ESPE Abstracts (2014) 82 P-D-1-2-33

Immunological Studies in Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, Autonomic Dysregulation, and Neural Tumor (ROHHADNET) Syndrome

Flavia Napolia, Annalisa Calcagnoa, Natascia di Lorgia, Anna Elsa Maria Allegria, Marianna Vannatia, Laura de Miglioa, Roberta Biancherib, Isabella Ceccherinic, Yael Hacohend, Leslie Jacobsond, Angela Vincentd & Mohamad Maghniea

aDepartment of Pediatrics, Istituto G. Gaslini, Genova, Italy; bDepartment of Neuroscience, Isituto G. Gaslini, Genova, Italy; cLaboratorio di Genetica Molecolare, Istituto G. Gaslini, Genova, Italy; dNuffield Department of Clinical Neurosciences, Oxford, UK

Background: ROHHADNET syndrome affects children with normal development until 2–4 years of age.

Objective and hypotheses: Aim of this study was to evaluate a possible role of autoimmunity in this disorder. In spite of a suspicion for genetic etiology, disease-associated genetic variations have not been identified. A paraneoplastic/autoimmune etiology has been suggested mainly because of the association with neural crest tumors.

Method: Six patients with ROHHADNET underwent clinical and neuroradiologic studies; serum levels of several antibodies against neural receptors (NMDAR, LGI1, CASPR2, dopamine receptor, AMPAR, ganglionic AChR, VGKC, and VGCC) were assessed. CSF was tested for oligoclonal bands in 2/6 patients.

Results: All patients had uneventful history until 2–4 years, when they developed rapid weight gain, hyperprolactinemia, water/salt balance disruption and behavioral problems or EEG alterations (five patients). Central apnoeas were diagnosed in four patients and non-invasive ventilation was started. Central adrenal insufficiency was found in three patients; all patients had GH deficiency, two patients had central precocious puberty, five patients had central hypothyroidism. Brain MRI was normal or not significant in all patients. A retroperitoneal mass was found in four patients. The above mentioned serum autoantibodies were undetectable in all patients. CSF tested positive for oligoclonal bands in patient.

Conclusion: In this study we aimed to evaluate whether the autoantibodies responsible for immune mediated encephalitis could be detected in serum of patients with ROHHADNET, whose possible autoimmune etiology has been suggested based on the frequent association with neural crest tumors, the finding of extensive infiltrates of lymphocytes and histiocytes in the hypothalamus of some patients and a partial response to intravenous immunoglobulin, or immunosuppressants. The results of our study were negative, but CSF tests have shown autoimmune activation in one patient so far. Additional studies are ongoing to further evaluate the autoimmune status of these patients.