Lissencephaly, Genetics of

Sandrine Passemard, Inserm, U676, Hôpital Robert Debré, Paris, France
François Challard, APHP, Hôpital Robert Debré, Service d'Imagerie Médicale, Paris, France
Alain Verloes, APHP, Hôpital Robert Debré, Departement de Génétique, Paris, France
Pierre Gressens, Inserm, U676, Hôpital Robert Debré, Paris, France

Published online: September 2007

DOI: 10.1002/9780470015902.a0020224

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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 References
    Allias F, Buenerd A, Bouvier R et al. (2004) The spectrum of type III lissencephaly: a clinicopathological update. Fetal and Pediatric Pathology 23(5–6): 305–317.
    Barkovich AJ, Kuzniecky RI and Dobyns WB (2001) Radiologic classification of malformations of cortical development. Current Opinion in Neurology 14(2): 145–149.
    Barkovich AJ, Kuzniecky RI, Jackson GD et al. (2005) A developmental and genetic classification for malformations of cortical development. Neurology 65(12): 1873–1887.
    Beltran-Valero de Bernabe D, Currier S, Steinbrecher A et al. (2002) Mutations in the O-mannosyltransferase gene POMT1 give rise to the severe neuronal migration disorder Walker–Warburg syndrome. American Journal of Human Genetics 71(5): 1033–1043.
    Beltran-Valero de Bernabe D, Voit T, Longman T et al. (2004) Mutations in the FKRP gene can cause muscle-eye-brain disease and Walker–Warburg syndrome. Journal of Medical Genetics 41(5): e61.
    Berry-Kravis E and Israel J (1994) X-linked pachygyria and agenesis of the corpus callosum: evidence for an X chromosome lissencephaly locus. Annals of Neurology 36(2): 229–233.
    Caspi M, Atlas R, Kantor A et al. (2000) Interaction between LIS1 and doublecortin, two lissencephaly gene products. Human Molecular Genetics 9(15): 2205–2213.
    Chen Y, Beffert U, Ertunc M et al. (2005) Reelin modulates NMDA receptor activity in cortical neurons. Journal of Neuroscience 25(36): 8209–8216.
    des Portes V, Pinard JM, Billuart P et al. (1998) A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome. Cell 92(1): 51–61.
    Dobyns WB and Truwit CL (1995) Lissencephaly and other malformations of cortical development: 1995 update. Neuropediatrics 26(3): 132–147.
    Forster E, Jossin Y, Zhao S et al. (2006) Recent progress in understanding the role of Reelin in radial neuronal migration, with specific emphasis on the dentate gyrus. European Journal of Neurosciences 23(4): 901–909.
    Friocourt G, Kappeler C and Saillour Y (2005) Doublecortin interacts with the ubiquitin protease DFFRX, which associates with microtubules in neuronal processes. Molecular and Cellular Neurosciences 28(1): 153–164.
    Gdalyahu A, Ghosh I, Levy T et al. (2004) DCX, a new mediator of the JNK pathway. Embo Journal 23(4): 823–832.
    Kato M and Dobyns WB (2005) X-linked lissencephaly with abnormal genitalia as a tangential migration disorder causing intractable epilepsy: proposal for a new term “interneuronopathy”. Journal of Child Neurology 20(4): 392–397.
    Keays DA, Tian G, Poirier K et al. (2007) Mutations in alpha-tubulin cause abnormal neuronal migration in mice and lissencephaly in humans. Cell 128(1): 45–57.
    Kobayashi K, Nakahori Y, Miyake M et al. (1998) An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy. Nature 394(6691): 388–392.
    Kuwano A, Ledbetter SA, Dobyns WB et al. (1991) Detection of deletions and cryptic translocations in Miller–Dieker syndrome by in situ hybridization. American Journal of Human Genetics 49(4): 707–714.
    Li J, Lee WL and Cooper JA (2005) NudEL targets dynein to microtubule ends through LIS1. Nature Cell Biology 7(7): 686–690.
