ROHHAD(NET) Syndrome: Systematic Review of the Clinical Timeline and Recommendations for Diagnosis and Prognosis

Abstract

Context Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation and neural crest tumor (ROHHHAD[NET]) is a rare and potentially fatal disease. No specific diagnostic biomarker is currently available, making prompt diagnosis challenging. Since its first definition in 2007, a complete clinical analysis leading to specific diagnosis and follow-up recommendations is still missing. Objective The purpose of this work is to describe the clinical timeline of symptoms of ROHHAD(NET) and propose recommendations for diagnosis and follow-up. Design We conducted a systematic review of all ROHHAD(NET) case studies and report a new ROHHAD patient with early diagnosis and multidisciplinary care. Methods All the articles that meet the definition of ROHHAD(NET) and provide chronological clinical data were reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis individual patient data guidelines. The data were grouped into 7 categories: hypothalamic dysfunction, autonomic dysregulation, hypoventilation, NET, psychiatric symptoms, other clinical manifestations, and outcome. Results Forty-three individual patient data descriptions were analyzed. The timeline of the disease shows rapid-onset obesity followed shortly by hypothalamic dysfunction. Dysautonomia was reported at a median age of 4.95 years and hypoventilation at 5.33 years, or 2.2 years after the initial obesity. A NET was reported in 56% of the patients, and 70% of these tumors were diagnosed within 2 years after initial weight gain. Conclusion Because early diagnosis improves the clinical management and the prognosis in ROHHAD(NET), this diagnosis should be considered for any child with rapid and early obesity. We propose guidance for systematic follow-up and advise multidisciplinary management with the aim of improving prognosis and life expectancy.

ROHHAD (Rapid-onset Obesity with Hypoventilation, Hypothalamic Dysfunction, Autonomic Dysregulation) Syndrome—What Every Pediatrician Should Know About the Etiopathogenesis, Diagnosis and Treatment: A Review

“…ROHHAD syndrome is a very rare disorder, about 100 cases being reported to date and it is considered a relatively new disease. 4 , 5 Because of the explosion of the exogenous obesity in children worldwide, ROHHAD syndrome must be considered for differential diagnosis in obese children.…”

“…Clinical presentation of these patients is variable in severity and timing. 2 , 4 , 5 The clinical presentation is heterogenous, there are cases with marked endocrine involvement, while others exhibit marked behavioral disturbances.…”

“…Dysnatremia (hypernatremia and hyponatremia) may be present and is linked with impaired water balancing such as polydipsia or diabetes insipidus. 4 , 5 , 30 , 31 , 34 These manifestations appear from months to years following the rapid-onset obesity.…”

“…Enlargement of the pituitary gland and generalized brain atrophy were also reported. 4 , 5 , 34 , 35 …”

ROHHAD Sendromlu Olgunun King’in Amaca Ulaşma Kuramına Dayalı Bakımının Planlanması

“…Bu nedenle evde etkili bir non-invaziv ventilasyon uygulaması ve uyku saatlerinin düzenli olması, hastanın yaşına göre normal hareketler sergilemesi için önemlidir. Medikal tedavide ise yüksek doz siklofosfamidin, vücut kütle indeksi ve nöropsikolojik fonksiyonlara pozitif etkisinin olduğu bildirilmiştir (Harvengt, 2020).…”