1932

Abstract

Malformations of cortical development encompass heterogeneous groups of structural brain anomalies associated with complex neurodevelopmental disorders and diverse genetic and nongenetic etiologies. Recent progress in understanding the genetic basis of brain malformations has been driven by extraordinary advances in DNA sequencing technologies. For example, somatic mosaic mutations that activate mammalian target of rapamycin signaling in cortical progenitor cells during development are now recognized as the cause of hemimegalencephaly and some types of focal cortical dysplasia. In addition, research on brain development has begun to reveal the cellular and molecular bases of cortical gyrification and axon pathway formation, providing better understanding of disorders involving these processes. New neuroimaging techniques with improved resolution have enhanced our ability to characterize subtle malformations, such as those associated with intellectual disability and autism. In this review, we broadly discuss cortical malformations and focus on several for which genetic etiologies have elucidated pathogenesis.

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2019-01-24
2024-03-28
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Literature Cited

  1. 1.  Bystron I, Blakemore C, Rakic P 2008. Development of the human cerebral cortex: Boulder Committee revisited. Nat. Rev. Neurosci. 9:110–32
    [Google Scholar]
  2. 2.  Barkovich AJ, Guerrini R, Kuzniecky RI, Jackson GD, Dobyns WB 2012. A developmental and genetic classification for malformations of cortical development: update 2012. Brain 135:1348–69
    [Google Scholar]
  3. 3.  Guerrini R, Dobyns W 2014. Malformations of cortical development: clinical features and genetic causes. Lancet Neurol 13:710–26
    [Google Scholar]
  4. 4.  Kuzniecky RI 1994. Magnetic resonance imaging in developmental disorders of the cerebral cortex. Epilepsia 35:Suppl. 6S44–56
    [Google Scholar]
  5. 5.  Leventer RJ, Phelan EM, Coleman LT, Kean MJ, Jackson GD, Harvey AS 1999. Clinical and imaging features of cortical malformations in childhood. Neurology 53:715–22
    [Google Scholar]
  6. 6.  Barkovich AJ, Dobyns WB, Guerrini R 2015. Malformations of cortical development and epilepsy. Cold Spring Harb. Perspect. Med. 5:a022392
    [Google Scholar]
  7. 7.  Jamuar SS, Lam AT, Kircher M, D'Gama AM, Wang J et al. 2014. Somatic mutations in cerebral cortical malformations. N. Engl. J. Med. 371:733–43
    [Google Scholar]
  8. 8.  Li J, Cai T, Jiang Y, Chen H, He X et al. 2016. Genes with de novo mutations are shared by four neuropsychiatric disorders discovered from NPdenovo database. Mol. Psychiatry 21:290–97
    [Google Scholar]
  9. 9.  Wilfert AB, Sulovari A, Turner TN, Coe BP, Eichler EE 2017. Recurrent de novo mutations in neurodevelopmental disorders: properties and clinical implications. Genome Med 9:101
    [Google Scholar]
  10. 10.  Lombroso CT 2000. Can early postnatal closed head injury induce cortical dysplasia. Epilepsia 41:245–53
    [Google Scholar]
  11. 11.  Sarnat HB 1987. Disturbance of late neuronal migrations in the perinatal period. Am. J. Dis. Child 141:969–80
    [Google Scholar]
  12. 12.  Hong SJ, Bernhardt BC, Gill RS, Bernasconi N, Bernasconi A 2017. The spectrum of structural and functional network alterations in malformations of cortical development. Brain 140:2133–43
    [Google Scholar]
  13. 13.  Happle R 1997. A rule concerning the segmental manifestation of autosomal dominant skin disorders: review of clinical examples providing evidence for dichotomous types of severity. Arch. Dermatol. 133:1505–9
    [Google Scholar]
