Experimental Brain Research

, Volume 173, Issue 2, pp 322–333 | Cite as

Genetic malformations of cortical development

  • Renzo GuerriniEmail author
  • Carla Marini
Research Article


The malformations of the cerebral cortex represent a major cause of developmental disabilities, severe epilepsy and reproductive disadvantage. The advent of high-resolution MRI techniques has facilitated the in vivo identification of a large group of cortical malformation phenotypes. Several malformation syndromes caused by abnormal cortical development have been recognised and specific causative gene defects have been identified. Periventricular nodular heterotopia (PNH) is a malformation of neuronal migration in which a subset of neurons fails to migrate into the developing cerebral cortex. X-linked PNH is mainly seen in females and is often associated with focal epilepsy. FLNA mutations have been reported in all familial cases and in about 25% of sporadic patients. A rare recessive form of PNH due ARGEF2 gene mutations has also been reported in children with microcephaly, severe delay and early seizures. Lissencephaly-pachygyria and subcortical band heterotopia (SBH) are disorders of neuronal migration and represent a malformative spectrum resulting from mutations of either LIS1 or DCX genes. LIS1 mutations cause a more severe malformation in the posterior brain regions. Most children have severe developmental delay and infantile spasms, but milder phenotypes are on record, including posterior SBH owing to mosaic mutations of LIS1. DCX mutations usually cause anteriorly predominant lissencephaly in males and SBH in female patients. Mutations of DCX have also been found in male patients with anterior SBH and in female relatives with normal brain magnetic resonance imaging. Autosomal recessive lissencephaly with cerebellar hypoplasia, accompanied by severe delay, hypotonia, and seizures, has been associated with mutations of the reelin (RELN) gene. X-linked lissencephaly with corpus callosum agenesis and ambiguous genitalia in genotypic males is associated with mutations of the ARX gene. Affected boys have severe delay and seizures with suppression-burst EEG. Early death is frequent. Carrier female patients can have isolated corpus callosum agenesis. Among several syndromes featuring polymicrogyria, bilateral perisylvian polymicrogyria shows genetic heterogeneity, including linkage to chromosome Xq28 in some pedigrees, autosomal dominant or recessive inheritance in others, and an association with chromosome 22q11.2 deletion in some patients. About 65% of patients have severe epilepsy. Recessive bilateral frontoparietal polymicrogyria has been associated with mutations of the GPR56 gene. Epilepsy is often present in patients with cortical malformations and tends to be severe, although its incidence and type vary in different malformations. It is estimated that up to 40% of children with drug-resistant epilepsy have a cortical malformation. However, the physiopathological mechanisms relating cortical malformations to epilepsy remain elusive.


Cortical malformations Periventricular nodular heterotopia Lissencephaly Polymicrogyria Genetics Epilepsy 



This work was partly funded by a grant from the Italian Minister of Education (Dr. Carla Marini).


  1. Assadi AH, Zhang G, Beffert U, McNeil RS, Renfro AL, Niu S, Quattrocchi CC, Antalffy BA, Sheldon M, Armstrong DD, Wynshaw-Boris A, Herz J, D’Arcangelo G, Clark GD (2003) Interaction of reelin signaling and Lis1 in brain development. Nat Genet 35:270–276CrossRefPubMedGoogle Scholar
  2. Baker EM, Khorasgani MG, Gardner-Medwin D, Gholkar A, Griffiths PD (1996) Arthrogryposis multiplex congenita and bilateral parietal polymicrogyria in association with the intrauterine death of a twin. Neuropediatrics 27:54–56PubMedCrossRefGoogle Scholar
  3. Barkovich A (1995) Pediatric neuroimaging. Raven Press, New YorkGoogle Scholar
  4. Barkovich AJ, Kjos BO (1992) Nonlissencephalic cortical dysplasias: correlation of imaging findings with clinical deficits. AJNR Am J Neuroradiol 13:95–103PubMedGoogle Scholar
  5. Barkovich AJ, Guerrini R, Battaglia G, Kalifa G, N’Guyen T, Parmeggiani A, Santucci M, Giovanardi-Rossi P, Granata T, D’Incerti L (1994) Band heterotopia: correlation of outcome with magnetic resonance imaging parameters. Ann Neurol 36:609–617CrossRefPubMedGoogle Scholar
  6. Barkovich AJ, Kuzniecky RI, Jackson GD, Guerrini R, Dobyns WB (2001) Classification system for malformations of cortical development: update 2001. Neurology 57:2168–2178PubMedGoogle Scholar
  7. Barkovich AJ, Kuzniecky RI, Jackson GD, Guerrini R, Dobyns WB (2005) A developmental and genetic classification for malformations of cortical development. Neurology 65:1873–1887PubMedCrossRefGoogle Scholar
  8. Bingham PM, Lynch D, McDonald-McGinn D, Zackai E (1998) Polymicrogyria in chromosome 22 delection syndrome. Neurology 51:1500–1502PubMedGoogle Scholar
  9. Bix GJ, Clark GD (1998) Platelet-activating factor receptor stimulation disrupts neuronal migration in vitro. J Neurosci 18:307–318PubMedGoogle Scholar
  10. Bonneau D, Toutain A, Laquerriere A, Marret S, Saugier-Veber P, Barthez MA, Radi S, Biran-Mucignat V, Rodriguez D, Gelot A (2002) X-linked lissencephaly with absent corpus callosum and ambiguous genitalia (XLAG): clinical, magnetic resonance imaging, and neuropathological findings. Ann Neurol 51:340–349CrossRefPubMedGoogle Scholar
  11. Boycott KM, Flavelle S, Bureau A, Glass HC, Fujiwara TM, Wirrell E, Davey K, Chudley AE, Scott JN, McLeod DR, Parboosingh JS (2005) Homozygous deletion of the very low density lipoprotein receptor gene causes autosomal recessive cerebellar hypoplasia with cerebral gyral simplification. Am J Hum Genet 77:477–83CrossRefPubMedGoogle Scholar
  12. Brunelli S, Faiella A, Capra V, Nigro V, Simeone A, Cama A, Boncinelli E (1996) Germline mutations in the homeobox gene EMX2 in patients with severe schizencephaly. Nat Genet 12:94–96CrossRefPubMedGoogle Scholar
  13. Cardoso C, Leventer RJ, Matsumoto N, Kuc JA, Ramocki MB, Mewborn SK, Dudlicek LL, May LF, Mills PL, Das S, Pilz DT, Dobyns WB, Ledbetter DH (2000) The location and type of mutation predict malformation severity in isolated lissencephaly caused by abnormalities within the LIS1 gene. Hum Mol Genet 9:3019–3028CrossRefPubMedGoogle Scholar
  14. Carroll RC, Gerrard JM (1982) Phosphorylation of platelet actin-binding protein during platelet activation. Blood 59:466–71PubMedGoogle Scholar
  15. Chen M, Stracher A (1989) In situ phosphorylation of platelet actin-binding protein by cAMPdependent protein kinase stabilizes it against proteolysis by calpain. J Biol Chem 264:14282–9PubMedGoogle Scholar
