MCID: LSS002
MIFTS: 49

Lissencephaly

Categories: Rare diseases, Genetic diseases, Fetal diseases, Neuronal diseases, Muscle diseases, Skin diseases, Cardiovascular diseases

Aliases & Classifications for Lissencephaly

Summaries for Lissencephaly

NIH Rare Diseases : 49 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 48471Disease definitionThe term lissencephaly covers a group of rare malformations sharing the common feature of anomalies in the appearance of brain convolutions (characterised by simplification or absence of folding) associated with abnormal organisation of the cortical layers as a result of neuronal migration defects during embryogenesis.EpidemiologyThe incidence of all forms of type I lissencephaly is around 1 in 100,000 births.Clinical descriptionChildren with lissencephaly have feeding and swallowing problems, muscle tone anomalies (early hypotonia and subsequently limb hypertonia), seizures (in particular, infantile spasms) and severe psychomotor retardation. Multiple forms of lissencephaly have been described and their current classification is based on the associated malformations and underlying aetiology. Two large groups can be distinguished: classical lissencephaly (and its variants) and cobblestone lissencephaly. In classical lissencephaly (or type I), the cortex appears thickened, with four more or less disorganised layers rather than six normal layers. In the variants of classical lissencephaly, extra-cortical anomalies are also present (total or subtotal agenesis of the corpus callosum and/or cerebellar hypoplasia). The classical lissencephalies and the variant forms can be further divided into several subgroups. Four forms can be distinguished on the basis of their genetic aetiology: anomalies in the LIS1 gene (isolated lissencephaly and Miller-Dieker syndrome, see these terms), anomalies in the TUBA3 and DCX genes, and lissencephalies caused by mutations in the ARX gene (X-linked lissencephaly with agenesis of the corpus callosum (XLAG) syndrome; see this term). In addition to these four entities, isolated lissencephalies without a known genetic defect, lissencephalies with severe microcephaly (microlissencephaly) and lissencephalies associated with polymalformative syndromes are also included in the group of classical lissencephalies. Cobblestone lissencephaly (formally referred to as type II) is present in three entities: the Walker-Warburg, Fukuyama and MEB (Muscle-Eye-Brain) syndromes (see these terms). It is characterised by global disorganisation of cerebral organogenesis with an uneven cortical surface (with a pebbled or cobblestone appearance). Microscopic examination reveals total disorganisation of the cortex and the absence of any distinguishable layers.Management and treatmentManagement is symptomatic only (swallowing problems require adapted feeding to prevent food aspiration, articular and respiratory physiotherapy to prevent orthopaedic problems resulting from hyptonia, and treatment of gastrooesophageal reflux). The epilepsy is often resistant to treatment.PrognosisThe encephalopathy associated with lissencephaly is often very severe and affected children are completely dependent on their carer.Visit the Orphanet disease page for more resources. Last updated: 6/22/2007

MalaCards based summary : Lissencephaly is related to lissencephaly 1 and lissencephaly, x-linked, 1. An important gene associated with Lissencephaly is PAFAH1B1 (Platelet Activating Factor Acetylhydrolase 1b Regulatory Subunit 1), and among its related pathways/superpathways are Reelin Pathway (Cajal-Retzius cells) and Guidance Cues and Growth Cone Motility. Affiliated tissues include brain, cortex and eye, and related phenotypes are cellular and behavior/neurological

Disease Ontology : 12 A congenital nervous system abnormality characterized by the absence of folds in the cerebral cortex and caused_by defective neuronal migration during the 12th to 24th weeks of gestation.

NINDS : 50 Lissencephaly, which literally means "smooth brain," is a rare, gene-linked brain malformation characterized by the absence of normal convolutions (folds) in the cerebral cortex and an abnormally small head (microcephaly). In the usual condition of lissencephaly, children usually have a normal sized head at birth.  In children with reduced head size at birth, the condition microlissencephaly is typically diagnosed.  Lissencephaly is caused by defective neuronal migration during embryonic development,  the process in which nerve cells move from their place of origin to their permanent location within the cerebral cortex gray matter. Symptoms of the disorder may include unusual facial appearance, difficulty swallowing, failure to thrive, muscle spasms, seizures, and severe psychomotor retardation. Hands, fingers, or toes may be deformed. Lissencephaly may be associated with other diseases including isolated lissencephaly sequence, Miller-Dieker syndrome, and Walker-Warburg syndrome.  Sometimes it can be difficult to distinguish between these  conditions clinically so consultation with national experts is recommended to help ensure correct diagnosis and possible molecular testing.

Wikipedia : 72 Lissencephaly is a set of rare brain disorders where the whole or parts of the surface of the brain... more...