  14. 14.  Jansen LA, Mirzaa GM, Ishak GE, O'Roak BJ, Hiatt JB et al. 2015. PI3K/AKT pathway mutations cause a spectrum of brain malformations from megalencephaly to focal cortical dysplasia. Brain 138:1613–28
    [Google Scholar]
  15. 15.  Qin W, Chan JA, Vinters HV, Mathern GW, Franz DN et al. 2010. Analysis of TSC cortical tubers by deep sequencing of TSC1, TSC2 and KRAS demonstrates that small second-hit mutations in these genes are rare events. Brain Pathol 20:1096–105
    [Google Scholar]
  16. 16.  Mallinger G, Kindron D, Schreiber L, Ben-Sira L, Hoffman C et al. 2007. Prenatal diagnosis of malformations of cortical development by dedicated neurosonography. Ultrasound Obstet. Gynecol. 29:178–91
    [Google Scholar]
  17. 17.  Barkovich AJ, Kuzniecky RI, Dobyns WB, Jackson GD, Becker LE et al. 1996. A classification scheme for malformations of cortical development. Neuropediatrics 27:59–63
    [Google Scholar]
  18. 18.  Desikan RS, Barkovich AJ 2016. Malformations of cortical development. Ann. Neurol. 80:797–810
    [Google Scholar]
  19. 19.  Romero DM, Bahi-Buisson N, Francis F 2018. Genetics and mechanisms leading to human cortical malformations. Semin. Cell Dev. Biol. 76:33–75
    [Google Scholar]
  20. 20.  Thornton GK, Woods CG 2009. Primary microcephaly: Do all roads lead to Rome?. Trends Genet 25:501–10
    [Google Scholar]
  21. 21.  Yu TW, Mochida GH, Tischfield DJ, Sgaier SK, Flores-Sarnat L et al. 2010. Mutations in WDR62, encoding a centrosome-associated protein, cause microcephaly with simplified gyri and abnormal cortical architecture. Nat. Gen. 42:1015–20
    [Google Scholar]
  22. 22.  Bahi-Buisson N, Poirier K, Fourniol F, Saillaour Y, Valence S et al. 2014. The wide spectrum of tubulinopathies: What are the key features for the diagnosis?. Brain 137:1676–700
    [Google Scholar]
  23. 23.  Di Donato N, Chiari S, Mirzaa GM, Aldinger K, Parrini E et al. 2017. Lissencephaly: expanded imaging and clinical classification. Am. J. Med. Genet. 173A:1473–88
    [Google Scholar]
  24. 24.  Bahi-Buisson N, Poirier N, Boddaert N, Fallet-Bianco C, Specchio N et al. 2010. GPR56-related bilateral frontoparietal polymicrogyria: further evidence for an overlap with the cobblestone complex. Brain 133:3194–209
    [Google Scholar]
  25. 25.  Rivas L, Blanco O, Torreira C, Repáraz A, Melcón C, Amado A 2017. Pontocerebellar hypoplasia secondary to CASK gene deletion: case report. Rev. Child. Pediatr. 88:529–33
    [Google Scholar]
  26. 26.  Rakic P 1988. Specification of cerebral cortical areas. Science 241:170–76
    [Google Scholar]
  27. 27.  Welker W 1990. Why does cerebral cortex fissure and fold? A review of determinants of gyri and sulci in cerebral cortex. Cerebral Cortex 8B EG Jones, A Peters 3–136 Berlin: Springer
    [Google Scholar]
  28. 28.  Anderson SA, Eisenstat DD, Shi L, Rubenstein JL 1997. Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes. Science 278:474–76
    [Google Scholar]
  29. 29.  Chu J, Anderson SA 2015. Development of cortical interneurons. Neuropsychopharmacology 40:16–23
    [Google Scholar]
  30. 30.  Lui JH, Hansen DV, Kriegstein AR 2011. Development and evolution of the human neocortex. Cell 146:18–36
    [Google Scholar]
  31. 31.  Sun T, Hevner RF 2014. Growth and folding of the mammalian cerebral cortex: from molecules to malformations. Nat. Rev. Neurosci. 15:217–32
    [Google Scholar]
  32. 32.  Kowalczyk T, Pontious A, Englund C, Daza RA, Bedogni F et al. 2009. Intermediate neuronal progenitors (basal progenitors) produce pyramidal-projection neurons for all layers of cerebral cortex. Cereb. Cortex 19:2439–50
    [Google Scholar]
  33. 33.  Kriegstein A, Noctor S, Martínez-Cerdeño V 2006. Patterns of neural stem and progenitor cell division may underlie evolutionary cortical expansion. Nat. Rev. Neurosci. 7:883–90
