gms | German Medical Science

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.