Background: ROHHADNET syndrome affects children with normal development until 24 years. A paraneoplastic/autoimmune etiology has been suggested because of the association with neural crest tumours.
Objective and hypotheses: Aim of this study was to describe the phenotype of ROHHADNET patients, and 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 yet.
Method: Seven patients with ROHHADNET underwent clinical and instrumental studies; serum levels of several antibodies against neural receptors were assessed in six patients. CSF was tested for oligoclonal bands in 6/7 patients.
Results: All patients had uneventful history until 24 years, when they developed rapid weight gain, hyperprolactinemia, water/salt balance disruption and behavioral problems or EEG alterations (five patients). Central apneas were diagnosed in six patients and non-invasive ventilation was started in five patients (one patient borderline apneas). Central adrenal insufficiency was found in four patients (partial or total); all patients had GH deficiency, two patients had central precocious puberty, six patients had central hypothyroidism (one transient). Brain MRI was not significant in all patients. A retroperitoneal mass was found in four patients, and biopsy led to ganglioneuroma diagnosis in three of them. Serum neural receptors autoantibodies were undetectable in all tested patients. CSF and serum tested positive for oligoclonal bands in 3/6 patients.
Conclusion: We aimed to evaluate whether markers of autoimmune encephalitis could be detected in serum of patients with ROHHADNET, whose possible autoimmune etiology has been suggested based on the association with neural crest tumors and a partial response to intravenous immunoglobulin, or immunosuppressants. The results of our study were negative, but CSF tests have shown autoimmune activation in three patients so far. Further studies are ongoing in order to better evaluate the autoimmune status of these patients.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology