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Neonatology pp 1131-1136 | Cite as

Malformations of Cortical Development: Genetic Aspects

  • Renzo Guerrini
  • Elena Parrini

Abstract

The development of the human cerebral cortex is a complex dynamic process that occurs during several gestational weeks [1]. During the first stage, stem cells proliferate and differentiate into young neurons or glial cells deep in the forebrain in the ventricular and subventricular zones lining the cerebral cavity. During the second stage, cortical neurons migrate away from their place of origin: most cells migrate along the radial glial fibres from the periventricular region towards the pial surface, where each successive generation passes one another and settles in an inside-out pattern within the cortical plate. When neurons reach their destination, they stop migrating and order themselves into specific ”architectonic“ patterns guiding cells to the correct location in the cerebral cortex. This third phase involves final organization within the typical six layers of cortex, associated with synaptogenesis and apoptosis.

Keywords

Infantile Spasm Congenital Muscular Dystrophy Germline Mosaicism Periventricular Nodular Heterotopia Spastic Quadriplegia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Gleeson JG, Walsh CA (2000) Neuronal migration disorders: from genetic diseases to developmental mechanisms. Trends Neurosci 23: 352–359PubMedCrossRefGoogle Scholar
  2. 2.
    Guerrini R, Dobyns W, Barkovich A (2008) Abnormal development of the human cerebral cortex: genetics, functional consequences and treatment options. Trends Neurosci 31: 154–162PubMedCrossRefGoogle Scholar
  3. 3.
    Barkovich AJ, Kuzniecky RI, Jackson GD et al (2005) A developmental and genetic classification for malformations of cortical development. Neurology 65: 1873–1887PubMedCrossRefGoogle Scholar
  4. 4.
    Guerrini R, Parrini E (2010) Neuronal migration disorders. Neurobiol Dis 38: 154–66PubMedCrossRefGoogle Scholar
  5. 5.
    Cardoso C, Leventer RJ, Dowling JJ et al (2002) Clinical and molecular basis of classical lissencephaly: Mutations in the LIS1 gene (PAFAH1B1). Hum Mutat 19: 4–15PubMedCrossRefGoogle Scholar
  6. 6.
    Matsumoto N, Leventer RJ, Kuc JA et al (2001) Mutation analysis of the DCX gene and genotype/phenotype correlation in subcortical band heterotopia. Eur J Hum Genet 9: 5–12PubMedCrossRefGoogle Scholar
  7. 7.
    Mei D, Lewis R, Parrini E et al (2008) High frequency of genomic deletions and duplication in the LIS1 gene in lissencephaly: implications for molecular diagnosis. J Med Genet 45: 355–361PubMedCrossRefGoogle Scholar
  8. 8.
    Gleeson JG, Minnerath S, Kuzniecky RI et al (2000) Somatic and germline mosaic mutations in the doublecortin gene are associated with variable phenotypes. Am J Hum Genet 67: 574–581PubMedCrossRefGoogle Scholar
  9. 9.
    Guerrini R, Moro F, Andermann E et al (2003) Nonsyndromic mental retardation and cryptogenic epilepsy in women with doublecortin gene mutations. Ann Neurol 54: 30–37PubMedCrossRefGoogle Scholar
  10. 10.
    Parrini E, Ramazzotti A, Dobyns WB et al (2006) Periventricular heterotopia: phenotypic heterogeneity and correlation with Filamin A mutations. Brain 129: 1892–1906PubMedCrossRefGoogle Scholar
  11. 11.
    Guerrini R, Mei D, Sisodiya S et al (2004) Germline and mosaic mutations of FLN1 in men with periventricular heterotopia. Neurology 63: 51–56PubMedGoogle Scholar
  12. 12.
    Sheen VL, Ganesh VS, Topcu M et al (2004) Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex. Nat Genet 36: 69–76PubMedCrossRefGoogle Scholar
  13. 13.
    Roll P, Rudolf G, Pereira S et al (2006) SRPX2 mutations in disorders of language cortex and cognition. Hum Mol Genet 15:1195– 1207Google Scholar
  14. 14.
    Piao X, Hill RS, Bodell A et al (2004) G protein-coupled receptordependent development of human frontal cortex. Science 303: 2033–2036PubMedCrossRefGoogle Scholar
  15. 15.
    Jaglin XH, Poirier K, Saillour Y et al (2009) Mutations in the betatubulin gene TUBB2B result in asymmetrical polymicrogyria. Nat Genet 41: 746–752PubMedCrossRefGoogle Scholar
  16. 16.
    Dobyns WB, Mirzaa G, Christian SL et al (2008) Consistent chromosome abnormalities identify novel polymicrogyria loci in 1p36.3, 2p16.1-p23.1, 4q21.21-q22.1, 6q26-q27, and 21q2. Am J Med Genet A 146A: 1637–1654Google Scholar

Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  • Renzo Guerrini
    • 1
  • Elena Parrini
  1. 1.Pediatric Neurology Unit and LaboratoriesA. Meyer Children’s HospitalFlorenceItaly

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