  16. D’Arcangelo G (2006) Reelin mouse mutants as models of cortical development disorders. Epilepsy Behav 8:81–90CrossRefPubMedGoogle Scholar
  17. Dobyns WB, Reiner O, Carrozzo R, Ledbetter DH (1993) Lissencephaly. A human brain malformation associated with deletion of the LIS1 gene located at chromosome 17p13. JAMA 270:2838–2842CrossRefPubMedGoogle Scholar
  18. Dobyns WB, Guerrini R, Czapansky-Beilman DK, Pierpont ME, Breningstall G, Yock DH Jr, Bonanni P, Truwit CL (1997) Bilateral periventricular nodular heterotopia with mental retardation and syndactyly in boys: a new X-linked mental retardation syndrome. Neurology 49:1042–1047PubMedGoogle Scholar
  19. Dobyns WB, Berry-Kravis E, Havernick NJ, Holden KR, Viskochil D (1999a) X-linked lissencephaly with absent corpus callosum and ambiguous genitalia. Am J Med Genet 86:331–337CrossRefGoogle Scholar
  20. Dobyns WB, Truwit CL, Ross ME, Matsumoto N, Pilz DT, Ledbetter DH, Gleeson JG, Walsh CA, Barkovich AJ (1999b) Differences in the gyral pattern distinguish chromosome 17-linked and X-linked lissencephaly. Neurology 53:270–277Google Scholar
  21. Dubeau F, Tampieri D, Lee N, Andermann E, Carpenter S, Leblanc R, Olivier A, Radtke R, Villemure JG, Andermann F (1995) Periventricular and subcortical nodular heterotopia. A study of 33 patients. Brain 118:1273–1287PubMedCrossRefGoogle Scholar
  22. Eksioglu YZ, Scheffer IE, Cardenas P, Knoll J, DiMario F, Ramsby G, Berg M, Kamuro K, Berkovic SF, Duyk GM, Parisi J, Huttenlocher PR, Walsh CA (1996) Periventricular heterotopia: an X-linked dominant epilepsy locus causing aberrant cerebral cortical development. Neuron 16:77–87CrossRefPubMedGoogle Scholar
  23. Ferrer I (1984) A Golgi analysis of unlayered polymicrogyria. Acta Neuropathol (Berl) 65:69–76CrossRefGoogle Scholar
  24. Fink JM, Dobyns WB, Guerrini R, Hirsch BA (1997) Identification of a duplication of Xq28 associated with bilateral periventricular nodular heterotopia. Am J Hum Genet 61:379–387CrossRefPubMedGoogle Scholar
  25. Fox JW, Lamperti ED, Eksioglu YZ, Hong SE, Feng Y, Graham DA, Scheffer IE, Dobyns WB, Hirsch BA, Radtke RA, Berkovic SF, Huttenlocher PR, Walsh CA (1998) Mutations in Filamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia. Neuron 21:1315–1325CrossRefPubMedGoogle Scholar
  26. Friede R (1989) Developmental neuropathology. Springer, Berlin Heidelberg New YorkGoogle Scholar
  27. Galaburda AM, Sherman GF, Rosen GD, Aboitiz F, Geschwind N (1985) Developmental dyslexia: four consecutive patients with cortical anomalies. Ann Neurol 18:222–233CrossRefPubMedGoogle Scholar
  28. Geerdink N, Rotteveel JJ, Lammens M, Sistermans EA, Heikens GT, Gabreels FJ, Mullaart RA, Hamel BC (2002) MECP2 mutation in a boy with severe neonatal encephalopathy: clinical, neuropathological and molecular findings. Neuropediatrics 33:33–36CrossRefPubMedGoogle Scholar
  29. Gleeson JG, Allen KM, Fox JW, Lamperti ED, Berkovic S, Scheffer I, Cooper EC, Dobyns WB, Minnerath SR, Ross ME, Walsh CA (1998) doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein. Cell 92:63–72CrossRefPubMedGoogle Scholar
