Rapid onset obesity and ondine’s curse: a deadly syndrome

Authors

  • Shalini Akunuri Department of Pediatric Critical Care, Diabetes and Bariatric Medicine, Narayana Health, Bangalore, Karnataka, India
  • Dinesh Kumar Vuppu Department of Pediatrics, Diabetes and Bariatric Medicine, Narayana Health, Bangalore, Karnataka, India
  • Anil Kumar Sapare Department of Pediatric Critical Care, Diabetes and Bariatric Medicine, Narayana Health, Bangalore, Karnataka, India
  • Abhijith Bagde Department of Pediatric Critical Care, Diabetes and Bariatric Medicine, Narayana Health, Bangalore, Karnataka, India
  • Rashmi Vasudeva Murthy Department of Pediatrics, Diabetes and Bariatric Medicine, Narayana Health, Bangalore, Karnataka, India
  • Subramanian Kannan Department of Endocrinology, Diabetes and Bariatric Medicine, Narayana Health, Bangalore, Karnataka, India

DOI:

https://doi.org/10.18203/2349-3291.ijcp20171739

Keywords:

Hypothalamic dysfunction, Hypoventilation, Neural crest tumor, Rapid onset obesity

Abstract

ROHHADNET syndrome is characterized by rapid-onset-obesity, hypoventilation, hypothalamic dysregulation, autonomic dysfunction and neural tumors. A 2.4-year-old girl presented with inability to be aroused from sleep. She was obese, obtunded, hypoventilating with severe hypercarbia. Non-invasive ventilation (NIV) was started following which her sensorium, hypercarbia normalized. History revealed hyperphagia, rapidly increasing weight after 1½ year of age with normal height centiles. Hormonal profile revealed hyperprolactinemia, central hypothyroidism, suboptimal growth hormone response and normal cortisol. She had presacral tumor, pain insensitivity, fluctuating blood pressure, constipation and strabismus. ROHHADNET syndrome was clinically diagnosed based on constellation of these features. She was discharged on nocturnal NIV. Over 8 months, her hypoventilation progressed requiring tracheostomy. She also underwent excision of the presacral tumor which proved to be ganglioneuroma. Whole exome sequencing was negative for CCHS and ROHHAD genes, which could be due to somatic mosaicism; variation in the genomic region not covered by the test; or large insertions, deletions, complex rearrangements. Arriving at the diagnosis is difficult due to its overlap with other hyperphagic obesity syndromes and lack of confirmatory genetic testing.

References

Ize-Ludlow D, Gray JA, Sperling MA, Berry-Kravis EM, Milunsky JM, Farooqi IS, et al. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation presenting in childhood. Pediatrics. 2007;120:179-88.

De Pontual L, Trochet D, Caillat-Zucman S, Abou Shenab OA, Bougneres P, Crow Y, et al. Delineation of late onset hypoventilation associated with hypothalamic dysfunction syndrome. Pediatr Res. 2008;64:689-94.

Onal H, Ersen A. A case of late-onset central hypoventilation syndrome with hypothalamic dysfunction: through a new phenotype. Turk J Pediatr. 2010;52:198-202.

Patwari PP, Rand CM, Berry-Kravis EM, Ize-Ludlow D, Weese-Mayer DE. Monozygotic twins discordant for ROHHAD phenotype. Pediatrics. 2011;128:711-5.

Fishman LS, Samson JH, Sperling DR. Primary Alveolar Hypoventilation Syndrome (Ondine's Curse). Am J Dis Child. 1965;110:155-61.

Bougneres P, Pantalone L, Linglart A, Rothenbuhler A, Le Stunff C. Endocrine manifestations of the rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, and neural tumor syndrome in childhood. J Clin Endocrinol Metab. 2008;93:3971-80.

Sirvent N, Berard E, Chastagner P, Feillet F, Wagner K, Sommelet D. Hypothalamic dysfunction associated with neuroblastoma: evidence for a new Paraneoplastic syndrome? Med Pediatr Oncol. 2003;40:326-8.30

Abaci A, Catli G, Bayram E, Koroglu T, Olgun HN, Mutafoglu K, et al. A case of rapidonset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural crest tumor: ROHHADNET syndrome. Endocr Pract. 2013;19:12-6.

Rand CM, Patwari PP, Rodikova EA, Zhou L, Berry-Kravis EM, Wilson RJ, et al. Rapidonset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation: analysis of hypothalamic and autonomic candidate genes. Pediatr Res. 2011;70:375-8.

Farooqi IS, O'Rahilly S. Monogenic obesity in humans. Annu Rev Med. 2005;56:443-58.

Govaerts C, Srinivasan S, Shapiro A, Zhang S, Picard F, Clement K, et al. Obesityassociated mutations in the melanocortin 4 receptor provide novel insights into its function. Peptides. 2005;26:1909-19.

North KN, Ouvrier RA, McLean CA, Hopkins IJ. Idiopathic hypothalamic dysfunction with dilated unresponsive pupils: report of two cases. J Child Neurol. 1994;9:320-5.

Nunn K, Ouvrier R, Sprague T, Arbuckle S, Docker M. Idiopathic hypothalamic dysfunction: a paraneoplastic syndrome? J Child Neurol 1997;12:276-81.

Katz ES, McGrath S, Marcus CL. Late-onset central hypoventilation with hypothalamic dysfunction: a distinct clinical syndrome. Pediatr Pulmonol. 2000;29:62-8.

Chew HB, Ngu LH, Keng WT. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD): a case with additional features and review of the literature. BMJ Case Rep. 2011;2011;10.

Thaker VV, Esteves KM, Towne MC, Brownstein CA, James PM, Crowley L, et al. Whole exome sequencing identifies RAI1 mutation in a morbidly obese child diagnosed with ROHHAD syndrome. J Clin Endocrinol Metab. 2015;100:1723-30.

Barclay SF, Rand CM, Borch LA, Nguyen L, Gray PA, Gibson WT et al. rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD): exome sequencing of trios, monozygotic twins and tumours. Orphanet J Rare Dis. 2015;10:103.

Downloads

Published

2017-04-25

Issue

Section

Case Reports