SCHZC
MCID: SCH018
MIFTS: 53

Schizencephaly (SCHZC)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Schizencephaly

MalaCards integrated aliases for Schizencephaly:

Name: Schizencephaly 57 75 53 54 59 74 37 29 13 55 6 40 72
Familial Schizencephaly 59 72
Acquired Schizencephaly 59
Schzc 74

Characteristics:

Orphanet epidemiological data:

59
schizencephaly
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: 1-9/100000 (United Kingdom),1-9/100000 (United States); Age of onset: Antenatal,Neonatal; Age of death: any age;

Classifications:



External Ids:

OMIM 57 269160
KEGG 37 H01160
ICD10 via Orphanet 34 Q04.6
UMLS via Orphanet 73 C0266484
MedGen 42 C0266484
UMLS 72 C0266484 C2931870

Summaries for Schizencephaly

OMIM : 57 Brunelli et al. (1996) described schizencephaly as an extremely rare congenital disorder characterized by a full-thickness cleft within the cerebral hemispheres. The clefts are lined with gray matter and most commonly involve the parasylvian regions (Wolpert and Barnes, 1992). Large portions of the cerebral hemispheres may be absent and replaced by cerebrospinal fluid. Two types of schizencephaly have been described, depending on the size of the area involved and the separation of the cleft lips (Wolpert and Barnes, 1992). Type I schizencephaly consists of a fused cleft. This fused pial-ependymal seam forms a furrow in the developing brain, and is lined by polymicrogyric gray matter. In type II schizencephaly, there is a large defect, a holohemispheric cleft in the cerebral cortex filled with fluid and lined by polymicrogyric gray matter. The clinical manifestations depend on the severity of the lesion. Patients with type I are often almost normal; they may have seizures and spasticity. In type II abnormalities, there is usually mental retardation, seizures, hypotonia, spasticity, inability to walk or speak, and blindness. Schizencephaly may be part of the larger phenotypic spectrum of holoprosencephaly (HPE; see 236100). (269160)

MalaCards based summary : Schizencephaly, also known as familial schizencephaly, is related to neuronal migration disorders and holoprosencephaly 1. An important gene associated with Schizencephaly is SIX3 (SIX Homeobox 3), and among its related pathways/superpathways are Hedgehog signaling pathway and Ectoderm Differentiation. Affiliated tissues include brain, cortex and spinal cord, and related phenotypes are eeg abnormality and strabismus

NIH Rare Diseases : 53 Schizencephaly is a rare congenital (present from birth) brain malformation in which abnormal slits or clefts form in the cerebral hemispheres of the brain. The signs and symptoms of this condition may include developmental delay, seizures, and problems with brain-spinal cord communication. People with schizencephaly may also have an abnormally small head (microcephaly); hydrocephalus; intellectual disability; partial or complete paralysis; and/or poor muscle tone (hypotonia). Severity of symptoms depends on many factors including the extent of the clefting and whether or not other brain abnormalities are present. Although the exact cause of schizencephaly is unknown, it has been linked to a variety of genetic and non-genetic factors. Treatment generally consists of physical therapy and drugs to prevent seizures. In cases that are complicated by hydrocephalus, a surgically implanted tube, called a shunt, is often used to divert fluid to another area of the body where it can be absorbed.

NINDS : 54 Schizencephaly is an extremely rare developmental birth defect characterized by abnormal slits, or clefts, in the cerebral hemispheres of the brain.  Babies with clefts in both hemispheres (called bilateral clefts) commonly have developmental delays, delays in speech and language skills, and problems with brain-spinal cord communication.  Individuals with clefts in only one hemisphere (called unilateral clefts) are often paralyzed on one side of the body, but may have average to near-average intelligence.  Individuals with schizencephaly may also have an abnormally small head, cognitive delay and impairment, partial or complete paralysis, or poor muscle tone.  Most will experience seizures.  Some individuals may have an excessive accumulation of fluid in the brain called hydrocephalus.

KEGG : 37
Schizencephaly is a clinically and etiologically heterogeneous cerebral malformation presenting as unilateral or bilateral hemispheric cleft with direct connection between the inner and outer liquor spaces. Gray matter-lined clefts in the cerebral cortex and a range of neurological presentations are characteristic. Mutations in SIX3, SHH, and EMX2 have been reported.

UniProtKB/Swiss-Prot : 74 Schizencephaly: Extremely rare human congenital disorder characterized by a full- thickness cleft within the cerebral hemispheres. These clefts are lined with gray matter and most commonly involve the parasylvian regions. Large portions of the cerebral hemispheres may be absent and replaced by cerebro-spinal fluid.