  30. Gleeson JG, Minnerath SR, Fox JW, Allen KM, Luo RF, Hong SE, Berg MJ, Kuzniecky R, Reitnauer PJ, Borgatti R, Mira AP, Guerrini R, Holmes GL, Rooney CM, Berkovic S, Scheffer I, Cooper EC, Ricci S, Cusmai R, Crawford TO, Leroy R, Andermann E, Wheless JW, Dobyns WB, Walsh CA, et al. (1999) Characterization of mutations in the gene doublecortin in patients with double cortex syndrome. Ann Neurol 45:146–153CrossRefPubMedGoogle Scholar
  31. Gleeson JG, Luo RF, Grant PE, Guerrini R, Huttenlocher PR, Berg MJ, Ricci S, Cusmai R, Wheless JW, Berkovic S, Scheffer I, Dobyns WB, Walsh CA (2000a) Genetic and neuroradiological heterogeneity of double cortex syndrome. Ann Neurol 47:265–269CrossRefGoogle Scholar
  32. Gleeson JG, Minnerath S, Kuzniecky RI, Dobyns WB, Young ID, Ross ME, Walsh CA (2000b) Somatic and germline mosaic mutations in the doublecortin gene are associated with variable phenotypes. Am J Hum Genet 67:574–581CrossRefGoogle Scholar
  33. Gorlin JB, Yamin R, Egan S, Stewart M, Stossel TP, Kwiatkowski DJ, Hartwig JH (1990) Human endothelial actin-binding protein (ABP-280, nonmuscle filamin): a molecular leaf spring. J Cell Biol 111:1089–1105CrossRefPubMedGoogle Scholar
  34. Granata T, Farina L, Faiella A, Cardini R, D’Incerti L, Boncinelli E, Battaglia G (1997) Familial schizencephaly associated with EMX2 mutation. Neurology 48:1403–1406PubMedGoogle Scholar
  35. Guerreiro MM, Andermann E, Guerrini R, Dobyns WB, Kuzniecky R, Silver K, Van Bogaert P, Gillain C, David P, Ambrosetto G, Rosati A, Bartolomei F, Parmeggiani A, Paetau R, Salonen O, Ignatius J, Borgatti R, Zucca C, Bastos AC, Palmini A, Fernandes W, Montenegro MA, Cendes F, Andermann F (2000) Familial perisylvian polymicrogyria: a new familial syndrome of cortical maldevelopment. Ann Neurol 48:39–48CrossRefPubMedGoogle Scholar
  36. Guerrini R (2004) Do heterotopic neurons think? Neurology, 62:1Google Scholar
  37. Guerrini R, Carrozzo R (2001a) Epilepsy and genetic malformations of the cerebral cortex. Am J Med Genet 106:160–173CrossRefGoogle Scholar
  38. Guerrini R, Carrozzo R (2001b) Epileptogenic brain malformations: clinical presentation, malformative patterns and indications for genetic testing. Seizure 10:532–543CrossRefGoogle Scholar
  39. Guerrini R, Filippi T (2005) Neuronal migration disorders, genetics, and epileptogenesis. J Child Neurol 20:287–299PubMedCrossRefGoogle Scholar
  40. Guerrini R, Dravet C, Raybaud C, Roger J, Bureau M, Battaglia A, Livet MO, Colicchio G, Robain O (1992a) Neurological findings and seizure outcome in children with bilateral opercular macrogyric-like changes detected by MRI. Dev Med Child Neurol 34:694–705CrossRefGoogle Scholar
  41. Guerrini R, Dravet C, Raybaud C, Roger J, Bureau M, Battaglia A, Livet MO, Gambarelli D, Robain O (1992b) Epilepsy and focal gyral anomalies detected by MRI: electroclinico-morphological correlations and follow-up. Dev Med Child Neurol 34:706–718CrossRefGoogle Scholar
  42. Guerrini R, Dubeau F, Dulac O, Barkovich AJ, Kuzniecky R, Fett C, Jones-Gotman M, Canapicchi R, Cross H, Fish D, Bonanni P, Jambaque I, Andermann F (1997) Bilateral parasagittal parietooccipital polymicrogyria and epilepsy. Ann Neurol 41:65–73CrossRefPubMedGoogle Scholar
  43. Guerrini R, Genton P, Bureau M, Parmeggiani A, Salas-Puig X, Santucci M, Bonanni P, Ambrosetto G, Dravet C (1998) Multilobar polymicrogyria, intractable drop attack seizures, and sleep-related electrical status epilepticus. Neurology 51:504–512PubMedGoogle Scholar
