Clinical manifestations of ROHHAD(NET) syndrome

	Percent of cases^[1-4]	Typical age of onset^◊[2,4]
Hypothalamic endocrine manifestations
Early- and rapid-onset obesity	100	3 to 7 years
Deceleration of growth rate	38	5 to 14 years
Failed growth hormone stimulation test	62
Adrenal insufficiency	29
Cushing's syndrome	5
Hypernatremia*	62	2 to 12 years
Diabetes insipidus	24	2 to 12 years
Hyperprolactinemia	52	4 to 12 years
Central hypothyroidism	52
Hypogonadotropic hypogonadism	43
Precocious puberty	10
Respiratory manifestations^¶	100
Cardiorespiratory arrest	57	3 to 8 years
Autonomic dysregulation^Δ	52	3 to 13 years
Tumors of neural crest origin	40-56	3 to 7 years
Adrenal ganglioneuroma	29
Neurobehavioral disorders	48	Median 4.8 years

ROHHAD(NET): rapid-onset obesity, hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural crest tumors; SD: standard deviation.
* In this case, hypernatremia was defined as consistent blood sodium concentrations of >145 mEq/L (which is >2 SD for age). Paradoxically, some patients have hyponatremia.
¶ Respiratory manifestations typically consist of hypercarbia and hypoxemia during wakefulness, sometimes associated with cyanotic episodes.
Δ Symptoms of autonomic dysfunction may include episodes of hypo- or hyperthermia (which may be life-threatening) or bradycardia^[3].
◊ ROHHAD(NET) usually presents in early childhood with rapid weight gain (mean 3.1 years), followed by hypothalamic dysfunction (4.0 years), autonomic dysregulation (4.9 years), and lastly, central hypoventilation (5.3 years, or about 2 years after the initial rapid-onset obesity). Up to 56 percent can have neural crest tumors, 70 percent of which were diagnosed within two years of initial rapid weight gain^[4].

Data from:

Bougneres P, Pantalone L, Linglart A, et al. 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.
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.
Chow C, Fortier MV, Das L, et al. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome may have a hypothalamus-periaqueductal gray localization. Pediatr Neurol 2015; 52:521.
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; 105:2119.

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