Related Diseases for Lissencephaly

Diseases in the Lissencephaly family:

Lissencephaly 2 Lissencephaly 1
Lissencephaly 3 Lissencephaly 4
Lissencephaly 5 Lissencephaly 8

Diseases related to Lissencephaly via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 149)
# Related Disease Score Top Affiliating Genes
1 lissencephaly 1 34.2 DCX PAFAH1B1 RELN
2 lissencephaly, x-linked, 1 34.1 ARX DCX PAFAH1B1
3 miller-dieker lissencephaly syndrome 33.4 NDE1 PAFAH1B1 TUBA1A YWHAE
4 band heterotopia 32.1 DCX PAFAH1B1
5 muscular dystrophy-dystroglycanopathy , type a, 1 31.9 FKRP FKTN
6 lissencephaly with cerebellar hypoplasia 31.8 ARX CDK5 DCX LRP8 PAFAH1B1 RELN
7 pachygyria 31.0 CDK5 DCX KATNB1 PAFAH1B1 RELN TMTC3
8 walker-warburg syndrome 30.9 DAG1 FKRP FKTN TMTC3
9 subcortical band heterotopia 30.8 DCX PAFAH1B1
10 neuronal migration disorders 30.8 ARX DCX PAFAH1B1 RELN VLDLR YWHAE
11 muscular dystrophy-dystroglycanopathy , type a, 4 30.7 DAG1 FKRP FKTN
12 cerebellar hypoplasia 30.5 DCX PAFAH1B1 RELN VLDLR
13 muscular dystrophy, congenital, lmna-related 29.6 DAG1 FKRP FKTN
14 periventricular nodular heterotopia 29.5 DCX PAFAH1B1 RELN TMTC3 TUBA1A
15 lissencephaly 2 12.4
16 x-linked lissencephaly with abnormal genitalia 12.4
17 lissencephaly, x-linked, 2 12.4
18 lissencephaly 4 12.2
19 lissencephaly 5 12.2
20 lissencephaly 6 with microcephaly 12.2
21 lissencephaly 3 12.2
22 lissencephaly 7 with cerebellar hypoplasia 12.1
23 lissencephaly 8 12.1
24 mental retardation, autosomal recessive 34, with variant lissencephaly 12.1
25 lis1-associated lissencephaly/subcortical band heterotopia 12.0
26 lissencephaly type iii and bone dysplasia 11.8
27 lissencephaly, familial, with cleft palate and cerebellar hypoplasia 11.8
28 isolated lissencephaly type 1 without known genetic defects 11.8
29 lissencephaly type 3-familial fetal akinesia sequence syndrome 11.8
30 lissencephaly with cerebellar hypoplasia type f 11.8
31 lissencephaly with cerebellar hypoplasia type e 11.8
32 lissencephaly with cerebellar hypoplasia type b 11.8
33 lissencephaly with cerebellar hypoplasia type a 11.8
34 lissencephaly with cerebellar hypoplasia type d 11.8
35 lissencephaly with cerebellar hypoplasia type c 11.8
36 neu-laxova syndrome 1 11.2
37 cortical dysplasia, complex, with other brain malformations 7 11.1
38 colpocephaly 11.1
39 baraitser-winter syndrome 1 10.9
40 muscular dystrophy-dystroglycanopathy , type a, 10 10.9
41 microcephaly 17, primary, autosomal recessive 10.9
42 chromosome xq26.3 duplication syndrome 10.8
43 chromosome 17p13.1 deletion syndrome 10.8
44 congenital muscular alpha-dystroglycanopathy with brain and eye anomalies 10.8
45 massa casaer ceulemans syndrome 10.8
46 spondylometaphyseal dysplasia, sedaghatian type 10.7
47 muscular dystrophy-dystroglycanopathy , type a, 3 10.7
48 corpus callosum, agenesis of, with abnormal genitalia 10.7
49 mental retardation, x-linked, with or without seizures, arx-related 10.7
50 galloway-mowat syndrome 2, x-linked 10.7

Graphical network of the top 20 diseases related to Lissencephaly:



Diseases related to Lissencephaly

Symptoms & Phenotypes for Lissencephaly

MGI Mouse Phenotypes related to Lissencephaly:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.1 ARX CRADD DAG1 FKRP FKTN KATNB1
2 behavior/neurological MP:0005386 10.06 ARX CDK5 DAG1 DCX FKRP FKTN
3 growth/size/body region MP:0005378 9.93 ARX DAG1 DCX FKRP FKTN KATNB1
4 mortality/aging MP:0010768 9.8 ARX CDK5 CRADD DAG1 DCX FKRP
5 nervous system MP:0003631 9.47 ARX CDK5 DAG1 DCX FKRP FKTN