  44. Guerrini R, Barkovich AJ, Sztriha L, Dobyns WB (2000) Bilateral frontal polymicrogyria: a newly recognized brain malformation syndrome. Neurology 54:909–913PubMedGoogle Scholar
  45. Guerrini R, Holthausen H, Parmeggiani L, Chiron C (2002) Epilepsy and malformations of the cerebral cortex. In: Roger JBM, Dravet C, Genton P, Tassinari CA, Wolf P (eds) Epileptic syndromes in infancy, childhood and adolescence. John Libbey, London, pp 457–579Google Scholar
  46. Guerrini R, Moro F, Andermann E, Hughes E, D’Agostino D, Carrozzo R, Bernasconi A, Flinter F, Parmeggiani L, Volzone A, Parrini E, Mei D, Jarosz JM, Morris RG, Pratt P, Tortorella G, Dubeau F, Andermann F, Dobyns WB, Das S (2003) Nonsyndromic mental retardation and cryptogenic epilepsy in women with doublecortin gene mutations. Ann Neurol 54:30–37CrossRefPubMedGoogle Scholar
  47. Guerrini R, Mei D, Sisodiya S, Sicca F, Harding B, Takahashi Y, Dorn T, Yoshida A, Campistol J, Kramer G, Moro F, Dobyns WB, Parrini E (2004) Germline and mosaic mutations of FLN1 in men with periventricular heterotopia. Neurology 63:51–56PubMedGoogle Scholar
  48. Guion-Almeida ML, Richieri-Costa A (1999) Frontonasal dysplasia, macroblepharon, eyelid colobomas, ear anomalies, macrostomia, mental retardation, and CNS structural anomalies. A new syndrome? Clin Dysmorphol 8:1–4PubMedCrossRefGoogle Scholar
  49. Harding B, Copp A (1997) Malformations of the nervous system. In: Graham J, Lantos PL (eds) Greenfields neuropathology. Edward Arnold, London, pp 521–538Google Scholar
  50. Hattori M, Adachi H, Tsujimoto M, Arai H, Inoue K (1994) Miller–Dieker lissencephaly gene encodes a subunit of brain platelet-activating factor acetylhydrolase [corrected]. Nature 370:216–218CrossRefPubMedGoogle Scholar
  51. Hiesberger T, Trommsdorff M, Howell BW, Goffinet A, Mumby MC, Cooper JA, Herz J (1999) Direct binding of reelin to VLDL receptor and apoE receptor 2 induces tyrosine phosphorylation of disabled-1 and modulates tau phosphorylation. Neuron 24:481–489CrossRefPubMedGoogle Scholar
  52. Hock RS, Davis G, Speicher DW (1990) Purification of human smooth muscle filamin and characterization of structural domains and functional sites. Biochemistry 29:9441–9451CrossRefPubMedGoogle Scholar
  53. Hong SE, Shugart YY, Huang DT, Shahwan SA, Grant PE, Hourihane JO, Martin ND, Walsh CA (2000) Autosomal recessive lissencephaly with cerebellar hypoplasia (LCH) is associated with human reelin gene mutations. Nat Genet 26:93–96CrossRefPubMedGoogle Scholar
  54. Hosley MA, Abroms IF, Ragland RL (1992) Schizencephaly: case report of familial incidence. Pediatr Neurol 8:148–150CrossRefPubMedGoogle Scholar
  55. Jansen A, Andermann E (2005) Genetics of the polymicrogyria syndromes. J Med Genet 42:369–378CrossRefPubMedGoogle Scholar
  56. Kato M, Dobyns WB (2003) Lissencephaly and the molecular basis of neuronal migration. Hum Mol Genet 12:89–96CrossRefGoogle Scholar
  57. Kato M, Das S, Petras K, Kitamura K, Morohashi K, Abuelo DN, Barr M, Bonneau D, Brady AF, Carpenter NJ, Cipero KL, Frisone F, Fukuda T, Guerrini R, Iida E, Itoh M, Lewanda AF, Nanba Y, Oka A, Proud VK, Saugier-Veber P, Schelley SL, Selicorni A, Shaner R, Silengo M, Stewart F, Sugiyama N, Toyama J, Toutain A, Vargas AL, Yanazawa M, Zackai EH, Dobyns WB (2004) Mutations of ARX are associated with striking pleiotropy and consistent genotype–phenotype correlation. Hum Mutat 23:147–159CrossRefPubMedGoogle Scholar