Wikipedia : 75 Schizencephaly (from Greek skhizein, meaning 'to split', and enkephalos, meaning 'brain') is a rare... more...

Related Diseases for Schizencephaly

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

(show top 50) (show all 173)
# Related Disease Score Top Affiliating Genes
1 neuronal migration disorders 32.8 WDR62 EMX2
2 holoprosencephaly 1 32.5 SIX3 SHH
3 spastic hemiplegia 30.9 SIX3 COL4A1
4 septooptic dysplasia 30.8 SIX3 HESX1
5 hydranencephaly 30.8 SIX3 COL4A1
6 holoprosencephaly 2 30.7 SIX3-AS1 SIX3
7 lobar holoprosencephaly 30.6 SIX3 SHH
8 familial porencephaly 30.6 COL4A2 COL4A1
9 hemiplegia 30.4 COL4A2 COL4A1 BGLAP
10 spastic cerebral palsy 30.3 SIX3 F5
11 encephalomalacia 29.8 SIX3 MTHFR
12 cerebral palsy 29.8 MTHFR F5 COL4A1
13 gastroschisis 29.7 MTHFR F5
14 porencephaly 29.1 SIX3 MTHFR F5 COL4A2 COL4A1
15 corpus callosum, agenesis of 11.7
16 brain small vessel disease 1 with or without ocular anomalies 11.5
17 silengo lerone pelizza syndrome 11.3
18 microcephaly 2, primary, autosomal recessive, with or without cortical malformations 11.2
19 midline interhemispheric variant of holoprosencephaly 10.6 SIX3 SHH
20 septopreoptic holoprosencephaly 10.6 SIX3 SHH
21 alobar holoprosencephaly 10.5 SIX3 SHH
22 microform holoprosencephaly 10.5 SIX3 SHH
23 polymicrogyria with or without vascular-type ehlers-danlos syndrome 10.5
24 polymicrogyria 10.5
25 angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps 10.5 COL4A2 COL4A1
26 semilobar holoprosencephaly 10.5 SIX3 SHH
27 cerebral malformation 10.5
28 chromosome 18p deletion syndrome 10.5 SIX3 SHH
29 seizure disorder 10.4
30 hydrocephalus 10.4
31 congenital hydrocephalus 10.4
32 visual epilepsy 10.3
33 microcephaly 7, primary, autosomal recessive 10.3 WDR62 SHH
34 congenital nervous system abnormality 10.3 WDR62 SIX3 SHH
35 physical disorder 10.3 WDR62 SIX3 SHH
36 epilepsy 10.3
37 microcephaly 10.3
38 corneal dystrophy, posterior polymorphous, 3 10.3 COL4A2 COL4A1
39 encephalocele 10.2
40 optic nerve hypoplasia, bilateral 10.2
41 dystonia 10.2
42 absence of septum pellucidum 10.2
43 pachygyria 10.2
44 quadriplegia 10.2
45 arachnoid cysts 10.2
46 cytomegalovirus infection 10.2
47 hydrocephalus, congenital, 1 10.1
48 corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia 10.1
49 lissencephaly 10.1
50 holoprosencephaly 10.1

Graphical network of the top 20 diseases related to Schizencephaly:



Diseases related to Schizencephaly

Symptoms & Phenotypes for Schizencephaly

Human phenotypes related to Schizencephaly:

59 32 (show all 14)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 eeg abnormality 59 32 hallmark (90%) Very frequent (99-80%) HP:0002353
2 strabismus 59 32 hallmark (90%) Very frequent (99-80%) HP:0000486
3 aplasia/hypoplasia of the corpus callosum 59 32 hallmark (90%) Very frequent (99-80%) HP:0007370
4 porencephalic cyst 32 hallmark (90%) HP:0002132
5 intellectual disability 59 32 frequent (33%) Frequent (79-30%) HP:0001249
6 seizures 59 32 frequent (33%) Frequent (79-30%) HP:0001250
7 global developmental delay 59 32 frequent (33%) Frequent (79-30%) HP:0001263
8 spastic tetraplegia 59 32 frequent (33%) Frequent (79-30%) HP:0002510
9 hemiparesis 59 32 frequent (33%) Frequent (79-30%) HP:0001269
10 agenesis of corpus callosum 32 HP:0001274
11 spasticity 59 Very frequent (99-80%)
12 cerebral cortical atrophy 32 HP:0002120
13 porencephaly 59 Very frequent (99-80%)
14 schizencephaly 32 HP:0010636