Drugs & Therapeutics for Lissencephaly

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Clinical-genetic Investigations in Children With Early Infantile Epilepsies Completed NCT01357707
2 Human Epilepsy Genetics--Neuronal Migration Disorders Study Recruiting NCT00041600
3 Congenital Muscle Disease Study of Patient and Family Reported Medical Information Recruiting NCT01403402

Search NIH Clinical Center for Lissencephaly

Cochrane evidence based reviews: lissencephaly

Genetic Tests for Lissencephaly

Genetic tests related to Lissencephaly:

# Genetic test Affiliating Genes
1 Lissencephaly 28

Anatomical Context for Lissencephaly

MalaCards organs/tissues related to Lissencephaly:

38
Brain, Cortex, Eye, Testes, Cerebellum, T Cells, Hypothalamus

Publications for Lissencephaly

Articles related to Lissencephaly:

(show top 50) (show all 341)
# Title Authors Year
1
A unique case of lissencephaly with Crouzon syndrome heterozygous for FGFR2 mutation. ( 29067506 )
2018
2
A novel recurrent LIS1 splice site mutation in classic lissencephaly. ( 27891766 )
2017
3
An in vitro model of lissencephaly: expanding the role of DCX during neurogenesis. ( 28924182 )
2017
4
A Neonate with X-linked Lissencephaly with Ambiguous Genitalia. ( 28553390 )
2017
5
Human iPSC-Derived Cerebral Organoids Model Cellular Features of Lissencephaly and Reveal Prolonged Mitosis of Outer Radial Glia. ( 28111201 )
2017
6
Lissencephaly in a Pekingese. ( 28819088 )
2017
7
Homozygous null variant in CRADD, encoding an adaptor protein that mediates apoptosis, is associated with lissencephaly. ( 28686357 )
2017
8
In utero MR imaging in fetuses at high risk of lissencephaly. ( 28134568 )
2017
9
Lissencephaly-pachygyria Masquerading as Leukodystrophy on Magnetic Resonance Imaging Brain. ( 28904573 )
2017
10
X-Linked Lissencephaly With Absent Corpus Callosum and Abnormal Genitalia: An Evolving Multisystem Syndrome With Severe Congenital Intestinal Diarrhea Disease. ( 29152528 )
2017
11
Lissencephaly: Expanded imaging and clinical classification. ( 28440899 )
2017
12
EP02.04: Prenatal ultrasound diagnosis of lissencephaly in the second trimester of gestation. ( 27644224 )
2016
13
Biallelic Mutations in TMTC3, Encoding a Transmembrane and TPR-Containing Protein, Lead to Cobblestone Lissencephaly. ( 27773428 )
2016
14
A patient with lissencephaly, developmental delay, and infantile spasms, due to de novo heterozygous mutation of KIF2A. ( 27896282 )
2016
15
Prenatal diagnosis of lissencephaly: A case report. ( 26964389 )
2016
16
In vitro characterization of neurite extension using induced pluripotent stem cells derived from lissencephaly patients with TUBA1A missense mutations. ( 27431206 )
2016
17
Recurrent KIF2A mutations are responsible for classic lissencephaly. ( 27747449 )
2016
18
Visual Impairment Due to Lissencephaly. ( 27928411 )
2016
19
Lissencephaly with agenesis of corpus callosum: A rare anomaly. ( 28050101 )
2016
20
Lissencephaly in an adult Australian Kelpie. ( 27021891 )
2016
21
A novel DCX missense mutation in a family with X-linked lissencephaly and subcortical band heterotopia syndrome inherited from a low-level somatic mosaic mother: Genetic and functional studies. ( 27292316 )
2016
22
The syndrome dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly and lissencephaly (DREAM-PL): Report of two additional patients. ( 27480277 )
2016
23
Prenatal Diagnosis of Lissencephaly Type 2 using Three-dimensional Ultrasound and Fetal MRI: Case Report and Review of the Literature. ( 27088705 )
2016
24
Mutations in CRADD Result in Reduced Caspase-2-Mediated Neuronal Apoptosis and Cause Megalencephaly with a Rare Lissencephaly Variant. ( 27773430 )
2016
25
Clinical Images: Postterm Newborn with Lissencephaly Presented with Seizure: Case Report and Review of Literature. ( 26130973 )
2015
26
Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with a loss-of-function mutation in CDK5. ( 25560765 )
2015
27
CHCHD2 is down-regulated in neuronal cells differentiated from iPS cells derived from patients with lissencephaly. ( 26188257 )
2015
28
Response to Correspondence on "Lissencephaly With Brainstem and Cerebellar Hypoplasia and Congenital Cataracts". ( 25805803 )
2015
29
Prenatal imaging diagnosis of cobblestone lissencephaly associated with Walker Warburg syndrome based on a specific sonographic pattern. ( 26315758 )
2015
30
A de novo microdeletion involving PAFAH1B (LIS1) related to lissencephaly phenotype. ( 26958590 )
2015
31
Watery diarrhea-hypopotassemia-acidosis syndrome like diarrhea in a case with X-linked lissencephaly with abnormal genitalia. ( 26129807 )
2015
32
Characterization of intragenic tandem duplication in the PAFAH1B1 gene leading to isolated lissencephaly sequence. ( 26523152 )
2015
33
LIS1-associated classic lissencephaly: A retrospective, multicenter survey of the epileptogenic phenotype and response to antiepileptic drugs. ( 26494205 )
2015
34
Type 1 lissencephaly and multiple afebrile seizures in a 2-month-old baby. ( 26167213 )
2015
35
Novel DCX mutation-caused lissencephaly in a boy and very mild heterotopia in his mother. ( 25868952 )
2015
36
A case of lissencephaly in a 5-month-old infant. ( 25612753 )
2015
37
A case of TUBA1A mutation presenting with lissencephaly and Hirschsprung disease. ( 23528852 )
2014
38
Lissencephaly with subcortical band heterotopia in an Indian family. ( 24493317 )
2014
39
Vitamin C Depletion in Prenatal Guinea Pigs as a Model of Lissencephaly Type II. ( 25487414 )
2014
40
The genetics of lissencephaly. ( 24862549 )
2014
41
DTI tractography of lissencephaly caused by TUBA1A mutation. ( 24510153 )
2014
42
miRNA-based buffering of the cobblestone-lissencephaly-associated extracellular matrix receptor dystroglycan via its alternative 3'-UTR. ( 25232965 )
2014
43
Lissencephaly presenting with congenital hypothyroidism. ( 23751382 )
2013
44
Post-natal treatment by a blood-brain-barrier permeable calpain inhibitor, SNJ1945 rescued defective function in lissencephaly. ( 23390575 )
2013
45
Identification of DCX gene mutation in lissencephaly spectrum with subcortical band heterotopia using whole exome sequencing. ( 23583063 )
2013
46
New insights into genotype-phenotype correlations for the doublecortin-related lissencephaly spectrum. ( 23365099 )
2013
47
Prenatal diagnosis of ring chromosome 2 with lissencephaly and 2p25.3 and 2q37.3 microdeletions detected using array comparative genomic hybridization. ( 23403238 )
2013
48
A case of schizophrenia accompanied by lissencephaly. ( 24247873 )
2013
49
Hereditary lissencephaly and cerebellar hypoplasia in Churra lambs. ( 23938146 )
2013
50
A novel inverted 17p13.3 microduplication disrupting PAFAH1B1 (LIS1) in a girl with syndromic lissencephaly. ( 23633430 )
2013