  58. Keng WT, Pilz DT, Minns B, FitzPatrick DR (2003) A3243G mitochondrial mutation associated with polymicrogyria. Dev Med Child Neurol 45:704–708CrossRefPubMedGoogle Scholar
  59. Kitamura K, Yanazawa M, Sugiyama N, Miura H, Iizuka-Kogo A, Kusaka M, Omichi K, Suzuki R, Kato-Fukui Y, Kamiirisa K, Matsuo M, Kamijo S, Kasahara M, Yoshioka H, Ogata T, Fukuda T, Kondo I, Kato M, Dobyns WB, Yokoyama M, Morohashi K (2002) Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans. Nat Genet 32:359–369CrossRefPubMedGoogle Scholar
  60. Kothare SV, VanLandingham K, Armon C, Luther JS, Friedman A, Radtke RA (1998) Seizure onset from periventricular nodular heterotopias: depth-electrode study. Neurology 51:1723–1727PubMedGoogle Scholar
  61. Kuzniecky R, Andermann F, Guerrini R, Study CMC (1993a) Congenital bilateral perisylvian syndrome: study of 31 patients. The Lancet 341:608–612CrossRefGoogle Scholar
  62. Kuzniecky RI (1994) Magnetic resonance imaging in developmental disorders of the cerebral cortex. Epilepsia 35(6):S44–S56PubMedCrossRefGoogle Scholar
  63. Kuzniecky R, Andermann F, Guerrino R, Study CC (1993b) Seizures in the congenital bilateral Perisylvian syndrome. Epilepsia 34(2):65Google Scholar
  64. Leventer RJ, Cardoso C, Ledbetter DH, Dobyns WB (2001) LIS1 missense mutations cause milder lissencephaly phenotypes including a child with normal IQ. Neurology 57:416–422PubMedGoogle Scholar
  65. Lo Nigro C, Chong CS, Smith AC, Dobyns WB, Carrozzo R, Ledbetter DH (1997) Point mutations and an intragenic deletion in LIS1, the lissencephaly causative gene in isolated lissencephaly sequence and Miller–Dieker syndrome. Hum Mol Genet 6:157–164CrossRefPubMedGoogle Scholar
  66. Loo DT, Kanner SB, Aruffo A (1998) Filamin binds to the cytoplasmic domain of the beta1-integrin. Identification of amino acids responsible for this interaction. J Biol Chem 273:23304–23312CrossRefPubMedGoogle Scholar
  67. Meyer S, Zuerbig S, Cunningham CC, Hartwig JH, Bissell T, Gardner K, Fox JE (1997) Identification of the region in actin-binding protein that binds to the cytoplasmic domain of glycoprotein IBalpha. J Biol Chem 272:2914–2919CrossRefPubMedGoogle Scholar
  68. Mitchell T, Free SL, Williamson KA, Stevens JM, Churchill AJ, Hanson IM, Shorvon SD, Moore AT, van Heyningen V, Sisodiya SM (2003) Polymicrogyria and absence of pineal gland due to PAX6 mutation. Ann Neurol 53:658–663CrossRefPubMedGoogle Scholar
  69. Morioka T, Nishio S, Sasaki M, Yoshida T, Kuwabara Y, Ohta M, Fukui M (1999) Functional imaging in periventricular nodular heterotopia with the use of FDG-PET and HMPAO-SPECT. Neurosurg Rev 22:41–44CrossRefPubMedGoogle Scholar
  70. Moro F, Carrozzo R, Veggiotti P, Tortorella G, Toniolo D, Volzone A, Guerrini R (2002) Familial periventricular heterotopia: missense and distal truncating mutations of the FLN1 gene. Neurology 58:916–921PubMedGoogle Scholar
  71. Morris NR, Efimov VP, Xiang X (1998) Nuclear migration, nucleokinesis and lissencephaly. Trends Cell Biol 8:467–470CrossRefPubMedGoogle Scholar
  72. Noegel AA, Leiting B, Witke W, Gurniak C, Harloff C, Hartmann H, Wiesmuller E, Schleicher M (1989) Biological roles of actin-binding proteins in Dictyostelium discoideum examined using genetic techniques. Cell Motil Cytoskeleton 14:69–74CrossRefPubMedGoogle Scholar
