The pathogenesis of rohhad
Team leader: Dr. Lidia Sabater PhD
Overview
ROHHAD is a rare and complex syndrome characterized by rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation. Its clinical presentation often overlaps with genetic or metabolic disorders, making diagnosis and treatment particularly challenging.
Recent discoveries have linked ROHHAD syndrome with autoantibodies against ZSCAN1, particularly in children with an underlying neuroendocrine tumor. Our research builds on this finding by demonstrating that ZSCAN1 antibodies can also be present in patients with ROHHAD who do not have detectable tumors — expanding the clinical spectrum of the syndrome. ROHHAD mirrors other neuroimmune syndromes with suspected autoimmune origin—such as opsoclonus-myoclonus syndrome (OMS) in which half of the patients present with an associated tumor—even though no specific autoantibodies have yet been identified in OMS cases yet.
Our findings also include the first adult case of ROHHAD with ZSCAN1 antibodies, raising awareness that the syndrome may occur beyond childhood and could be underdiagnosed in adults with unexplained hypothalamic dysfunction, obesity, and hypoventilation.
Team leader: Dr. Thais Armangue MD, PhD
Together, our work supports the growing evidence for an immune-mediated pathogenesis of ROHHAD syndrome and highlights the potential for early diagnosis and immunotherapy, even in the absence of a tumor.
By studying serum and cerebrospinal fluid (CSF) samples, our goal is to identify potential biomarkers that could shed light on novel autoimmune mechanisms underlying ROHHAD and to expand the clinical profile.