Brain pathology in the Meckel syndrome: a study of 59 cases

The Meckel syndrome (MS), relatively frequent in Finland, has been subjected to a nationwide study regarding the spectrum of anomalies, diagnostic criteria and epidemiology. This report describes the observations made on brain pathology in the 59 cases in the series. 10 cases were studied neuropathologically after formalin fixation of the brain. A spectrum of CNS malformations was seen with craniorachischisis totalis at the most severe end and a partial defect of corpus callosum as the only abnormality at the mildest end of the malformative spectrum. The most consistent malformation was occipital meningo-encephalocele, observed in 90% of the cases. Absence of olfactory bulbs was almost as frequent, while only two cases with a telencephalic holosphere were observed. Defects in midline commissuration (including absent or incomplete corpus callosum), associated with absence of the lateral ventricles, represented the third group of malformations common in MS. Polymicrogyria, heterotopias and characteristic, neuroepithelial rosettes were frequent microscopic features. Brain pathology in the Meckel syndrome thus displays a wide malformative spectrum with disturbances in both dorsal and ventral induction as well as in proliferation and migration. These findings suggest a heterochronic pathogenesis compatible with the genetic nature of this syndrome.