Early-onset ROHHAD-NET syndrome with severe sleep-related respiratory distress: A case report
Year: 2025
Type: article
Study design: Case Report
Abstract: Background Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is a rare pediatric disorder often associated with neuroendocrine tumors (ROHHAD-NET). Recent studies have identified serum anti-ZSCAN1 antibodies in most patients, suggesting an autoimmune paraneoplastic neurological syndrome. Respiratory complications, particularly sleep-related hypoventilation, contribute to high mortality rates. Although immunomodulatory therapies have been attempted, their efficacy is limited. Case presentation A 2-year-old girl presented with rapid weight gain, hypothalamic dysfunction, autonomic abnormalities, and severe sleep-related hypoventilation. The patient developed intermittent strabismus, hyperphagia, and behavioral changes over 4 months. Imaging revealed a retroperitoneal paravertebral mass, which was pathologically diagnosed as ganglioneuroma. Laboratory findings revealed central hypothyroidism, growth hormone deficiency, hyperprolactinemia, and markedly elevated serum anti-ZSCAN1 antibody levels. Following admission, the patient experienced apnea, airway obstruction, excessive secretions, and wheezing during sleep, requiring mechanical ventilation. Immunotherapies, including plasma exchange, high-dose intravenous immunoglobulin, methylprednisolone pulse, rituximab, mycophenolate mofetil, and intrathecal methotrexate, improve appetite, behavior, and neuropsychiatric symptoms. Cerebrospinal fluid oligoclonal bands were negative, indicating partial immunological remission; however, sleep-related hypoventilation persisted. After discharge, the patient experienced sudden respiratory arrest during sleep and died despite resuscitation. Conclusion This case highlights that, ROHHAD-NET, autonomic dysfunction may cause complex sleep-related respiratory failure beyond simple obstructive or central hypoventilation. Elevated anti-ZSCAN1 antibody titers may be correlated with earlier disease onset and severity. Early recognition, aggressive immunomodulation, and consideration of ventilatory support are essential to prevent sudden deaths. Anti-ZSCAN1 antibodies may serve as useful biomarkers for the diagnosis and treatment of ROHHAD-NETs.
Authors: Yudai Hirakawa, Masanori Nishi, Naoya Higuchi, Hiroi Eguchi, Takuji Nakamura, Yuya Ito, Takaharu Yamada, Masafumi Sanefuji, Akari Nakamura-Utsunomiya, Muneaki Matsuo
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $800
OpenAlex ID: W7108516905