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57. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie (DGNN)

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie

12. - 15.09.2012, Erlangen

Banner: 57. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie

DNT-like malformation and further neuropathological findings in a patient with Robinow syndrome

Meeting Abstract

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  • presenting/speaker Bernd F.M. Romeike - Jena University Hospital, FSU, Institute of Pathology, Jena, Germany
  • Mahmoud Diab - Jena University Hospital, FSU, Department of Cardiothoracic Surgery, Jena, Germany
  • Iver Petersen - Jena University Hospital, FSU, Institute of Pathology, Jena, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Erlangen, 12.-15.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgnnPP3.17

doi: 10.3205/12dgnn061, urn:nbn:de:0183-12dgnn0611

Veröffentlicht: 11. September 2012

© 2012 Romeike et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen ( Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.



Introduction: Robinow syndrome includes characteristic facial features, orodental abnormalities, mesomelic shortening of the limbs, a/hypoplasia of phalanges, and hypoplastic genitalia. A dominant form is caused by heterozygous mutation in the WNT5A gene on chromosome 3p14.3 and a recessive form is caused by homozygous or compound heterozygous mutations in the ROR2 gene on chromosome 9q22.31. About 20 % suffer mental retardation. Here we demonstrate for the first time neuropathological findings including DNT-like malformations in the amygdala.

Case report: The 23 y/o male patient died with virus pneumonia and sepsis. The main neuropathological findings were attributed to the limbic system. The amygdala showed several microscopically small foci resembling classic simple form of dysembryoplastic neuroepithelial tumor with typical specific glioneuronal elements with floating neurons. Floating neurons expressed MAP-2, Neu-N, neurofilaments and Synaptophysin. Intermingled stellate astrocytes expressed GFAP. Less than 1% of nuclei expressed Ki-67. No p53 or IDH-1 expression was noted. The hippocampus was caudally elongated and malrotated. The fornix displayed an abnormal shape. The right cingulum showed a cortical band attached to the corpus callosum. The side ventricles had synechias in the ventral aspects and occasional microscopically small nodular heterotopias.

Discussion: No previous reports describing neuropathological findings of patients with Robinow syndrome were found. The described malformations were for the most part attributable to abnormalities of cell migration. This is compatible with disturbance of WNT5A and ROR2 function. Wnt5a is implicated in control of cell orientation, polarity, and directional movement. Expression of Wnt5a was detected in brain tissue by Northern blot analysis. In mice in-situ hybridization detected a complex spatial and temporal pattern of Wnt5a expression. Furthermore, WNT5A and ROR2 interact. These findings suggest that the described malformation might well be related to disturbed WNT5A / ROR2 pathway. The role of the DNT-like malformation of the amygdala still needs to be established. Interestingly, despite only scarcely published genetic findings concerning DNTs two cases are described with isolated 9q loss.