    Martin PT (2005) The dystroglycanopathies: the new disorders of O-linked glycosylation. Seminars in Pediatric Neurology 12(3): 152–158.
    Miyata H, Chute DJ, Fink J et al. (2004) Lissencephaly with agenesis of corpus callosum and rudimentary dysplastic cerebellum: a subtype of lissencephaly with cerebellar hypoplasia. Acta Neuropathologica (Berlin) 107(1): 69–81.
    Poirier K, Van Esch H, Friocourt G et al. (2004) Neuroanatomical distribution of ARX in brain and its localisation in GABAergic neurons. Brain Research Molecular Brain Research 122(1): 35–46.
    Reiner O, Carrozzo R, Shen Y et al. (1993) Isolation of a Miller–Dieker lissencephaly gene containing G protein beta-subunit-like repeats. Nature 364(6439): 717–721.
    Ross ME, Swanson K and Dobyns WB (2001) Lissencephaly with cerebellar hypoplasia (LCH): a heterogeneous group of cortical malformations. Neuropediatrics 32(5): 256–263.
    Sarnat HB and Flores-Sarnat L (2003) Etiological classification of CNS malformations: integration of molecular genetic and morphological criteria. Epileptic Disorder 5: S35–S43.
    Tsai JW, Chen Y, Kriegstein AR and Vallee RB (2005) LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages. Journal of Cell Biology 170(6): 935–945.
    van Reeuwijk J, Brunner HG and van Bokhoven H (2005) Glyc-O-genetics of Walker–Warburg syndrome. Clinical Genetics 67(4): 281–289.
    van Reeuwijk J, Maugenre S, van den Elzen C et al. (2006) The expanding phenotype of POMT1 mutations: from Walker–Warburg syndrome to congenital muscular dystrophy, microcephaly, and mental retardation. Human Mutation 27(5): 453–459.
    Yoshida A, Kobayashi K, Manya H et al. (2001) Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferase, POMGnT1. Developmental Cell 1(5): 717–724.
 Further Reading
    Clark GD (2004) The classification of cortical dysplasias through molecular genetics. Brain Development 26(6): 351–362.
    Francis F, Meyer G, Fallet-Bianco C et al. (2006) Human disorders of cortical development: from past to present. European Journal of Neurosciences 23(4): 877–893.
    Friocourt G, Poirier K, Rakic S et al. (2006) The role of ARX in cortical development. European Journal of Neurosciences 23(4): 869–876.
    Gleeson JG (2001) Neuronal migration disorders. Mental Retardation and Developmental Disabilities Research Review 7(3): 167–171.
    Gressens P (2006) Pathogenesis of migration disorders. Current Opinion in Neurology 19(2): 135–140.
    Guerrini R and Filippi T (2005) Neuronal migration disorders, genetics, and epileptogenesis. Journal of Child Neurology 20(4): 287–299.
    Kato M and Dobyns WB (2003) Lissencephaly and the molecular basis of neuronal migration. Human Molecular Genetics 12(1): R89–96.
    Leventer RJ (2005) Genotype-phenotype correlation in lissencephaly and subcortical band heterotopia: the key questions answered. Journal of Child Neurology 20(4): 307–312.
    Mochida GH and Walsh CA (2004) Genetic basis of developmental malformations of the cerebral cortex. Archives of Neurology 61(5): 637–640.
    Pilz D, Stoodley N and Golden JA (2002) Neuronal migration, cerebral cortical development, and cerebral cortical anomalies. Journal of Neuropathology and Experimental Neurology 61(1): 1–11.

Related Sub-Topics:

Neurobiology of Disease | Organisation of the Nervous System | Neurons | Nervous System Development | Development of Vertebrate Nervous System | Molecular Genetics of Common and Complex Disease | Specific Genetic Disorders
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Article Title: Lissencephaly, Genetics of
 
How to Cite close
Passemard, Sandrine, Challard, François, Verloes, Alain, and Gressens, Pierre(Sep 2007) Lissencephaly, Genetics of. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020224]