    [Google Scholar]
  34. 34.  Hevner RF 2016. Evolution of the mammalian dentate gyrus. J. Comp. Neurol. 524:578–94
    [Google Scholar]
  35. 35.  Smart IH, Dehay C, Giroud P, Berland M, Kennedy H 2002. Unique morphological features of the proliferative zones and postmitotic compartments of the neural epithelium giving rise to striate and extrastriate cortex in the monkey. Cereb. Cortex 12:37–53
    [Google Scholar]
  36. 36.  Hansen DV, Lui JH, Parker PR, Kriegstein AR 2010. Neurogenic radial glia in the outer subventricular zone of human neocortex. Nature 464:554–61
    [Google Scholar]
  37. 37.  Nowakowski TJ, Bhaduri A, Pollen AA, Alvarado B, Mostajo-Radji MA et al. 2017. Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex. Science 358:1318–23
    [Google Scholar]
  38. 38.  Nowakowski TJ, Pollen AA, Sandoval-Espinosa C, Kriegstein AR 2016. Transformation of the radial glia scaffold demarcates two stages of human cerebral cortex development. Neuron 91:1219–27
    [Google Scholar]
  39. 39.  de Juan Romero C, Bruder C, Tomasello U, Sanz-Anquela JM, Borrell V 2015. Discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly. EMBO J 34:1859–74
    [Google Scholar]
  40. 40.  Matsumoto N, Shinmyo Y, Ichikawa Y, Kawasaki H 2017. Gyrification of the cerebral cortex requires FGF signaling in the mammalian brain. eLife 6:e29285
    [Google Scholar]
  41. 41.  Malik S, Vinukonda G, Vose LR, Diamond D, Bhimavarapu BB et al. 2013. Neurogenesis continues in the third trimester of pregnancy and is suppressed by premature birth. J. Neurosci. 33:411–23
    [Google Scholar]
  42. 42.  Sorrells SF, Paredes MF, Cebrian-Silla A, Sandoval K, Qi D et al. 2018. Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature 555:377–81
    [Google Scholar]
  43. 43.  Greig LC, Woodworth MB, Galazo MJ, Padmanabhan H, Macklis JD 2013. Molecular logic of neocortical projection neuron specification, development and diversity. Nat. Rev. Neurosci. 14:755–69
    [Google Scholar]
  44. 44.  Bedogni F, Hodge RD, Elsen GE, Nelson BR, Daza RA et al. 2010. Tbr1 regulates regional and laminar identity of postmitotic neurons in developing neocortex. PNAS 107:13129–34
    [Google Scholar]
  45. 45.  Hevner RF 2005. The cerebral cortex malformation in thanatophoric dysplasia: neuropathology and pathogenesis. Acta Neuropathol 110:208–21
    [Google Scholar]
  46. 46.  Blümcke I, Thom M, Aronica E, Armstrong DD, Vinters HV et al. 2011. The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission. Epilepsia 52:158–74
    [Google Scholar]
  47. 47.  Blümcke I, Spreafico R, Haaker G, Coras R, Kobow K et al. 2017. Histopathological findings in brain tissue obtained during epilepsy surgery. N. Engl. J. Med. 377:1648–56
    [Google Scholar]
  48. 48.  Vanhaesebroeck B, Stephens L, Hawkins P 2012. PI3K signalling: the path to discovery and understanding. Nat. Rev. Mol. Cell Biol. 13:195–203
    [Google Scholar]
  49. 49.  Saxton RA, Sabatini DM 2017. mTOR signaling in growth, metabolism, and disease. Cell 168:960–76
    [Google Scholar]
  50. 50.  Janku F, Yap TA, Meric-Bernstam F 2018. Targeting the PI3K pathway in cancer: Are we making headway?. Nat. Rev. Clin. Oncol. 15:273–91
    [Google Scholar]
  51. 51.  Iwata T, Hevner RF 2009. Fibroblast growth factor signalling in development of the cerebral cortex. Dev. Growth Differ. 51:299–323
    [Google Scholar]
  52. 52.  Kunova Bosakova M, Varecha M, Hampl M, Duran I, Nita A et al. 2018. Regulation of ciliary function by fibroblast growth factor signaling identifies FGFR3-related disorders achondroplasia and thanatophoric dysplasia as ciliopathies. Hum. Mol. Genet. 27:1093–105
    [Google Scholar]
