« Lissencephaly » (Ly) includes a group of malformations sharing the common feature of attenuation or absence of cerebral cortical folding associated with abnormal organization of the cortical layers, all as a result of abnormal neuronal migration during embryogenesis. Infants with Ly have feeding and swallowing difficulties, early muscle hypotonia followed by limb hypertonia, seizures, especially infantile spasms and severe psychomotor retardation. The precise prevalence is unknown.
There are multiple forms of Ly; their classification is based on associated malformations and underlying aetiology.
Two large groups can be distinguished: classical Ly, or type I and its variants and cobblestone Ly, or type II. In classical Ly the cortex appears thickened with four or more disorganized layers instead of six normal ones. Type I variants adduce extra-cortical abnormalities including total or subtotal agenesis of the corpus callosum and/or cerebellar hypoplasia. Classical Lys and its variant forms can be further divided into subgroups. Three are distinguished on the basis of genetic association - abnormalities in the LISI gene (isolated Ly and Miller-Dieker syndrome); abnormalities of the TUBA3 and DCX genes; and mutations in the ARX gene (XLAG syndrome or X-linked Ly with agenesis of the corpus callosum). The incidence of Type I Ly is around 1 in 100,000 births. Additionally isolated Ly without a known genetic defect, Ly with severe microcephaly, and Ly associated with multiple malformations are recognised syndromes and included in this group.
Type II Ly is found in the Walker-Warburg, Fukuyama, and MEB (Muscle-Eye- Brain) syndromes. There is global disorganization of cerebral organogenesis with an uneven cortical surface that is pebbled or cobblestone in appearance. Microscopic examination shows total cortical disorganization and an absence of distinguishable cortical layers. The management is symptomatic: Swallowing difficulties require adapted feeding, respiratory and articular physiotherapy to prevent hypotonia related abnormalities and gastro-oesophageal reflux. The associated epilepsy is often resistant to treatment.
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