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

Abstract

Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, autonomic dysregulation (ROHHAD) syndrome is a rare disease with unknown and debated etiology, characterized by precipitous obesity in young children, hypoventilation and autonomic dysregulation with various endocrine abnormalities. Neuroendocrine tumors can be associated in more than half of the cases. This rare condition has a severe outcome because of high morbidity and mortality. We provide a comprehensive description of the etiopathogenetic theories of the disease, clinical presentation, diagnostic workup and treatment possibilities.

Identification of clinical factors related to antibody‐mediated immune response to the subfornical organ

“…ROHHAD syndrome is characterized by early and rapid-onset of obesity accompanied with hypoventilation, autonomic dysregulation, and endocrine abnormalities, 20 whereas ROHHAD/NET syndrome also includes the presence of tumors of neural crest origin. 20 In some SFO-immunopositive patients also harbors tumors, suggesting some common paraneoplastic mecha- ZNF83, and KMT2B. 20 However, no report to date has described common gene variants or specific candidate genes underlying the pathology in these patients.…”

“…20 In some SFO-immunopositive patients also harbors tumors, suggesting some common paraneoplastic mecha- ZNF83, and KMT2B. 20 However, no report to date has described common gene variants or specific candidate genes underlying the pathology in these patients. An autoimmune mechanism has been considered based on autopsy findings of hypothalamic inflammation and the presence of oligoclonal bands in the cerebrospinal fluid.…”

“…We detected positive immunoreactivity to the mouse SFO in some patients who were previously diagnosed with ROHHAD or ROHHAD/NET syndrome. ROHHAD syndrome is characterized by early and rapid‐onset of obesity accompanied with hypoventilation, autonomic dysregulation, and endocrine abnormalities, 20 whereas ROHHAD/NET syndrome also includes the presence of tumors of neural crest origin 20 . In some SFO‐immunopositive patients also harbors tumors, suggesting some common paraneoplastic mechanisms with the ROHHAD/NET syndrome.…”

“…In some SFO‐immunopositive patients also harbors tumors, suggesting some common paraneoplastic mechanisms with the ROHHAD/NET syndrome. A recent report suggested that some patients with ROHHAD/NET syndrome harbored rare variants of several genes including PIK3R3, SPTBN5, PCF11, SRMS, ZNF83 , and KMT2B 20 . However, no report to date has described common gene variants or specific candidate genes underlying the pathology in these patients.…”

The Genetics of Sleep Disorders in Children: A Narrative Review

“…The mortality rate is estimated at 50-60% due to hypoventilation, cardiopulmonary failure and cardiopulmonary arrest [81]. The similarities between ROHHAD and CCHS suggest a possible genetic involvement in the aetiology of the ROHHAD syndrome, although some studies ruled out the presence of mutations in several candidate genes [82,83]. Epigenetic mechanisms have been hypothesised in some reports on the discordant presentation of ROHHAD syndrome in monozygotic twins [84].…”