  53. 53.  Puffenberger EG, Strauss KA, Ramsey KE, Craig DW, Stephan DA et al. 2007. Polyhydramnios, megalencephaly and symptomatic epilepsy caused by a homozygous 7-kilobase deletion in LYK5. . Brain 130:1929–41
    [Google Scholar]
  54. 54.  Lindhurst MJ, Sapp JC, Teer JK, Johnston JJ, Finn EM et al. 2011. A mosaic activating mutation in AKT1 associated with the Proteus syndrome. N. Engl. J. Med. 365:611–19
    [Google Scholar]
  55. 55.  Lee JH, Huynh M, Silhavy JL, Kim S, Dixon-Salazar T et al. 2012. De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly. Nat. Genet. 44:941–45
    [Google Scholar]
  56. 56.  Poduri A, Evrony GD, Cai X, Elhosary PC, Beroukhim R et al. 2012. Somatic activation of AKT3 causes hemispheric developmental brain malformations. Neuron 74:41–48
    [Google Scholar]
  57. 57.  Rivière JB, Mirzaa GM, O'Roak BJ, Beddaoui M, Alcantara D et al. 2012. De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat. Genet 44:934–40
    [Google Scholar]
  58. 58.  Borrie SC, Brems H, Legius E, Bagni C 2017. Cognitive dysfunctions in intellectual disabilities: the contributions of the Ras-MAPK and PI3K-AKT-mTOR pathways. Annu. Rev. Genom. Hum. Genet. 18:115–42
    [Google Scholar]
  59. 59.  Reijnders MRF, Kousi M, van Woerden GM, Klein M, Bralten J et al. 2017. Variation in a range of mTOR-related genes associates with intracranial volume and intellectual disability. Nat. Commun. 8:1052
    [Google Scholar]
  60. 60.  Yeung KS, Tso WWY, Ip JJK, Mak CCY, Leung GKC et al. 2017. Identification of mutations in the PI3K-AKT-mTOR signalling pathway in patients with macrocephaly and developmental delay and/or autism. Mol. Autism 8:66
    [Google Scholar]
  61. 61.  Alcantara D, Timms AE, Gripp K, Baker L, Park K et al. 2017. Mutations of AKT3 are associated with a wide spectrum of developmental disorders including extreme megalencephaly. Brain 140:2610–22
    [Google Scholar]
  62. 62.  D'Gama AM, Woodworth MB, Hossain AA, Bizzotto S, Hatem NE et al. 2017. Somatic mutations activating the mTOR pathway in dorsal telencephalic progenitors cause a continuum of cortical dysplasia. Cell Rep 21:3754–66
    [Google Scholar]
  63. 63.  Baek ST, Copeland B, Yun EJ, Kwon SK, Guemez-Gamboa A et al. 2015. AKT3-FOXG1-reelin network underlies defective migration in human focal malformations of cortical development. Nat. Med. 21:1445–54
    [Google Scholar]
  64. 64.  Conti V, Pantaleo M, Barba C, Baroni G, Mei D et al. 2015. Focal dysplasia of the cerebral cortex and infantile spasms associated with somatic 1q21.1-q44 duplication including the AKT3 gene. Clin. Genet. 88:241–47
    [Google Scholar]
  65. 65.  Milone R, Valetto A, Battini R, Bertini V, Valvo G et al. 2016. Focal cortical dysplasia, microcephaly and epilepsy in a boy with 1q21.1-q21.3 duplication. Eur. J. Med. Genet. 59:278–82
    [Google Scholar]
  66. 66.  Baulac S, Ishida S, Marsan E, Miquel C, Biraben A et al. 2015. Familial focal epilepsy with focal cortical dysplasia due to DEPDC5 mutations. Ann. Neurol. 77:675–83
    [Google Scholar]
  67. 67.  Weckhuysen S, Marsan E, Lambrecq V, Marchal C, Morin-Brureau M et al. 2016. Involvement of GATOR complex genes in familial focal epilepsies and focal cortical dysplasia. Epilepsia 57:994–1003
    [Google Scholar]
  68. 68.  Jansen LA, Hevner RF, Roden WH, Hahn SH, Jung S, Gospe SM Jr 2014. Glial localization of antiquitin: implications for pyridoxine-dependent epilepsy. Ann. Neurol. 75:22–32
    [Google Scholar]
  69. 69.  Uddin M, Woodbury-Smith M, Chan A, Brunga L, Lamoureux S et al. 2017. Germline and somatic mutations in STXBP1 with diverse neurodevelopmental phenotypes. Neurol. Genet. 3:6e199
    [Google Scholar]