  73. Ohira R, Zhang YH, Guo W, Dipple K, Shih SL, Doerr J, Huang BL, Fu LJ, Abu-Khalil A, Geschwind D, McCabe ER (2002) Human ARX gene: genomic characterization and expression. Mol Genet Metab 77:179–188CrossRefPubMedGoogle Scholar
  74. Ott I, Fischer EG, Miyagi Y, Mueller BM, Ruf W (1998) A role for tissue factor in cell adhesion and migration mediated by interaction with actin-binding protein 280. J Cell Biol 140:1241–1253CrossRefPubMedGoogle Scholar
  75. Parrini E, Mei D, Wright M, Dorn T, Guerrini R (2004) Mosaic mutations of the FLN1 gene cause a mild phenotype in patients with periventricular heterotopia. Neurogenetics 5:191–196CrossRefPubMedGoogle Scholar
  76. Parrini E, Ramazzotti A, Dobyns WB, Mei D, Moro F, Veggiotti P, Marini C, Brilstra EH, Dalla Bernardina B, Goodwin L, Bodell A, Jones MC, Nangeroni M, Palmeri S, Said E, Sander JW, Striano P, Takahashi Y, Van Maldergem L, Leonardi G, Wright M, Walsh CA, Guerrini R. (2006) Periventricular heterotopia: phenotypic heterogeneity and correlation with Filamin A mutations. Brain (in press)Google Scholar
  77. Piao X, Basel-Vanagaite L, Straussberg R, Grant PE, Pugh EW, Doheny K, Doan B, Hong SE, Shugart YY, Walsh CA (2002) An autosomal recessive form of bilateral frontoparietal polymicrogyria maps to chromosome 16q12.2–21. Am J Hum Genet 70:1028–1033CrossRefPubMedGoogle Scholar
  78. Piao X, Hill RS, Bodell A, Chang BS, Basel-Vanagaite L, Straussberg R, Dobyns WB, Qasrawi B, Winter RM, Innes AM, Voit T, Ross ME, Michaud JL, Descarie JC, Barkovich AJ, Walsh CA (2004) G protein-coupled receptor-dependent development of human frontal cortex. Science 303:2033–2036CrossRefPubMedGoogle Scholar
  79. Pilz DT, Matsumoto N, Minnerath S, Mills P, Gleeson JG, Allen KM, Walsh CA, Barkovich AJ, Dobyns WB, Ledbetter DH, Ross ME (1998) LIS1 and XLIS (DCX) mutations cause most classical lissencephaly, but different patterns of malformation. Hum Mol Genet 7:2029–2037CrossRefPubMedGoogle Scholar
  80. Pilz DT, Kuc J, Matsumoto N, Bodurtha J, Bernadi B, Tassinari CA, Dobyns WB, Ledbetter DH (1999) Subcortical band heterotopia in rare affected males can be caused by missense mutations in DCX (XLIS) or LIS1. Hum Mol Genet 8:1757–1760CrossRefPubMedGoogle Scholar
  81. des Portes V, Pinard JM, Billuart P, Vinet MC, Koulakoff A, Carrie A, Gelot A, Dupuis E, Motte J, Berwald-Netter Y, Catala M, Kahn A, Beldjord C, Chelly J (1998) A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome. Cell 92:51–61CrossRefPubMedGoogle Scholar
  82. Reiner O, Carrozzo R, Shen Y, Wehnert M, Faustinella F, Dobyns WB, Caskey CT, Ledbetter DH (1993) Isolation of a Miller–Dieker lissencephaly gene containing G protein b-subunit-like repeats. Nature 364:717–721CrossRefPubMedGoogle Scholar
  83. Robain O (1996) Introduction to the pathology of cerebral cortical dysplasia. In: Guerrini R, Andermann F, Canapicchi R, Roger J, Zifkin B, Pfanner P (eds) Dysplasias of cerebral cortex and epilepsy. Lippincott-Raven, Philadelphia, pp 1–9Google Scholar
  84. Ross ME, Swanson K, Dobyns WB (2001) Lissencephaly with cerebellar hypoplasia (LCH): a heterogeneous group of cortical malformations. Neuropediatrics 32:256–263CrossRefPubMedGoogle Scholar
  85. Sapir T, Elbaum M, Reiner O (1997) Reduction of microtubule catastrophe events by LIS1, platelet-activating factor acetylhydrolase subunit. EMBO J 16:6977–6984CrossRefPubMedGoogle Scholar
