Rituximab Brings Only Transient Relief in Children With ROHHAD Syndrome

A rare and devastating pediatric disorder has been documented in new detail by Chinese researchers, who report that three children in their series who received an immunotherapy drug experienced only fleeting benefits before the disease resumed its relentless course. The condition, known as ROHHAD syndrome, takes its name from its core features: Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation. In a retrospective case series published in the journal Frontiers in Pediatrics, a team from Peking University First Hospital and Beijing Children’s Hospital Capital Medical University reviewed the medical records of seven children diagnosed with ROHHAD syndrome between 2010 and 2025, aiming to map how the disorder unfolds in Chinese children and to evaluate how rituximab performs in real-world clinical practice.

The seven patients included three males and four females. Their symptoms first appeared at a median age of 2.8 years, with individual onset ages ranging from 2.0 to 7.9 years. Diagnosis came considerably later, at a median age of 3.8 years, and the median delay between onset and diagnosis was 1.2 years, stretching from half a year to 3.6 years in the slowest-recognized case. Every child in the series displayed the full triad that defines the syndrome. Rapid weight gain emerged at a median age of 3.2 years, hypothalamic dysfunction at 3.1 years, and autonomic dysregulation at 3.4 years, indicating that the three hallmark components tend to arrive in close succession during early childhood.

One of the most striking findings concerned the brain and behavior. Neuropsychiatric abnormalities were universal, present in all seven children, and they emerged concurrently with or shortly after the rapid weight gain rather than as a late complication. The authors argue that this temporal pattern, which they describe as neuropsychiatric abnormalities occurring in parallel with or closely following rapid-onset obesity, may offer clinicians an early warning sign. In their conclusion, they emphasize that unexplained obesity combined with neuropsychiatric abnormalities in young children should raise high suspicion for ROHHAD syndrome, a disorder that is easily mistaken for ordinary childhood weight gain in its earliest phase.

Breathing and heart problems were frequent and severe in the cohort. Central hypoventilation, in which the brain fails to send adequate signals to keep breathing going, was documented in five of the seven patients, or 71.4 percent. Neural crest-derived tumors, a recognized companion of ROHHAD syndrome because the neural crest gives rise to certain tumor types, were found in four patients, also 57.1 percent. Cardiac involvement was present in four children, and in three of them the heart failure was severe, with an ejection fraction of just 31 percent, a measure of how much blood the heart pumps with each beat that falls far below normal values.

Neurological abnormalities were likewise present in every patient, with two children experiencing epileptic seizures. The inflammatory marker interleukin-6, a signaling molecule that rises during immune activation, was tested in four patients and found to be elevated in two. The authors note that the clinical picture was highly heterogeneous, with different children showing different combinations and severities of symptoms, which they say complicates both recognition and management of the syndrome.

Treatment outcomes formed the second major focus of the study. Six of the seven children received first-line immunotherapy consisting of corticosteroids or intravenous immunoglobulin, and the response was poor across the board. Three patients went on to receive rituximab, a monoclonal antibody that depletes B cells and is used in a range of autoimmune and inflammatory diseases. In all three rituximab-treated children, the researchers observed transient initial improvement, but the benefit did not last. Ultimately, all three experienced relentless disease progression, and one of the patients died.

The overall prognosis in the series was poor. One child died, one was left in a vegetative state, and the remaining five continued to show progressive disease. The authors conclude that clinical responses to rituximab were variable and transient, with no sustained long-term improvement observed in any of the treated patients. However, they are careful to qualify this finding: because the sample size was small and the treatment protocols were heterogeneous, differing between patients, no definitive conclusion regarding rituximab efficacy can be drawn from these data. The study is descriptive rather than comparative, and it cannot establish what the outcome would have been without the drug.

Despite these limitations, the case series carries practical weight for pediatricians. The authors underscore the need for routine multidisciplinary monitoring of children with ROHHAD syndrome, given the involvement of the hypothalamus, breathing control, the autonomic nervous system, the heart, and tumor surveillance within a single patient. Their central message is that the combination of rapid-onset obesity and neuropsychiatric abnormalities in a young child should prompt clinicians to consider this rare syndrome early, because the diagnostic delay in their cohort stretched up to 3.6 years and the disease can progress to severe heart failure and life-threatening hypoventilation before its nature becomes clear. As a retrospective review of seven children treated over fifteen years at two major Beijing hospitals, the study offers one of the more detailed portraits of ROHHAD syndrome in a Chinese pediatric population, while leaving open the question of whether any immunotherapy, including rituximab, can alter the long-term trajectory of this disorder.

Subject of Research: Clinical features of ROHHAD syndrome and rituximab treatment outcomes in a descriptive case series of Chinese children

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

Article References: Song, D., Chang, X., Zhang, Y., Wu, Y., Zhang, W., Li, J., & Ji, T. (2026). Clinical features of ROHHAD syndrome and treatment outcomes following rituximab therapy: a descriptive case series of Chinese children. Frontiers in Pediatrics, 14, Article 1960692. https://doi.org/10.3389/fped.2026.1960692

Image Credits: AI Generated

DOI: 10.3389/fped.2026.1960692

Keywords: Clinical, features, ROHHAD, syndrome, treatment, outcomes, following, rituximab, therapy, descriptive, case, series