  70. 70.  O'Kusky J, Ye P 2012. Neurodevelopmental effects of insulin-like growth factor signaling. Front. Neuroendocrinol. 33:230–51
    [Google Scholar]
  71. 71.  Najm IM, Sarnat HB, Blümcke I 2018. Review: the international consensus classification of focal cortical dysplasia—a critical update 2018. Neuropathol. Appl. Neurobiol. 44:18–31
    [Google Scholar]
  72. 72.  Flores-Sarnat L, Sarnat HB, Dávila-Gutiérrez G, Alvarez A 2003. Hemimegalencephaly: part 2. Neuropathology suggests a disorder of cellular lineage. J. Child Neurol. 18:776–85
    [Google Scholar]
  73. 73.  Englund C, Folkerth RD, Born D, Lacy JM, Hevner RF 2005. Aberrant neuronal-glial differentiation in Taylor-type focal cortical dysplasia (type IIA/B). Acta Neuropathol 109:519–33
    [Google Scholar]
  74. 74.  Lamparello P, Baybis M, Pollard J, Hol EM, Eisenstat DD et al. 2007. Developmental lineage of cell types in cortical dysplasia with balloon cells. Brain 130:2267–76
    [Google Scholar]
  75. 75.  Orlova KA, Tsai V, Baybis M, Heuer GG, Sisodiya S et al. 2010. Early progenitor cell marker expression distinguishes type II from type I focal cortical dysplasias. J. Neuropathol. Exp. Neurol. 69:850–63
    [Google Scholar]
  76. 76.  Salamon N, Andres M, Chute DJ, Nguyen ST, Chang JW et al. 2006. Contralateral hemimicrencephaly and clinical-pathological correlations in children with hemimegalencephaly. Brain 129:352–65
    [Google Scholar]
  77. 77.  Tsai V, Parker WE, Orlova KA, Baybis M, Chi AW et al. 2014. Fetal brain mTOR signaling activation in tuberous sclerosis complex. Cereb. Cortex 24:315–27
    [Google Scholar]
  78. 78.  Boer K, Crino PB, Gorter JA, Nellist M, Jansen FE et al. 2010. Gene expression analysis of tuberous sclerosis complex cortical tubers reveals increased expression of adhesion and inflammatory factors. Brain Pathol 20:704–19
    [Google Scholar]
  79. 79.  Mühlebner A, van Scheppingen J, Hulshof HM, Scholl T, Iyer AM et al. 2016. Novel histopathological patterns in cortical tubers of epilepsy surgery patients with tuberous sclerosis complex. PLOS ONE 11:6e0157396
    [Google Scholar]
  80. 80.  Prabowo AS, Anink JJ, Lammens M, Nellist M, van den Ouweland AM et al. 2013. Fetal brain lesions in tuberous sclerosis complex: TORC1 activation and inflammation. Brain Pathol 23:45–59
    [Google Scholar]
  81. 81.  Taylor DC, Falconer MA, Bruton CJ, Corsellis JA 1971. Focal dysplasia of the cerebral cortex in epilepsy. J. Neurol. Neurosurg. Psychiatry 34:369–87
    [Google Scholar]
  82. 82.  Krueger DA, Care MM, Holland K, Agricola K, Tudor C et al. 2011. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N. Engl. J. Med. 363:1801–11
    [Google Scholar]
  83. 83.  Franz DN, Belousova E, Sparagana S, Bebin EM, Frost M et al. 2014. Everolimus for subependymal giant cell astrocytoma in patients with tuberous sclerosis complex: 2-year open-label extension of the randomised EXIST-1 study. Lancet Oncol 15:1513–20
    [Google Scholar]
  84. 84.  Parrini E, Conti V, Dobyns WB, Guerrini R 2016. Genetic basis of brain malformations. Mol. Syndromol. 7:220–33
    [Google Scholar]
  85. 85.  Guerrini R, Filippi T 2005. Neuronal migration disorders, genetics, and epileptogenesis. J. Child Neurol. 20:287–99
    [Google Scholar]
  86. 86.  Leventer RJ, Guerrini R, Dobyns WB 2008. Malformations of cortical development and epilepsy. Dialog. Clin. Neurosci. 10:47–62
    [Google Scholar]
  87. 87.  Forman MS, Squier W, Dobyns WB, Golden JA 2005. Genotypically defined lissencephalies show distinct pathologies. J. Neuropathol. Exp. Neurol. 64:847–57
    [Google Scholar]
  88. 88.  Reiner O, Carrozzo R, Shen Y, Wehnert M, Faustinella F et al. 1993. Isolation of a Miller-Dieker lissencephaly gene containing G protein beta-subunit-like repeats. Nature 364:717–21
