Lissencephaly, Genetics of


The term lissencephaly (literally ‘smooth brain’) covers rare malformations which have in common a reduction of the cortical gyration and an abnormal cortical layering. Different forms of lissencephalies have been described: classical lissencephalies (also called type I) and its variants, and cobblestone lissencephalies (also called type II). Classical lissencephalies include lissencephalies with abnormalities in genes LIS1, DCX or ARX, isolated lissencephalies without any identified genetic defect, lissencephalies with severe microcephaly (microlissencephaly), and lissencephalies associated with syndromes of multiple malformations. The cobblestone lissencephaly is observed in three related syndromes: Walker–Warburg, Fukuyama and muscle‐eye‐brain (MEB) syndromes.

Keywords: neuronal migration; nucleokinesis; LIS1; DCX

Figure 1.

Classical lissencephaly (LIS1 gene mutation). (a) Axial brain section showing agyry‐pachygyry with anterior–posterior gradient (anterior being more severe) and the classical figure‐eight appearance of shallow sylvian fissures. (b) Coronal brain section showing the preserved cerebellum.

Figure 2.

Cobblestone lissencephaly. (a) Axial brain section showing pachygyry and polymicrogyry with anterior–posterior gradient, and hydrocephalus. (b) Sagittal brain section showing brain stem and cerebellar hypoplasia.



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Further Reading

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Passemard, Sandrine, Challard, François, Verloes, Alain, and Gressens, Pierre(Sep 2007) Lissencephaly, Genetics of. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020224]