Variations for Lissencephaly

ClinVar genetic disease variations for Lissencephaly:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 NBN NM_002485.4(NBN): c.657_661delACAAA (p.Lys219Asnfs) deletion Pathogenic,risk factor rs587776650 GRCh37 Chromosome 8, 90983442: 90983446

Copy number variations for Lissencephaly from CNVD:

7
# CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 32413 12 36500000 66000000 Copy number TUBA1A Lissencephaly
2 225566 7 47600000 107200000 Copy number RELN Lissencephaly

Expression for Lissencephaly

Search GEO for disease gene expression data for Lissencephaly.

Pathways for Lissencephaly

GO Terms for Lissencephaly

Cellular components related to Lissencephaly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 neuronal cell body GO:0043025 9.78 CDK5 KATNB1 LRP8 PAFAH1B1
2 axon GO:0030424 9.65 CDK5 KATNB1 LRP8 PAFAH1B1 YWHAE
3 growth cone GO:0030426 9.61 CDK5 KATNB1 PAFAH1B1
4 cytoskeleton GO:0005856 9.56 CDK5 DAG1 DCX KATNB1 NDE1 NUDC
5 kinesin complex GO:0005871 9.54 NDE1 PAFAH1B1 YWHAE
6 dystrophin-associated glycoprotein complex GO:0016010 9.4 DAG1 FKRP
7 microtubule associated complex GO:0005875 9.33 DCX LRP8 PAFAH1B1
8 central region of growth cone GO:0090724 9.32 PAFAH1B1 YWHAE
9 microtubule GO:0005874 9.17 CDK5 DCX KATNB1 NDE1 NUDC PAFAH1B1
10 cytosol GO:0005829 10.2 CDK5 CRADD DAG1 DCX FKRP KATNB1