    [Google Scholar]
  89. 89.  Cardoso C, Leventer RJ, Ward HL, Toyo-Oka K, Chung J et al. 2003. Refinement of a 400-kb critical region allows genotypic differentiation between isolated lissencephaly, Miller-Dieker syndrome, and other phenotypes secondary to deletions of 17p13.3. Am. J. Hum. Genet. 72:918–30
    [Google Scholar]
  90. 90.  Reiner O, Sapir T 2013. LIS1 functions in normal development and disease. Curr. Opin. Neurobiol. 23:951–56
    [Google Scholar]
  91. 91.  Sicca F, Kelemen A, Genton P, Das S, Mei D et al. 2003. Mosaic mutations of the LIS1 gene cause subcortical band heterotopia. Neurology 61:1042–46
    [Google Scholar]
  92. 92.  Hirotsune S, Fleck MW, Gambello MJ, Bix GJ, Chen A et al. 1998. Graded reduction of Pafah1b1 (Lis1) activity results in neuronal migration defects and early embryonic lethality. Nat. Genet. 19:333–39
    [Google Scholar]
  93. 93.  Keays DA, Tian G, Poirier K, Huang GJ, Siebold C et al. 2007. Mutations in alpha-tubulin cause abnormal neuronal migration in mice and lissencephaly in humans. Cell 128:45–57
    [Google Scholar]
  94. 94.  Fallet-Bianco C, Loeuillet L, Poirier K, Loget P, Chapon F et al. 2008. Neuropathological phenotype of a distinct form of lissencephaly associated with mutations in TUBA1A. . Brain 131:2304–20
    [Google Scholar]
  95. 95.  Poirier K, Lebrun N, Broix L, Tian G, Saillour Y et al. 2013. Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly. Nat. Genet 45:639–67
    [Google Scholar]
  96. 96.  Colasante G, Collombat P, Raimondi V, Bonanomi D, Ferrai C et al. 2008. Arx is a direct target of Dix2 and thereby contributes to the tangential migration of GABAergic interneurons. J. Neurosci. 28:10674–86
    [Google Scholar]
  97. 97.  Simonet JC, Sunnen CN, Wu J, Golden JA, Marsh ED 2015. Conditional loss of Arx from the developing dorsal telencephalon results in behavioral phenotypes resembling mild human ARX mutations. Cereb. Cortex 25:2939–50
    [Google Scholar]
  98. 98.  Ventruti A, Kazdoba TM, Niu S, D'Arcangelo G 2011. Reelin deficiency causes specific defects in the molecular composition of the synapses in the adult brain. Neuroscience 189:32–42
    [Google Scholar]
  99. 99.  Chang BS 2015. Tubulinopathies and their brain malformation syndromes: every TUB on its own bottom. Epilepsy Curr 15:65–67
    [Google Scholar]
  100. 100.  Harding BN, Moccia A, Drunat S, Soukarieh O, Tubeuf H et al. 2016. Mutations in citron kinase cause recessive microlissencephaly with multinucleated neurons. Am. J. Hum. Genet. 99:511–20
    [Google Scholar]
  101. 101.  Juric-Sekhar G, Kapur RP, Glass IA, Murray ML, Parnell SE, Hevner RF 2011. Neuronal migration of disorders in microcephalic osteodysplastic primordial dwarfism type I/III. Acta Neuropathol 121:545–54
    [Google Scholar]
  102. 102.  Wang Y, Wu X, Du L, Zheng J, Deng S et al. 2018. Identification of compound heterozygous variants in the noncoding RNU4ATAC gene in a Chinese family with two successive foetuses with severe microcephaly. Hum. Genom. 12:3
    [Google Scholar]
  103. 103.  Dobyns WB, Kirkpatrick JB, Hittner HM, Roberts RM, Kretzer FL 1985. Syndromes with lissencephaly: II. Walker-Warburg and cerebro-oculo-muscular syndromes and a new syndrome with type II lissencephaly. Am. J. Med. Genet. 22:157–95
    [Google Scholar]
  104. 104.  Verrotti A, Spalice A, Ursitti F, Papetti L, Mariani R et al. 2010. New trends in neuronal migration disorders. Eur. J. Paediatr. Neurol. 14:1–12
    [Google Scholar]
  105. 105.  Ishigaki K, Ihara C, Mori-Yashimura M, Murakami T, Sato T et al. 2016. Japanese nationwide registry for Fukuyama congenital muscular dystrophy patients. Neuromuscul. Disord. 26:Suppl. 2 S164 (Abstr.)
