Dados do Trabalho

Título

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.

Apresentação do caso

A previous 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, a 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 was iniciated and behaviour and endocrinological symptoms improved.

Discussão

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 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.

Comentários finais

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.

Referências (se houver)

1. Jiwon M. Lee, Jaewon Shin, Sol Kim, Heon Yung Gee, Joon Suk Lee, Do Hyeon Cha, John Hoon Rim, Se-Jin Park, Ji Hong Kim, Ahmet Uçar, Andreas Kronbichler, Keum Hwa Lee, Jae Il Shin, "Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neuroendocrine Tumors (ROHHADNET) Syndrome: A Systematic Review", BioMed Research International, vol. 2018, Article ID 1250721, 17 pages, 2018.

2. 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 Jan 29;14:319-326. doi: 10.2147/IJGM.S293377. PMID: 33542648; PMCID: PMC7853626

3.Zelko FA, Welbel RZ, Rand CM, Stewart T, Fadl-Alla A, Khaytin I, Slattery SM, Weese-Mayer DE. Neurocognition as a biomarker in the rare autonomic disorders of CCHS and ROHHAD. Clin Auton Res. 2022 Oct 27. doi: 10.1007/s10286-022-00901-1. Epub ahead of print. PMID: 36289132.

Palavras Chave

ROHHAD; ganglioneuroblastoma; hypoventilation; hypothalamic dysfunction

Fonte de Fomento (se houver)

Declaração de conflito de interesses de TODOS os autores

The authors declare no competing interests.

Área

Manifestações neurológicas das doenças sistêmicas