Spectrum of cortical malformation caused by abnormal transmantle neuronal migration
Includes agyria, pachygyria, and subcortical band heterotopia
Most updated classification is based on combination of involved stage of neuronal migration and genetic information
Tubulinopathies: Secondary to mutations coding microtubule-associated proteins (MAPs): DCX, LIS1, or tubulins (TUBA genes)
Includes classic (a.k.a. type 1) lissencephalies: Thick, 4-layer cortex with cell-sparse zone
Variant lissencephalies: ARX and RELN mutations
Slightly less thick cortex with no cell-sparse zone
Abnormalities of neuronal proliferation (microlissencephaly, microcephaly with simplified gyral pattern, megalencephalies) and dystroglycanopathies (cobblestone malformations, previously type II lissencephaly) are described in separate categories
However, there is phenotypic and genetic overlap with microcephaly and tubulin mutations
IMAGING
General Features
CT Findings
MR Findings
Ultrasonographic Findings
Nuclear Medicine Findings
Imaging Recommendations
DIFFERENTIAL DIAGNOSIS
PATHOLOGY
General Features
Microscopic Features
CLINICAL ISSUES
Presentation
Demographics
Treatment
DIAGNOSTIC CHECKLIST
Consider
Image Interpretation Pearls
Reporting Tips
Selected References
Bott CJ et al: Nestin selectively facilitates the phosphorylation of the Lissencephaly-linked protein doublecortin (DCX) by cdk5/p35 to regulate growth cone morphology and Sema3a sensitivity in developing neurons. J Neurosci. 40(19): 370-40, 2020
Ffrench-Constant S et al: Fetal and neonatal MRI features of ARX-related lissencephaly presenting with neonatal refractory seizure disorder. Quant Imaging Med Surg. 9(11):1767-72, 2019
Desikan RS et al: Malformations of cortical development. Ann Neurol. 80(6):797-810, 2016
Barkovich AJ et al: Malformations of cortical development and epilepsy. Cold Spring Harb Perspect Med. 5(5):a022392, 2015
Kato M: Genotype-phenotype correlation in neuronal migration disorders and cortical dysplasias. Front Neurosci. 9:181, 2015
Fry AE et al: The genetics of lissencephaly. Am J Med Genet C Semin Med Genet. 166C(2):198-210, 2014
Bahi-Buisson N et al: New insights into genotype-phenotype correlations for the doublecortin-related lissencephaly spectrum. Brain. 136(Pt 1):223-44, 2013
Barkovich AJ et al: Pediatric Neuroimaging. 5th ed. Philadelphia: Lippincott Williams & Wilkins. 419-429, 2012
Barkovich AJ et al: A developmental and genetic classification for malformations of cortical development: update 2012. Brain. 135(Pt 5):1348-69, 2012
Toba S et al: A unique role of dynein and nud family proteins in corticogenesis. Neuropathology. 32(4):432-9, 2012
Alkuraya FS et al: Human mutations in NDE1 cause extreme microcephaly with lissencephaly [corrected]. Am J Hum Genet. 2011 May 13;88(5):536-47. Epub 2011 Apr 28. Erratum in: Am J Hum Genet. 88(5):677, 2011
Jansen AC et al: TUBA1A mutations: from isolated lissencephaly to familial polymicrogyria. Neurology. 76(11):988-92, 2011
Abdel Razek AA et al: Disorders of cortical formation: MR imaging features. AJNR Am J Neuroradiol. 30(1):4-11, 2009
Reiner O et al: Lissencephaly 1 linking to multiple diseases: mental retardation, neurodegeneration, schizophrenia, male sterility, and more. Neuromolecular Med. 8(4):547-65, 2006
Pfund Z et al: Lissencephaly: fetal pattern of glucose metabolism on positron emission tomography? Neurology. 55(11):1683-8, 2000
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References
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Tables
KEY FACTS
Terminology