Clinical features from OMIM:

269160

MGI Mouse Phenotypes related to Schizencephaly:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.17 COL4A1 COL4A2 EMX2 F5 HESX1 LHX2
2 mortality/aging MP:0010768 10.07 COL4A1 COL4A2 EMX2 F5 HESX1 LHX2
3 embryo MP:0005380 10.06 COL4A1 COL4A2 EMX2 F5 HESX1 SHH
4 nervous system MP:0003631 10.06 COL4A1 COL4A2 EMX2 F5 HESX1 LHX2
5 craniofacial MP:0005382 10.02 COL4A2 EMX2 HESX1 LHX2 SHH SIX3
6 respiratory system MP:0005388 9.81 COL4A1 COL4A2 EMX2 HESX1 LHX2 SHH
7 hearing/vestibular/ear MP:0005377 9.8 COL4A2 EMX2 HESX1 SHH SOX2
8 reproductive system MP:0005389 9.8 COL4A1 COL4A2 EMX2 MTHFR SHH SOX2
9 taste/olfaction MP:0005394 9.43 EMX2 HESX1 LHX2 SHH SIX3 SOX2
10 vision/eye MP:0005391 9.28 COL4A1 COL4A2 EMX2 HESX1 LHX2 MTHFR

Drugs & Therapeutics for Schizencephaly

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Human Epilepsy Genetics--Neuronal Migration Disorders Study Unknown status NCT00041600

Search NIH Clinical Center for Schizencephaly

Genetic Tests for Schizencephaly

Genetic tests related to Schizencephaly:

# Genetic test Affiliating Genes
1 Schizencephaly 29 COL4A1 EMX2 SHH SIX3

Anatomical Context for Schizencephaly

MalaCards organs/tissues related to Schizencephaly:

41
Brain, Cortex, Spinal Cord, Eye, Temporal Lobe, Fetal Brain, Bone

Publications for Schizencephaly

Articles related to Schizencephaly:

