Agyria-pachygyria (lissencephaly syndrome)

Abstract

A clinico-pathological report is given on 4 cases of agyria (premature neonate to age 13 months), 3 cases of pachygyria (aged 2,5 to 4,3 years) and a boy aged 4,5 years with temporal pachygyria and frontal microgyrias. Clinical features, more pronounced in agyria than in pachygyria, were microcephaly, frequent facial anomalies, neonatal feeding difficulties, hypotonia with subsequent seizures, hypsarrhythmic EEG pattern in 3 children, arrest of psychomotor development and signs of decerebration. One case of agyria occurred with familial faciorenal dysplasia, two were associated with congenital heart disease, and the fourth with chromosomal abnormality. Morphologically, the colpocephalic brain showed a four-layered agyric pallium with radially aligned cell columns and periventricular heterotopias, lacking differentiation of the claustra, olivary heterotopias and cerebellar dysgenesias in the 4 younger infants. In the agyric neonate additional agenesis of corpus callosum was present. Pachygyric brains showed a six-layered cortex, periventricular heterotopias, lacking differentiation of the claustra, but no cerebello-olivary anomalies. Cytoarchitectonic analysis of the agyric cortex suggests a disorder of neuronal migration during stage III of neocortex formation (Rakic and Sidman) between the 11th and 13th fetal week, while the pachygyric cortex showing the later formed layers II and IV presumable is caused by an attenuated and later disorder acting in early stage IV of neocortex formation, i. e. around or after the 13th fetal week. Additional insula-claustrum dysplasia, olivary and cerebellar anomalies are due to concomittent migration disorders between the 11th and 14th week. Along this period there is a gradient from agyric to normal six-layered cortex, whereas microgyria presumably results from an event occurring after migration has terminated (after the 16th fetal week). Etiological factors of agyria-pachygyria may be both hereditary (familial lissencephaly-syndrome) and environmental ones (prenatal drug application or intrauterine perfusion disorders).