    [Google Scholar]
  106. 106.  Kobayashi K, Kato R, Kondo-Iida E, Taniguchi-Ikeda M, Osawa M et al. 2017. Deep-intronic variant of fukutin in the most prevalent point mutation of Fukuyama congenital muscular dystrophy in Japan. J. Hum. Genet. 62:945–48
    [Google Scholar]
  107. 107.  Devisme L, Bouchet C, Gonzalès M, Alanio E, Bazin A et al. 2012. Cobblestone lissencephaly: neuropathological subtypes and correlations with genes of dystroglycanopathies. Brain 135:469–82
    [Google Scholar]
  108. 108.  Vuillaumier-Barrot S, Bouchet-Séraphin C, Chelbi M, Devisme L, Quentin S et al. 2012. Identification of mutations in TMEM5 and ISPD as a cause of severe cobblestone lissencephaly. Am. J. Hum. Genet. 91:1135–43
    [Google Scholar]
  109. 109.  Myshrall TD, Moore SA, Ostendorf AP, Satz JS, Kowalczyk T et al. 2012. Dystroglycan on radial glia end feet is required for pial basement membrane integrity and columnar organization of the developing cerebral cortex. J. Neuropathol. Exp. Neurol. 71:1047–63
    [Google Scholar]
  110. 110.  Radmanesh F, Caglayan AO, Silhavy JL, Yilmaz C, Cantagrel V et al. 2013. Mutations in LAMB1 cause cobblestone brain malformation without muscular or ocular abnormalities. Am. J. Hum. Genet. 92:468–74
    [Google Scholar]
  111. 111.  Radner S, Banos C, Bachay G, Li YN, Hunter DD et al. 2013. β2 and γ3 laminins are critical cortical basement membrane components: Ablation of Lamb2 and Lamc3 genes disrupts cortical lamination and produces dysplasia. Dev. Neurobiol. 73:209–29
    [Google Scholar]
  112. 112.  Bahi-Buisson N, Nectoux J, Girard B, Van Esch H, De Ravel T et al. 2010. Revisiting the phenotype associated with FOXG1 mutations: two novel cases of congenital Rett variant. Neurogenetics 11:241–49
    [Google Scholar]
  113. 113.  Duerinckx S, Abramowicz M 2018. The genetics of congenitally small brains. Semin. Cell Dev. Biol. 76:76–85
    [Google Scholar]
  114. 114.  Boland E, Clayton-Smith J, Woo VG, McKee S, Manson FD et al. 2007. Mapping of deletion and translocation breakpoints in 1q44 implicates the serine/threonine kinase AKT3 in postnatal microcephaly and agenesis of the corpus callosum. Am. J. Hum. Genet. 81:292–303
    [Google Scholar]
  115. 115.  Shiba N, Daza RA, Shaffer LG, Barkovich AJ, Dobyns WB, Hevner RF 2013. Neuropathology of brain and spinal malformations in a case of monosomy 1p36. Acta Neuropathol. Commun. 1:45
    [Google Scholar]
  116. 116.  Judkins AR, Martinez D, Ferreira P, Dobyns WB, Golden JA 2011. Polymicrogyria includes fusion of the molecular layer and decreased neuronal populations but normal cortical laminar organization. J. Neuropathol. Exp. Neurol. 70:438–43
    [Google Scholar]
  117. 117.  Jansen AC, Robitaille Y, Honavar M, Mullatti N, Leventer RJ et al. 2016. The histopathology of polymicrogyria: a series of 71 brain autopsy studies. Dev. Med. Child Neurol. 58:39–48
    [Google Scholar]
  118. 118.  Edwards TJ, Sherr EH, Barkovich AJ, Richards LJ 2014. Clinical, genetic and imaging findings identify new causes for corpus callosum development syndromes. Brain 137:1579–613
    [Google Scholar]
  119. 119.  Sotiriadis A, Makrydimas G 2012. Neurodevelopment after prenatal diagnosis of isolated agenesis of the corpus callosum: an integrative review. Am. J. Obstet. Gynecol. 206:e331–35
    [Google Scholar]
  120. 120.  Hevner RF, Shi L, Justice N, Hsueh Y, Sheng M et al. 2001. Tbr1 regulates differentiation of the preplate and layer 6. Neuron 29:353–66
    [Google Scholar]
  121. 121.  Donahoo AL, Richards LJ 2009. Understanding of callosal development through the use of transgenic mouse modes. Semin. Pediatr. Neurol. 16:127–42
    [Google Scholar]
  122. 122.  Chinn GA, Hirokawa KE, Chuang TM, Urbina C, Patel F et al. 2015. Agenesis of the corpus callosum due to defective glial wedge formation in Lhx2 mutant mice. Cereb. Cortex 25:2707–18
    [Google Scholar]
  123. 123.  O'Driscoll MC, Black GC, Clayton-Smith J, Sherr EH, Dobyns WB 2010. Identification of genomic loci contributing to agenesis of the corpus callosum. Am. J. Med. Genet. A 152A:2145–59
    [Google Scholar]
  124. 124.  Badano JL, Mitsuma N, Beales PL, Katsanis N 2006. The ciliopathies: an emerging class of the human genetic disorders. Annu. Rev. Genom. Hum. Genet. 7:125–48
    [Google Scholar]