(show top 50) (show all 448)
# Title Authors PMID Year
1
A number of schizencephaly patients including 2 brothers are heterozygous for germline mutations in the homeobox gene EMX2. 9 38 8 71
9359037 1997
2
Heterozygous mutations in SIX3 and SHH are associated with schizencephaly and further expand the clinical spectrum of holoprosencephaly. 38 8 71
20157829 2010
3
Germline mutations in the homeobox gene EMX2 in patients with severe schizencephaly. 38 8 71
8528262 1996
4
No major role for the EMX2 gene in schizencephaly. 9 38 8
18409201 2008
5
Comprehensive EMX2 genotyping of a large schizencephaly case series. 9 38 8
17506092 2007
6
Maternally inherited heterozygous sequence change in the sonic hedgehog gene in a male patient with bilateral closed-lip schizencephaly and partial absence of the corpus callosum. 38 8
19533790 2009
7
Schizencephaly: heterogeneous etiologies in a population of 4 million California births. 38 8
16059942 2005
8
Familial schizencephaly. 38 8
8214352 1993
9
Schizencephaly: case report of familial incidence. 38 8
1580960 1992
10
Familial schizencephaly. 38 8
1743422 1991
11
Sonic hedgehog mutations are an uncommon cause of developmental eye anomalies. 71
20425842 2010
12
Clinical spectrum of SIX3-associated mutations in holoprosencephaly: correlation between genotype, phenotype and function. 71
19346217 2009
13
Mutations in the human SIX3 gene in holoprosencephaly are loss of function. 71
18791198 2008
14
Mutational analysis of SHH and GLI3 in anorectal malformations. 71
18655123 2008
15
SONIC HEDGEHOG mutations causing human holoprosencephaly impair neural patterning activity. 71
12709790 2003
16
The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly. 71
10556296 1999
17
Schizencephalies; a study of the congenital clefts in the cerebral mantle; clefts with fused lips. 8
21026933 1946
18
EMX2-independent familial schizencephaly: clinical and genetic analyses. 9 38
15887302 2005
19
Schizencephaly: clinical spectrum, epilepsy, and pathogenesis. 9 38
15921232 2005
20
Developmental anomalies of the scapula-the "omo"st forgotten bone. 9 38
12884444 2003
21
Familial schizencephaly associated with EMX2 mutation. 9 38
9153481 1997
22
Increased Sylvian fissure angle as early sonographic sign of malformation of cortical development. 38
30381845 2019
23
Malignant Hyperthermia and Cerebral Venous Sinus Thrombosis After Ventriculoperitoneal Shunt in Infant with Schizencephaly and COL4A1 Mutation. 38
31029817 2019
24
Persistent falcine sinus with temporo-occipital schizencephaly: case report with a review of literature in relation to the undeveloped vein of Galen and/or straight sinus. 38
31154486 2019
25
Cortical malformations and COL4A1 mutation: Three new cases. 38
30837194 2019
26
Schizencephaly accompanied by occipital encephalocele and deletion of chromosome 22q13.32: a case report. 38
31130048 2019
27
A rare case of super-refractory epileptic status in pregnant woman: Schizencephaly. 38
30012509 2019
28
Latent Schizencephaly With Psychotic Phenotype or Schizophrenia With Schizencephaly? A Case Report and Review of the Literature. 38
29914267 2019
29
Incongruent hemiatrophy and hemiparkinsonism in a patient with schizencephaly. 38
30390483 2018
30
Schizencephaly in children: A single medical center retrospective study. 38
29371079 2018
31
Further refinement of COL4A1 and COL4A2 related cortical malformations. 38
30315939 2018
32
Fetal stroke and cerebrovascular disease: Advances in understanding from lenticulostriate and venous imaging, alloimmune thrombocytopaenia and monochorionic twins. 38
30467085 2018
33
Schizencephaly: A Review of 734 Patients. 38
30501885 2018
34
Schizencephaly revisited. 38
30027296 2018
35
SCREENING OF PROP-1, LHX2 AND POU1F1 MUTATIONS IN PATIENTS WITH ECTOPIC POSTERIOR PITUITARY GLAND. 38
31149275 2018
36
A Patient with Schizencephaly and Agenesis of Corpus Callosum with No Neurological Deficits. 38
30069099 2018
37
Septo-optic Dysplasia : Assessment of Associated Findings with Special Attention to the Olfactory Sulci and Tracts. 38
29663010 2018
38
Novel COL4A1 mutation in a fetus with early prenatal onset of schizencephaly. 38
29760938 2018
39
COL4A1 and fetal vascular origins of schizencephaly. 38
29282339 2018
40
Frontoethmoidal encephalocele presenting in concert with schizencephaly. 38
30603230 2018
41
Neuronal Migration Disorders. 38
29298944 2018
42
Schizencephaly and Porencephaly Due to Fetal Intracranial Hemorrhage: A Report of Two Cases. 38
29434494 2017
43
Stereoelectroencephalography and surgical outcome in polymicrogyria-related epilepsy: A multicentric study. 38
29059488 2017
44
HYDROCEPHALY, SCHIZENCEPHALY, SPONDYLOCOSTAL DYSPLASIA, AND HYPOPARATHYROIDISM IN AN INFANT OF A DIABETIC MOTHER. 38
31149221 2017
45
Prenatal and postnatal evaluation of polymicrogyria with band heterotopia. 38
28828134 2017
46
Application of array comparative genomic hybridization in Korean children under 6 years old with global developmental delay. 38
29042871 2017
47
Clinical and Radiologic Spectrum of Septo-optic Dysplasia: Review of 17 Cases. 38
28482731 2017
48
Functional brain neuroimaging-guided repetitive transcranial magnetic stimulation in neurodevelopmental disorders: The case of a schizencephaly-related spastic dystonia. 38
28566157 2017
49
Imaging of Laser Therapy in Epilepsy. 38
28370739 2017
50
Recurrence of Epileptic Spasms as Reflex Seizures Induced by Eating: A Case Report and Literature Review. 38
28114705 2017

Variations for Schizencephaly

ClinVar genetic disease variations for Schizencephaly:

