Antibodies Against ZSCAN1 in Pediatric and Adult Patients With Non-Paraneoplastic ROHHAD Syndrome

Abstract

Objectives: To report the association of zinc finger and SCAN domain containing 1 antibodies (ZSCAN1-abs) with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome in patients without tumor.

Methods: Patients with symptoms compatible with ROHHAD syndrome but without an associated tumor were selected from our database. Serum and CSF samples were examined for the presence of ZSCAN1-abs by an in-house cell-based assay. In addition, samples from 149 patients with several inflammatory and noninflammatory disorders and 50 healthy participants served as controls.

Results: Thirteen patients with ROHHAD syndrome were identified. Of these, we had paired serum/CSF samples from 6 patients and only serum from the other 7. Five of 6 patients (83.3%) with paired serum/CSF (4 children, 1 adult) had ZSCAN-abs only in CSF and 1 had antibodies in serum and CSF. ZSCAN1-abs were not detected in the remaining 7 patients with ROHHAD with only serum available or in any of the 199 control samples.

Discussion: Patients with ROHHAD syndrome should be investigated for the presence of ZSCAN1-abs in CSF. The antibodies do not necessarily predict the presence of a tumor. The detection of ZSCAN1-abs in an adult patient suggests that this condition also occurs beyond the pediatric age.

Figure. Cell-Based Assay of HEK293 Cells Expressing Human ZSCAN1

(A) Incubation of the cells with CSF (diluted 1:5) of patient 2 shows intense reactivity (green fluorescence) with ZSCAN1 protein. (B) Incubation of the same cells with a commercial polyclonal ZSCAN1 antibody shows specific reactivity (red fluorescence) with ZSCAN1. The colocalization of both reactivities is shown in panel C. Panels D–F show similar studies with CSF from a control subject that has no ZSCAN1-abs (e.g., absence of reactivity in D). For all panels, the nuclei are stained with 4′,6-diamidino-2-phenylindole (DAPI; blue fluorescence). Arrows point areas of immunoreactivity. Scale bar = 10 µm.