ESPE Yearbook of Paediatric Endocrinology

J Clin Endocrinol Metab. 2020 Jul 1;105(7):dgaa247. 10.1210/clinem/dgaa247. https://pubmed.ncbi.nlm.nih.gov/32407531/

Based on a structured summary of a case series of 43 well-defined patients, these authors propose for regular screening and preventive examinations in ROHHAD patients and list the therapeutic options. Although these recommendations are not strictly evidence-based, they are a very valuable support for paediatric endocrinologists and other clinicians who provide care for ROHHAD patients.

ROHHAD(NET) syndrome is a rare obesity syndrome with a high mortality due to cardiovascular arrest. The symptom complex of ROHHAD(NET) syndrome was first described in 2007 (1). Main features include: hyperphagia and obesity, hypoventilation, disorders of temperature and water balance, and other disorders of hypothalamic function, including endocrine deficits, disorders of psychomotor development and tumours of the neural crest. Its cause is unknown, and no aetiology-based therapy is available (2, 3, 4).

Despite the life-threatening complications of ROHHAD(NET), there existed neither clear recommendations for diagnosis nor for the regular screening and preventive examinations. Here, Harvengt et al. meet this challenge and supplement their own case report with a systematic literature review. Two points are noteworthy. First, the authors use the narrow, original definition of ROHHAD(NET) (1) to identify cases and case series of clearly affected patients. Secondly, they use the PRISMA individual patient guideline methodology to analyse chronological clinical data and to identify a characteristic time course of the development of the syndrome. Their analysis of 43 ROHHAD patients shows a median age at onset of excessive weight gain of 3.1 years, followed by a diagnosis of autonomic dysregulation (median age 4.95 years) and central hypoventilation (median age 5.3 years). Overall, 83% of the analysed patients were affected by hypoventilation within the first five years after onset of rapid weight gain. The cumulative data on the occurrence of neural crest tumours are particularly interesting. Overall, 56% received a tumour diagnosis, the majority of which were ganglioneuromas, but also neuroblastomas. In 70% of affected patients, the tumour occurred within 2 years after the onset of weight gain, so there is possibly an age dependency of the tumour risk.

References: 1. 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:e179–e188.2. BougnÒres P, Pantalone L, Linglart A, Rothenbühler A, Le Stunff C. Endocrine manifestations of the rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, and neural tumor syndrome in childhood. JCEM 2008; 93:3971–80.3. Paz-Priel I, Cooke DW, Chent AR. Cyclophosphamide for rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome. J Pediatr 2011; 158:337–9.4. Ouvrier R, Nunn K, Sprague T, McLean C, Arbuckle S, Hopkins I, North K. Idiopathic hypothalamic dysfunction: a paraneoplastic syndrome? Lancet 1995; 346(8985):1298.