engleski

POMT-1 associated Walker-Warburg syndrome: A disorder of dendritic development of neocortical neurons

We have analyzed the morphology and den- dritic development of neocortical neurons in a 2.5-month-old infant with Walker-Warburg syndrome homozygotic for a novel POMT1 gene mutation, by Golgi methods. We found that pyramidal neurons frequently displayed abnormal (oblique, horizontal, or inverted) ori- entation. A novel fi nding of this study is that members of the same population of pyramidal neurons display diff erent stages of development of their dendritic arborizations: some neurons had poorly developed dendrites and thus resem- bled pyramidal neurons of the late fetal cortex ; for some neurons, the level of diff erentiation cor- responded to that in the newborn cortex ; fi nally, some neurons had quite elaborate dendritic trees as expected for the cortex of 2.5-month- old infant. In addition, apical dendrites of many pyramidal neurons were conspiciously bent to one side, irrespective to the general orientation of the pyramidal neuron. These fi ndings suggest that Walker-Warburg lissencephaly is charac- terized by two hitherto unnoticed pathogenetic changes in the cerebral cortex: (a) heterochronic decoupling of dendritic maturation within the same neuronal population (with some members signifi cantly lagging behind the normal matura- tional schedule) and (b) anisotropically distorted shaping of dendritic trees, probably caused by patchy displacement of molecular guidance cues for dendrites in the malformed cortex.

Cobblestone lissencephaly; MRI

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