  86. Sharma CP, Ezzell RM, Arnaout MA (1995) Direct interaction of filamin (ABP-280) with the beta 2-integrin subunit CD18. J Immunol 154:3461–3470PubMedGoogle Scholar
  87. Sheen VL, Dixon PH, Fox JW, Hong SE, Kinton L, Sisodiya SM, Duncan JS, Dubeau F, Scheffer IE, Schachter SC, Wilner A, Henchy R, Crino P, Kamuro K, DiMario F, Berg M, Kuzniecky R, Cole AJ, Bromfield E, Biber M, Schomer D, Wheless J, Silver K, Mochida GH, Berkovic SF, Andermann F, Andermann E, Dobyns WB, Wood NW, Walsh CA (2001) Mutations in the X-linked filamin 1 gene cause periventricular nodular heterotopia in males as well as in females. Hum Mol Genet 10:1775–1783CrossRefPubMedGoogle Scholar
  88. Sheen VL, Topcu M, Berkovic S, Yalnizoglu D, Blatt I, Bodell A, Hill RS, Ganesh VS, Cherry TJ, Shugart YY, Walsh CA (2003) Autosomal recessive form of periventricular heterotopia. Neurology 60:1108–1112PubMedGoogle Scholar
  89. Sheen VL, Ganesh VS, Topcu M, Sebire G, Bodell A, Hill RS, Grant PE, Shugart YY, Imitola J, Khoury SJ, Guerrini R, Walsh CA (2004) Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex. Nat Genet 36:69–76CrossRefPubMedGoogle Scholar
  90. Sicca F, Kelemen A, Genton P, Das S, Mei D, Moro F, Dobyns WB, Guerrini R (2003a) Mosaic mutations of the LIS1 gene cause subcortical band heterotopia. Neurology 61:1042–1046Google Scholar
  91. Sicca F, Silengo M, Parrini E, Ferrero GB, Guerrini R (2003b) Subcortical band heterotopia with simplified gyral pattern and syndactyly. Am J Med Genet A 119:207–210CrossRefGoogle Scholar
  92. Stromme P, Mangelsdorf ME, Shaw MA, Lower KM, Lewis SM, Bruyere H, Lutcherath V, Gedeon AK, Wallace RH, Scheffer IE, Turner G, Partington M, Frints SG, Fryns JP, Sutherland GR, Mulley JC, Gecz J (2002) Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy. Nat Genet 30:441–445PubMedCrossRefGoogle Scholar
  93. Sztriha L, Guerrini R, Harding B, Stewart F, Chelloug N, Johansen JG (2004) Clinical, MRI, and pathological features of polymicrogyria in chromosome 22q11 deletion syndrome. Am J Med Genet A 127:313–317CrossRefPubMedGoogle Scholar
  94. Van Bogaert P, Donner C, David P, Rodesch F, Avni EF, Szliwowski HB (1996) Congenital bilateral perisylvian syndrome in a monozygotic twin with intra-uterine death of the co-twin. Dev Med Child Neurol 38:166–170PubMedCrossRefGoogle Scholar
  95. Villard L, Nguyen K, Cardoso C, Martin CL, Weiss AM, Sifry-Platt M, Grix AW, Graham JM Jr, Winter RM, Leventer RJ, Dobyns WB (2002) A locus for bilateral perisylvian polymicrogyria maps to Xq28. Am J Hum Genet 70:1003–1008CrossRefPubMedGoogle Scholar
  96. Wieck G, Leventer RJ, Squier WM, Jansen A, Andermann E, Dubeau F, Ramazzotti A, Guerrini R, Dobyns WB (2005) Periventricular nodular heterotopia with overlying polymicrogyria. Brain 128:2811–2821CrossRefPubMedGoogle Scholar
  97. Zhang W, Han SW, McKeel DW, Goate A, Wu JY (1998) Interaction of presenilins with the filamin family of actin-binding proteins. J Neurosci 18:914–922 PubMedGoogle Scholar

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© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Epilepsy, Neurophysiology and Neurogenetics Unit, Division of Child Neurology and PsychiatryUniversity of Pisa and Research Institute Stella Maris FoundationCalambrone, PisaItaly

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