To expand the known phenotypic spectrum of paraneoplastic ROHHAD-NET (rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation - associated with neuroendocrine tumors).
ROHHAD-NET is a rare and incompletely characterized paraneoplastic disease, typically presenting in young pre-pubertal children with rapid weight gain followed by sleep disordered breathing, and eventually life threatening hypothalamic/autonomic failure. We present a highly atypical case of ROHHAD-NET in a teenager which did not follow this expected trajectory.
We performed a retrospective descriptive chart review of a single case.
A 13 year old girl with idiopathic growth hormone deficiency presented with unexplained hypothermia. She developed sudden confusion and tremulousness at school without provoking cause, and was found to be extremely cold to touch. Initial vitals confirmed profound hypothermia (temp 32 C) and associated bradycardia (HR 30-50) requiring passive external warming in the intensive care unit. Extensive workup included negative toxicology screening, normal endocrine/hormonal labs, normal brain and spine MRI, negative serum/CSF autoimmune antibodies (including autonomic ganglionopathy panel), and non-diagnostic comprehensive exome sequencing. Hypothermia improved with initiation of alpha agonist and she was discharged. Over the next several months she weaned off the alpha agonist, but developed progressive weight gain with BMI increase from 28.86 kg/m2 to 38.63 kg/m2 (12 month span). Full body MRI revealed a thoracic paraspinal mass, which was resected and confirmed to be ganglioneuroma. Polysomnography showed severe obstructive sleep apnea, without central apnea/hypoventilation. Re-analysis of genetic testing for PHOX2B pathogenic variants/repeats was negative. She was clinically diagnosed with ROHHAD-NET, and initiated immune therapy with intravenous immunoglobulin (1 g/kg monthly). Following tumor resection and IVIG initiation her BMI improved (34.88 kg/m2 after 6 months of treatment) and she has had no further autonomic instability.
ROHHAD-NET is not exclusive to young children, and autonomic/hypothalamic failure may precede the onset of rapid weight gain.