6 (show all 13)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 EMX2 EMX2, 1-BP INS insertion Pathogenic
2 EMX2 NM_004098.4(EMX2): c.407-1G> A single nucleotide variant Pathogenic 10:119305142-119305142 10:117545631-117545631
3 EMX2 NM_004098.4(EMX2): c.407-4G> T single nucleotide variant Pathogenic 10:119305139-119305139 10:117545628-117545628
4 EMX2 EMX2, G-T, EXON 2, NT1 single nucleotide variant Pathogenic
5 SIX3 NM_005413.4(SIX3): c.385G> T (p.Glu129Ter) single nucleotide variant Pathogenic rs387906867 2:45169628-45169628 2:44942489-44942489
6 SIX3 NM_005413.4(SIX3): c.499G> T (p.Ala167Ser) single nucleotide variant Pathogenic rs387906868 2:45169742-45169742 2:44942603-44942603
7 COL4A1 NM_001845.6(COL4A1): c.1588C> T (p.Pro530Ser) single nucleotide variant Uncertain significance rs145172612 13:110839625-110839625 13:110187278-110187278
8 COL4A1 NM_001845.6(COL4A1): c.7C> A (p.Pro3Thr) single nucleotide variant Uncertain significance rs751749989 13:110959368-110959368 13:110307021-110307021
9 COL4A1 NM_001845.6(COL4A1): c.2093A> G (p.Lys698Arg) single nucleotide variant Uncertain significance rs375318302 13:110835342-110835342 13:110182995-110182995
10 SIX3 NM_005413.4(SIX3): c.127G> T (p.Gly43Cys) single nucleotide variant Uncertain significance rs1436891421 2:45169370-45169370 2:44942231-44942231
11 SHH NM_000193.4(SHH): c.1147G> A (p.Ala383Thr) single nucleotide variant Uncertain significance rs137853341 7:155595836-155595836 7:155803142-155803142
12 SHH NM_000193.4(SHH): c.869G> A (p.Gly290Asp) single nucleotide variant Benign/Likely benign rs104894047 7:155596114-155596114 7:155803420-155803420
13 SIX3 NM_005413.4(SIX3): c.109G> T (p.Gly37Cys) single nucleotide variant Benign/Likely benign rs199823175 2:45169352-45169352 2:44942213-44942213

UniProtKB/Swiss-Prot genetic disease variations for Schizencephaly:

74
# Symbol AA change Variation ID SNP ID
1 COL4A1 p.Gly655Arg VAR_073812
2 COL4A1 p.Gly870Arg VAR_073815
3 COL4A1 p.Gly897Ser VAR_073817
4 COL4A1 p.Gly948Ser VAR_073818 rs155530307
5 COL4A1 p.Gly1041Glu VAR_073819
6 COL4A1 p.Gly1082Glu VAR_073820
7 COL4A1 p.Gly1326Arg VAR_073822 rs587777379
8 COL4A1 p.Gly1332Asp VAR_073823
9 COL4A1 p.Glu1615Lys VAR_073825
10 SIX3 p.Ala167Ser VAR_071343 rs387906868

Expression for Schizencephaly

Search GEO for disease gene expression data for Schizencephaly.

Pathways for Schizencephaly

Pathways related to Schizencephaly according to KEGG:

37
# Name Kegg Source Accession
1 Hedgehog signaling pathway hsa04340

Pathways related to Schizencephaly according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.29 SOX2 SHH HESX1
2 10.82 COL4A2 COL4A1
3 10.63 SOX2 SHH
4 10.42 SOX2 SIX3 HESX1

GO Terms for Schizencephaly

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

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum lumen GO:0005788 9.02 SHH F5 COL4A2 COL4A1 BGLAP
2 collagen type IV trimer GO:0005587 8.96 COL4A2 COL4A1

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

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 eye development GO:0001654 9.57 SOX2 SIX3
2 odontogenesis GO:0042476 9.56 SHH BGLAP
3 regulation of gene expression GO:0010468 9.56 SOX2 SIX3-AS1 SHH EMX2
4 telencephalon development GO:0021537 9.55 SIX3 LHX2
5 branching involved in blood vessel morphogenesis GO:0001569 9.54 SHH COL4A1
6 cerebral cortex development GO:0021987 9.54 WDR62 LHX2 EMX2
7 anatomical structure development GO:0048856 9.51 SIX3 SHH
8 forebrain development GO:0030900 9.5 SOX2 SHH EMX2
9 anatomical structure formation involved in morphogenesis GO:0048646 9.48 SHH LHX2
10 osteoblast development GO:0002076 9.46 SHH BGLAP
11 cell proliferation in forebrain GO:0021846 9.43 SIX3 EMX2
12 collagen-activated tyrosine kinase receptor signaling pathway GO:0038063 9.4 COL4A2 COL4A1
13 brain development GO:0007420 9.35 SIX3 LHX2 HESX1 EMX2 COL4A1
14 pituitary gland development GO:0021983 9.33 SOX2 SIX3 HESX1
15 renal system development GO:0072001 9.19 SHH
16 telencephalon regionalization GO:0021978 8.8 SIX3 SHH LHX2
17 regulation of transcription, DNA-templated GO:0006355 10 SOX2 SIX3 SHH LHX2 HESX1 EMX2

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

# Name GO ID Score Top Affiliating Genes
1 sequence-specific DNA binding GO:0043565 9.02 SOX2 SIX3 LHX2 HESX1 EMX2
2 extracellular matrix structural constituent conferring tensile strength GO:0030020 8.96 COL4A2 COL4A1

Sources for Schizencephaly

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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