Lissencephaly

A smooth brain malformation of the CEREBRAL CORTEX resulting from the abnormal location of developing neurons during corticogenesis. It is characterized by an absence of normal convoluted indentations on the surface of the brain (agyria), or fewer and shallower indentations (pachygryia). There is a reduced number of cortical layers, typically 4 instead of 6, resulting in a thickened cortex, and reduced cerebral white matter that is a reversal of the normal ratio of cerebral white matter to cortex.

Also Known As:

Networked: 236 relevant articles (0 outcomes, 14 trials/studies)

Disease Context: Research Results

Related Diseases

1.	Lissencephaly
2.	Polymicrogyria
3.	Malformations of Cortical Development
4.	Epilepsy (Aura)
5.	Tuberous Sclerosis (Bourneville's Disease)

Experts

1.	Wynshaw-Boris, Anthony: 10 articles (03/2013 - 06/2003)
2.	Hirotsune, Shinji: 9 articles (01/2022 - 08/2003)
3.	Chelly, Jamel: 9 articles (01/2018 - 01/2007)
4.	Dobyns, William B: 8 articles (10/2019 - 02/2004)
5.	Das, Soma: 4 articles (05/2021 - 02/2004)
6.	Guerrini, Renzo: 4 articles (01/2021 - 02/2004)
7.	Gleeson, Joseph G: 4 articles (10/2019 - 06/2004)
8.	Keays, David A: 4 articles (01/2017 - 01/2007)
9.	Tian, Guoling: 4 articles (11/2016 - 01/2007)
10.	Kato, Mitsuhiro: 4 articles (01/2016 - 02/2004)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Lissencephaly:

1.	DNA (Deoxyribonucleic Acid)IBA 11/01/1993 - "Appropriate studies include computed tomography or magnetic resonance imaging (sometimes both), chromosome analysis, DNA analysis of the lissencephaly region on chromosome 17, electroencephalography and sometimes metabolic studies." 11/01/2018 - "We collected DNA from 756 children with lissencephaly over 30 years. " 06/01/2008 - "We initially performed DNA sequencing in 45 patients with isolated lissencephaly with a p>a gradient, in whom FISH had revealed normal results. " 08/01/1991 - "The DNA of the patient showed deletions of markers YNZ22.1 and YNH37.3. This is the first report of a case of ILS (with grade 3 lissencephaly) with a submicroscopic deletion. " 09/01/1991 - "DNA analysis in patients with lissencephaly type I and other cortical dysplasias."
2.	Proteins (Proteins, Gene)FDA Link 01/01/2021 - "Variants in CEP85L, encoding a protein involved in the regulation of neuronal migration, have been recently described as causative of lissencephaly with a posterior-prevalent involvement of the cerebral cortex and an autosomal dominant pattern of inheritance. " 11/04/2019 - "Deficiency of the LIS1 protein causes lissencephaly, a brain developmental disorder. " 01/01/2018 - "C-terminal directed mutations also impair plasticity possibly through altered interactions with lissencephaly protein 1 (LIS1) and nuclear distribution protein nudE-like 1 (NDEL1), thereby affecting developmental processes such as dendritic structure and spine maturation. " 01/01/2018 - "Zic1, Zic2, Zic3, and Zic5 proteins are required for the development of neural crest derivatives, including the meningeal membrane and facial bones, and deficiency of these proteins causes cortical lamination defects resembling those in type II lissencephaly. " 10/31/2017 - "We focused on the poorly studied WDR47 protein sharing structural homology with LIS1, which causes lissencephaly. "
3.	TubulinIBA 11/01/2020 - "A recurrent mutation (R402H) in the α-tubulin gene TUBA1A is known to cause lissencephaly with cerebellar and striatal phenotypes. " 01/01/2016 - "To overcome these limitations, we generated induced pluripotent stem cells (iPSCs) from the umbilical cord and peripheral blood of two lissencephaly patients with different clinical severities carrying alpha tubulin (TUBA1A) missense mutations (Patient A, p.N329S; Patient B, p.R264C). " 02/01/2014 - "Gene mutation of tubulin alpha-1A (TUBA1A), a critical component of microtubules of the cytoskeleton, impairs neural migration and causes lissencephaly (LIS). " 03/01/2008 - "A pachygyria-causing alpha-tubulin mutation results in inefficient cycling with CCT and a deficient interaction with TBCB." 01/12/2007 - "Mutations in alpha-tubulin cause abnormal neuronal migration in mice and lissencephaly in humans."
4.	Dyneins (Dynein)IBA 02/03/2003 - "LIS1, the product of a causal gene for human lissencephaly (smooth brain), has also been implicated in dynein function based on studies in fungi and more recent studies in higher eukaryotic systems (for review see Gupta et al., 2002). " 01/01/2023 - "Lis1 (also known as PAFAH1B1) is a conserved dynein regulator that is mutated in the neurodevelopmental disease lissencephaly. " 01/01/2022 - "Depletion of LIS1, famous for linking dynein deregulation to lissencephaly (smooth brain), in adult mice leads to severe neurological phenotypes, demonstrating post-developmental roles. " 01/01/2019 - "TUBA1A mutations identified in lissencephaly patients dominantly disrupt neuronal migration and impair dynein activity." 04/01/2008 - "Dynein inhibition resulted in similar defects in both nucleus-centrosome (N-C) coupling and neuronal migration, suggesting that defects in this coupling may contribute to migration defects in lissencephaly. "
5.	Cytoplasmic DyneinsIBA 02/23/2010 - "The type I lissencephaly gene product LIS1, a key regulator of cytoplasmic dynein, is critical for cell proliferation, survival, and neuronal migration. " 02/03/2010 - "The LIS1 (or PAFAH1B1) gene was identified as the gene mutated in lissencephaly patients, and was found to regulate cytoplasmic dynein function and localization. " 05/01/2008 - "[Molecular mechanism of lissencephaly: how LIS1 regulates cytoplasmic dynein]." 04/01/2008 - "[Molecular mechanism of lissencephaly--how LIS1 and NDEL1 regulate cytoplasmic dynein?]." 10/01/2007 - "The identification of LIS1 as the first lissencephaly gene, and the first gene required for neuronal migration has revealed the importance of the regulation of cytoplasmic dynein in the control of neuronal migration by modulating nuclear migration in a pathway conserved in virtually all eukaryotes."
6.	Platelet Activating FactorIBA 12/01/1997 - "Previous studies have shown that LIS1, the defective gene found in patients with lissencephaly, is a subunit of the platelet-activating factor acetylhydrolase. " 09/01/2015 - "One of the human genes responsible for lissencephaly is the platelet-activating factor acetylhydrolase 1b gene (PAFAH1B; also known as LIS1) located on 17p13.3. Patients with heterozygous deletion of this chromosomal region exhibit lissencephaly. " 01/01/2006 - "In order to test the hypothesis that these features may be related with genes that regulate neuronal migration, we analyzed two genomic regions: the lissencephaly critical region (chromosome 17p) encompassing the LIS1 gene and which is involved in human lissencephaly; and the genes related to the platelet-activating-factor, functionally related to LIS1, in 52 schizophrenic patients, 36 bipolar I patients and 65 normal control subjects. " 05/01/2001 - "Furthermore, abnormal prenatal platelet activating factor (PAF) signalling may result in lissencephaly, a disorder of neuronal migration. " 08/01/1998 - "Heterozygous mutation or deletion of the beta subunit of platelet-activating factor acetylhydrolase (PAFAH1B1, also known as LIS1) in humans is associated with type I lissencephaly, a severe developmental brain disorder thought to result from abnormal neuronal migration. "
7.	Technetium Tc 99m Exametazime (Ceretec)FDA Link 01/01/1991 - "Infantile spasm induced by hemispheric pachygyria ultrasound, MRIand Tc-99m HMPAO SPECT." 03/01/1997 - "Cerebral perfusion was investigated in three patients with agyria-pachygyria by using 99mTc-HMPAO SPECT in order to study the distribution of blood flow. " 03/01/1997 - "Agyria-pachygyria: cerebral perfusion studies by 99mTc-HMPAO SPECT [corrected]."
8.	KinesinsIBA 08/21/2014 - "We found potentially causal mutations in the candidate genes DYNC1H1, KIF5C, and other kinesin genes in persons with pachygyria. " 09/01/2020 - "Recent studies have established a relationship between lissencephaly and pathogenic variants in genes involved in the kinesin/tubulin pathways, as the KIF5C gene. "
9.	Coloring Agents (Dyes)IBA 10/01/1977 - "A case of lissencephaly (agyria) is reported in which the Golgi stain was used to study the fronto-parietal cortex. " 01/01/1999 - "Macroscopic morphometric analysis was performed in the brains of the microgyria-pachygyria type using the coronal whole brain sections through the mammillary bodies stained with Klüver-Barerra (KB) stain, and compared with the brains of four cases of the Fukuyama type congenital muscular dystrophy (FCMD), two cases of lissencephaly, and nine cases of non-neural diseases as controls. "
10.	CollagenIBA 02/01/1997 - "We found that the pattern of collagen subtypes I, III and VI was not altered in type II lissencephaly brains when compared to normal controls. " 11/01/2015 - "The most severe form of dysplastic changes was characterized by marked irregularity of the cerebellar cortex similar to that in lissencephaly type II. Thus, prenatal vitamin C deficiency represents a novel animal model to study the effects of collagen synthesis on development of breaches in the pial basement membrane, disordered migration of neurons, dysplasia of cerebellar cortex, and the pathogenesis of lissencephaly. "

Therapies and Procedures

1.	Telescopes 03/01/2009 - "We describe a 12-year old girl with developmental delay, hearing loss, cortical micro- and pachygyria, and a cystic craniopharyngioma; her ocular features include unilateral Duane syndrome, monocular nystagmus under binocular conditions, and a patterned hyperpigmentation of the retinal pigment epithelium. "
2.	Therapeutics 04/01/2008 - "Coordinated regulation of cytoplasmic dynein and microtubule organization is vital for proper cell division and cell positioning, which is an important research problem for understanding of corticogenesis and promoting the development of new therapies for lissencephaly and related disorders."
3.	Sutures (Suture) 01/01/1958 - "[Incomplete suture of corpus callosum in a case of lissencephalia of the two hemispheres; organogenetic relations between these two diseases]."
4.	Ligation 07/01/2009 - "We studied a series of 83 patients with ILS, SBH or pachygyria, in whom no abnormalities of the LIS1 or DCX genes had been identified, for intragenic deletions and duplications by multiplex ligation-dependent probe amplification (MLPA). "
5.	Intraperitoneal Injections 12/01/1983 - "Lissencephaly was produced by a single intraperitoneal injection of 15 mg methylazoxymethanol acetate to pregnant animals. "