  125. 125.  Alby C, Boutaud L, Bonniére M, Collardeau-Frachon S, Guibaud L et al. 2018. In utero ultrasound diagnosis of corpus callosum agenesis leading to the identification of orofaciodigital type 1 syndrome in female fetuses. Birth Defects Res 110:382–89
    [Google Scholar]
  126. 126.  Jouan L, Bencheikh BOA, Daoud H, Dionne-Laporte A, Dobrzeniecka S et al. 2016. Exome sequencing identified recessive CDK5RAP2 variants in patients with isolated agenesis of corpus callosum. Eur. J. Hum. Genet. 24:607–10
    [Google Scholar]
  127. 127.  Lee JH, Huynh M, Silhavy JL, Kim S, Dixon-Salazar T et al. 2012. De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly. Nat. Genet. 44:941–45
    [Google Scholar]
  128. 128.  Mirzaa G, Parry DA, Fry AE, Giamanco KA, Schwartzentruber J et al. 2014. De novo CCND2 mutations leading to stabilization of cyclin D2 cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome. Nat. Genet. 46:510–15
    [Google Scholar]
  129. 129.  D'Gama AM, Geng Y, Couto JA, Martin B, Boyle EA et al. 2015. Mammalian target of rapamycin pathway mutations cause hemimegalencephaly and focal cortical dysplasia. Ann. Neurol. 77:720–25
    [Google Scholar]
  130. 130.  Scheffer IE, Heron SE, Regan BM, Mandelstam S, Crompton DE et al. 2014. Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations. Ann. Neurol. 75:782–87
    [Google Scholar]
  131. 131.  Scerri T, Riseley JR, Gillies G, Pope K, Burgess R et al. 2015. Familiar cortical dysplasia type IIA caused by a germline mutation in DEPDC5. Ann. Clin. Transl. Neurol. 2:575–80
    [Google Scholar]
  132. 132.  Cen Z, Guo Y, Lou Y, Jiang B, Wang J, Feng J 2017. De novo mutation in DEPDC5 associated with unilateral pachygyria and intractable epilepsy. Seizure 50:1–3
    [Google Scholar]
  133. 133.  Ricos MG, Hodgson BL, Pippucci T, Saidin A, Ong YS et al. 2016. Mutations in the mammalian target of rapamycin pathway regulators NPRL2 and NPRL3 cause focal epilepsy. Ann. Neurol. 79:120–31
    [Google Scholar]
  134. 134.  Lim JS, Kim WI, Kang HC, Kim SH, Park AH et al. 2015. Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy. Nat. Med. 21:395–400
    [Google Scholar]
  135. 135.  Nakashima M, Saitsu H, Takei N, Tohyama J, Kato M et al. 2015. Somatic mutations in the MTOR gene cause focal cortical dysplasia type IIb. Ann. Neurol. 78:375–86
    [Google Scholar]
  136. 136.  Leventer RJ, Scerri T, Marsh AP, Pope K, Gillies G et al. 2015. Hemispheric cortical dysplasia secondary to a mosaic somatic mutation in MTOR. . Neurology 84:2029–32
    [Google Scholar]
  137. 137.  Mirzaa GM, Campbell CD, Solovieff N, Goold C, Jansen LA et al. 2016. Association of MTOR mutations with developmental brain disorders, including megalencephaly, focal cortical dysplasia, and pigmentary mosaicism. JAMA Neurol 73:836–45
    [Google Scholar]
  138. 138.  Sim JC, Scerri T, Fanjul-Fernández M, Riseley JR, Gillies G et al. 2016. Familiar cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3. Ann. . Neurol 79:132–37
    [Google Scholar]
  139. 139.  Mirzaa GM, Conti V, Timms AE, Smyser CD, Ahmed S et al. 2015. Characterisation of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next generation sequencing study. Lancet Neurol 14:1182–95
    [Google Scholar]
  140. 140.  Terrone G, Voisin N, Abdullah Alfaiz A, Cappuccio G, Vitiello G et al. 2016. De novo PIK3R2 variant causes polymicrogyria, corpus callosum hyperplasia and focal cortical dysplasia. Eur. J. Hum. Genet. 24:1359–62
    [Google Scholar]
  141. 141.  Shick V, Majores M, Engels G, Spitoni S, Koch A et al. 2006. Activation of Akt independent of PTEN and CTMP tumor-suppressor gene mutations in epilepsy-associated Taylor-type focal cortical dysplasia. Acta Neuropathol 112:715–25
    [Google Scholar]
  142. 142.  Crino PB, Nathanson KL, Henske EP 2006. The tuberous sclerosis complex. N. Engl. J. Med. 35:1345–56
    [Google Scholar]
  143. 143.  Lim JS, Gopalappa R, Kim SH, Ramakrishna S, Lee M et al. 2017. Somatic mutations in TSC1 and TSC2 cause focal cortical dysplasia. Am. J. Hum. Genet. 100:454–72
    [Google Scholar]
  144. 144.  Martin KR, Zhou W, Bowman MJ, Shih J, Au KS et al. 2017. The genomic landscape of tuberous sclerosis complex. Nat. Commun. 8:15816
    [Google Scholar]
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