Imaging
Top Differential Diagnoses
Pathology
Clinical Issues
TERMINOLOGY
Definitions
Spectrum of cortical malformation caused by abnormal transmantle neuronal migration
Includes agyria, pachygyria, and subcortical band heterotopia
Most updated classification is based on combination of involved stage of neuronal migration and genetic information
Tubulinopathies: Secondary to mutations coding microtubule-associated proteins (MAPs): DCX, LIS1, or tubulins (TUBA genes)
Includes classic (a.k.a. type 1) lissencephalies: Thick, 4-layer cortex with cell-sparse zone
Variant lissencephalies: ARX and RELN mutations
Slightly less thick cortex with no cell-sparse zone
Abnormalities of neuronal proliferation (microlissencephaly, microcephaly with simplified gyral pattern, megalencephalies) and dystroglycanopathies (cobblestone malformations, previously type II lissencephaly) are described in separate categories
However, there is phenotypic and genetic overlap with microcephaly and tubulin mutations
IMAGING
General Features
CT Findings
MR Findings
Ultrasonographic Findings
Nuclear Medicine Findings
Imaging Recommendations
DIFFERENTIAL DIAGNOSIS
PATHOLOGY
General Features
Microscopic Features
CLINICAL ISSUES
Presentation
Demographics
Treatment
DIAGNOSTIC CHECKLIST
Consider
Image Interpretation Pearls
Reporting Tips
Selected References
Bott CJ et al: Nestin selectively facilitates the phosphorylation of the Lissencephaly-linked protein doublecortin (DCX) by cdk5/p35 to regulate growth cone morphology and Sema3a sensitivity in developing neurons. J Neurosci. 40(19): 370-40, 2020
Ffrench-Constant S et al: Fetal and neonatal MRI features of ARX-related lissencephaly presenting with neonatal refractory seizure disorder. Quant Imaging Med Surg. 9(11):1767-72, 2019
Desikan RS et al: Malformations of cortical development. Ann Neurol. 80(6):797-810, 2016
Barkovich AJ et al: Malformations of cortical development and epilepsy. Cold Spring Harb Perspect Med. 5(5):a022392, 2015
Kato M: Genotype-phenotype correlation in neuronal migration disorders and cortical dysplasias. Front Neurosci. 9:181, 2015
Fry AE et al: The genetics of lissencephaly. Am J Med Genet C Semin Med Genet. 166C(2):198-210, 2014
Bahi-Buisson N et al: New insights into genotype-phenotype correlations for the doublecortin-related lissencephaly spectrum. Brain. 136(Pt 1):223-44, 2013
Barkovich AJ et al: Pediatric Neuroimaging. 5th ed. Philadelphia: Lippincott Williams & Wilkins. 419-429, 2012
Barkovich AJ et al: A developmental and genetic classification for malformations of cortical development: update 2012. Brain. 135(Pt 5):1348-69, 2012
Toba S et al: A unique role of dynein and nud family proteins in corticogenesis. Neuropathology. 32(4):432-9, 2012
Alkuraya FS et al: Human mutations in NDE1 cause extreme microcephaly with lissencephaly [corrected]. Am J Hum Genet. 2011 May 13;88(5):536-47. Epub 2011 Apr 28. Erratum in: Am J Hum Genet. 88(5):677, 2011
Jansen AC et al: TUBA1A mutations: from isolated lissencephaly to familial polymicrogyria. Neurology. 76(11):988-92, 2011
Abdel Razek AA et al: Disorders of cortical formation: MR imaging features. AJNR Am J Neuroradiol. 30(1):4-11, 2009
Reiner O et al: Lissencephaly 1 linking to multiple diseases: mental retardation, neurodegeneration, schizophrenia, male sterility, and more. Neuromolecular Med. 8(4):547-65, 2006
Pfund Z et al: Lissencephaly: fetal pattern of glucose metabolism on positron emission tomography? Neurology. 55(11):1683-8, 2000
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