Clinical features of ROHHAD syndrome and treatment outcomes following rituximab therapy: a descriptive case series of Chinese children

Objective We aimed to delineate the clinical phenotypes and symptom evolution of Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) syndrome in Chinese children and to evaluate the real-world efficacy of rituximab therapy. Methods We retrospectively reviewed the medical records of seven children diagnosed with ROHHAD syndrome between 2010 and 2025. Clinical data on baseline characteristics, core symptoms, tumor status, and therapeutic responses were extracted and analyzed using descriptive statistics. Results Among the 7 patients, there were 3 males and 4 females. The median age of onset was 2.8 years (2.0–7.9 years), and the median age at diagnosis was 3.8 years (3.5–8.5 years). The median diagnostic delay was 1.2 years (range, 0.5–3.6 years). All patients exhibited the triad of rapid-onset obesity, hypothalamic dysfunction, and autonomic dysregulation. The median ages of onset for obesity, hypothalamic dysfunction, and autonomic dysregulation were 3.2, 3.1, and 3.4 years, respectively. Neuropsychiatric abnormalities were universal (7/7, 100%), emerging concurrently with or shortly after weight gain. Central hypoventilation was observed in 5 patients (71.4%). Neural crest-derived tumors were found in 4 patients (57.1%). Cardiac involvement was present in 4 patients (57.1%), with 3 cases developing severe heart failure. All patients had neurological abnormalities, with 2 cases accompanied by epileptic seizures. Interleukin-6 (IL-6) levels were tested in 4 patients, with elevation in 2 cases. Six patients received first-line immunotherapy (corticosteroids/intravenous immunoglobulin) with poor response. Three patients received rituximab; all showed transient initial improvement but ultimately experienced relentless disease progression, and one patient died. The overall prognosis was poor: one death, one vegetative state, and progressive disease in the remaining 5 patients. Conclusion ROHHAD syndrome presents with highly heterogeneous clinical manifestations. Neuropsychiatric abnormalities may occur in parallel with or closely following rapid-onset obesity. Unexplained obesity and neuropsychiatric abnormalities in young children should raise high suspicion for this syndrome. Such patients warrant routine multidisciplinary monitoring. In the three patients who received rituximab, clinical responses were variable and transient, with no sustained long-term improvement observed. However, due to the small sample size and heterogeneous treatment protocols, no definitive conclusion regarding rituximab efficacy can be drawn.