ROHHADNET (rapid-onset obesity with hypoventilation, hypothalamic dysfunction, autonomic dysregulation and a neuroendocrine tumor) as a rare cause of child obesity presenting with behavioral change

*Correspondence: [e-mail].

Abstract

Case Presentation: A previously healthy child developed hyperphagia and rapid weight gain at the age of 3 years. By the age of 4, she met criteria for infantile obesity and started to present social withdrawal, poor school performance and a flat affect. By the age of 6, during investigation for secondary causes of obesity, paravertebral ganglioneuroblastoma was found. She was submitted to surgical resection with no complications, but later developed severe hypoventilation episodes aiding intubation until a tracheostomy was performed. Polysomnography studies revealed a central apnea pattern and BiPAP was installed. She also developed multiple episodes of hyponatremia due to insipidus diabetes and also frequent episodes of hypothermia, meeting the clinical criteria for ROHHADNET (Rapid-onset Obesity with Hypoventilation, Hypothalamic Dysfunction, Autonomic Dysregulation neuroendocrine tumor). Due to these findings, new generation sequencing of PHOX2B gene that encodes paired-like homeobox protein 2B was performed, but no pathogenic variants were found. Treatment with modafinil, bupropion and desmopressin acetate were iniciated and behaviour and endocrinological symptoms improved.

Discussion: Rapid onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) syndrome is a rare disease and less than 200 cases are described in literature. In approximately 40–56% of cases there is an association with tumors with neural crest origin, and this has included the termination NET into the acronym ROHHADNET. The etiopathogeny includes genetic, epigenetic, and autoimmune factors. Several candidate genes for this study are being studied, and the main candidate gene is PHOX2B. The autoimmune theory is based on concurring neural crest origin tumors, given that they are usually associated with other autoimmune-mediated paraneoplastic syndromes. Treatment is based on multidisciplinary care for obesity, respiratory assessment, hypothalamic dysfunctions, dysautonomia and behavior symptoms.

Final Comments: We recommend that screening for neural crest tumors should always be performed early in patients with rapid obesity, hypothalamic dysfunction accompanied by personality changes and developmental regression. Prompt recognition and timely application of respiratory support may prevent grave complications leading to unprepared mortality.

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Artikel online veröffentlicht:
12. Mai 2025