Biological processes related to Lissencephaly according to GeneCards Suite gene sharing:

(show all 35)
# Name GO ID Score Top Affiliating Genes
1 cell division GO:0051301 9.93 CDK5 KATNB1 NDE1 NUDC PAFAH1B1 TUBA1A
2 nervous system development GO:0007399 9.91 ARX CDK5 DCX FKTN NDE1 PAFAH1B1
3 cell migration GO:0016477 9.87 CDK5 NDE1 PAFAH1B1 RELN
4 G2/M transition of mitotic cell cycle GO:0000086 9.83 NDE1 PAFAH1B1 TUBA1A YWHAE
5 ciliary basal body-plasma membrane docking GO:0097711 9.81 NDE1 PAFAH1B1 TUBA1A YWHAE
6 sister chromatid cohesion GO:0007062 9.8 NDE1 NUDC PAFAH1B1
7 regulation of G2/M transition of mitotic cell cycle GO:0010389 9.8 NDE1 PAFAH1B1 TUBA1A YWHAE
8 forebrain development GO:0030900 9.73 ARX CDK5 NDE1 RELN
9 dendrite morphogenesis GO:0048813 9.71 CDK5 DCX VLDLR
10 positive regulation of protein kinase activity GO:0045860 9.71 CDK5 DAG1 RELN VLDLR
11 negative regulation of JNK cascade GO:0046329 9.67 FKTN PAFAH1B1
12 axon extension GO:0048675 9.66 CDK5 DCX
13 associative learning GO:0008306 9.66 CDK5 RELN
14 modulation of chemical synaptic transmission GO:0050804 9.65 LRP8 RELN
15 establishment of mitotic spindle orientation GO:0000132 9.65 NDE1 PAFAH1B1
16 positive regulation of dendritic spine morphogenesis GO:0061003 9.65 LRP8 PAFAH1B1 RELN
17 hippocampus development GO:0021766 9.65 CDK5 DCX PAFAH1B1 RELN YWHAE
18 neuroblast proliferation GO:0007405 9.64 NDE1 PAFAH1B1
19 positive regulation of CREB transcription factor activity GO:0032793 9.63 LRP8 RELN
20 protein localization to synapse GO:0035418 9.62 CDK5 RELN
21 positive regulation of dendrite development GO:1900006 9.62 LRP8 VLDLR
22 protein O-linked mannosylation GO:0035269 9.61 FKRP FKTN
23 cellular response to cholesterol GO:0071397 9.61 DAG1 LRP8
24 vesicle transport along microtubule GO:0047496 9.6 NDE1 PAFAH1B1
25 Schwann cell development GO:0014044 9.59 CDK5 DAG1
26 microtubule organizing center organization GO:0031023 9.58 NDE1 PAFAH1B1
27 ventral spinal cord development GO:0021517 9.58 RELN VLDLR
28 regulation of microtubule motor activity GO:2000574 9.56 NDE1 PAFAH1B1
29 cerebral cortex tangential migration GO:0021800 9.55 ARX RELN
30 reelin-mediated signaling pathway GO:0038026 9.5 LRP8 RELN VLDLR
31 layer formation in cerebral cortex GO:0021819 9.46 CDK5 DCX PAFAH1B1 RELN
32 cerebral cortex development GO:0021987 9.43 CDK5 LRP8 NDE1 PAFAH1B1 RELN YWHAE
33 neuron migration GO:0001764 9.17 ARX CDK5 DCX NDE1 PAFAH1B1 RELN
34 multicellular organism development GO:0007275 10.13 ARX DCX NDE1 NUDC PAFAH1B1 RELN
35 cell cycle GO:0007049 10.04 CDK5 KATNB1 NDE1 NUDC PAFAH1B1

Molecular functions related to Lissencephaly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 dynein complex binding GO:0070840 9.37 KATNB1 PAFAH1B1
2 apolipoprotein binding GO:0034185 9.32 LRP8 VLDLR
3 low-density lipoprotein receptor activity GO:0005041 9.26 LRP8 VLDLR
4 very-low-density lipoprotein particle receptor activity GO:0030229 9.16 LRP8 VLDLR
5 microtubule binding GO:0008017 9.02 CDK5 DCX KATNB1 NDE1 PAFAH1B1
6 reelin receptor activity GO:0038025 8.96 LRP8 VLDLR

Sources for Lissencephaly

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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