al. ROHHAD (NET) syndrome: Systematic review of the clinical timeline and recommendations for diagnosis and prognosis. J Clin Endocrinol Metab. 2020;105(7):dgaa247. https://pubmed.ncbi.nlm.nih.gov/32407531 https://doi.org/10.1210/clinem/dgaa247
5. Abaci A, Catli G, Bayram E, et al. A case of rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural crest tumor: ROHHADNET syndrome. Endocr Pract. 2013;19(1):e12-6. https://pubmed.ncbi.nlm.nih.gov/23186956 https://doi.org/10.4158/EP12140.CR
6. Patwari PP, Rand CM, Berry-Kravis EM, Ize-Ludlow D, Weese-Mayer DE. Monozygotic twins discordant for ROHHAD phenotype. Pediatrics. 2011;128(3):e711-5. https://pubmed.ncbi.nlm.nih.gov/21807698 https://doi.org/10.1542/peds.2011-0155
7. Desse B, Tran A, Butori M, et al. ROHHAD syndrome without rapid-onset obesity: A diagnosis challenge. Front Pediatr. 2022;10:910099. https://pubmed.ncbi.nlm.nih.gov/36120648 https://doi.org/10.3389/fped.2022.910099
8. Sirvent N, Bérard E, Chastagner P, Feillet F, Wagner K, Sommelet D. Hypothalamic dysfunction associated with neuroblastoma: Evidence for a new Paraneoplastic syndrome? Med Pediatr Oncol. 2003;40(5):326-328. https://pubmed.ncbi.nlm.nih.gov/12652624 DOI: 10.1002/mpo.10157
9. Giacomozzi C, Guaraldi F, Cambiaso P, et al. Anti-hypothalamus and anti-pituitary auto-antibodies in ROHHAD Syndrome: Additional evidence supporting an autoimmune etiopathogenesis. Horm Res Paediatr. 2019;92(2):124-32. Phttps://pubmed.ncbi.nlm.nih.gov/31039576. https://doi.org/10.1159/000499163
10. Grossi A, Rusmini M, Cusano R, et al. Whole genome sequencing in ROHHAD trios proved inconclusive: What's beyond? Front Genet. 2023;14:1031074. https://pubmed.ncbi.nlm.nih.gov/37609037 https://doi.org/10.3389/fgene.2023.1031074
11. Lazea C, Sur L, Florea M. ROHHAD (Rapid-onset Obesity with Hypoventilation, Hypothalamic Dysfunction, Autonomic Dysregulation) syndrome - What every pediatrician should know about the etiopathogenesis, diagnosis and treatment: A Review. Int J Gen Med. 2021;14:319-26. https://pubmed.ncbi.nlm.nih.gov/33542648 https://doi.org/10.2147/IJGM.S293377
12. Thaker VV, Esteves KM, Towne MC, et al. Whole exome sequencing identifies RAI1 mutation in a morbidly obese child diagnosed with ROHHAD syndrome. J Clin Endocrinol Metab. 2015;100(5):1723-1730. https://pubmed.ncbi.nlm.nih.gov/25781356 https://doi.org/10.1210/jc.2014-4215
13. Dhondt K, Verloo P, Verhelst H, Van Coster R, Overeem S. Hypocretin-1 deficiency in a girl with ROHHAD syndrome. Pediatrics. 2013;132(3):e788-92. https://pubmed.ncbi.nlm.nih.gov/23940246 https://doi.org/10.1542/peds.2012-3225
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Dhanya Soodhana, Manjula Subramaniya Iyer, Joe George, Vimal Mavila Veetil, Preetha Remesh, Kesavan Melarcode Ramanan, Binesh Arayullathil, Abraham Mammen
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The full license text is available at: http://creativecommons.org/licenses/by-nc/3.0/legalcode.
To request permission to translate, reproduce, download, or use articles or images for commercial reuse or business purposes from the Journal of the ASEAN Federation of Endocrine Societies (JAFES), kindly complete the Permission Request for Use of Copyrighted Material Form and email jafes@asia.com or jafes.editor@gmail.com.
A written agreement will be issued to the requester once permission has been granted.
