MCID: SCH018
MIFTS: 52

Schizencephaly

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

Aliases & Classifications for Schizencephaly

MalaCards integrated aliases for Schizencephaly:

Name: Schizencephaly 57 76 53 54 59 75 37 29 13 55 6 40 73
Familial Schizencephaly 53 59 73
Schzc 75

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:



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 acquired schizencephaly and holoprosencephaly 1. An important gene associated with Schizencephaly is COL4A1 (Collagen Type IV Alpha 1 Chain), and among its related pathways/superpathways are Hedgehog signaling pathway and Ectoderm Differentiation. Affiliated tissues include brain, spinal cord and cortex, and related phenotypes are intellectual disability and seizures

UniProtKB/Swiss-Prot : 75 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.

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. 

Wikipedia : 76 Schizencephaly (from Greek skhizein, meaning \'to split\', and enkephalos, meaning \'brain\') is a rare... more...

Related Diseases for Schizencephaly

Diseases in the Schizencephaly family:

Acquired Schizencephaly

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

(show top 50) (show all 113)
# Related Disease Score Top Affiliating Genes
1 acquired schizencephaly 33.3 EMX2 SHH SIX3
2 holoprosencephaly 1 32.2 SHH SIX3
3 septooptic dysplasia 30.7 HESX1 SIX3
4 lobar holoprosencephaly 30.4 SHH SIX3
5 spastic cerebral palsy 30.0 F5 SIX3
6 porencephaly 29.4 COL4A1 F5 MTHFR SIX3
7 cerebral palsy 29.3 COL4A1 F5 MTHFR
8 corpus callosum, agenesis of 11.4
9 silengo lerone pelizza syndrome 10.9
10 microcephaly 2, primary, autosomal recessive, with or without cortical malformations 10.9
11 neuronal migration disorders 10.9
12 spastic hemiplegia 10.8 COL4A1 SIX3
13 holoprosencephaly 2 10.7 SIX3 SIX3-AS1
14 septopreoptic holoprosencephaly 10.6 SHH SIX3
15 midline interhemispheric variant of holoprosencephaly 10.6 SHH SIX3
16 alobar holoprosencephaly 10.6 SHH SIX3
17 chromosome 18p deletion syndrome 10.6 SHH SIX3
18 microform holoprosencephaly 10.6 SHH SIX3
19 semilobar holoprosencephaly 10.5 SHH SIX3
20 encephalomalacia 10.5 MTHFR SIX3
21 congenital nervous system abnormality 10.3 SHH SIX3 WDR62
22 physical disorder 10.3 SHH SIX3 WDR62
23 fryns microphthalmia syndrome 10.2 HESX1 SOX2
24 pituitary stalk interruption syndrome 10.2 HESX1 SHH
25 inferior vena cava interruption 10.2 F5 MTHFR
26 axenfeld-rieger syndrome, type 1 10.2 HESX1 SHH
27 amaurosis fugax 10.2 F5 MTHFR
28 spinal cord infarction 10.2 F5 MTHFR
29 livedoid vasculopathy 10.2 F5 MTHFR
30 esophageal atresia 10.2 SHH SOX2
31 sudden sensorineural hearing loss 10.2 F5 MTHFR
32 catastrophic antiphospholipid syndrome 10.2 F5 MTHFR
33 cryptogenic cirrhosis 10.2 F5 MTHFR
34 retinal artery occlusion 10.1 F5 MTHFR
35 epilepsy 10.1
36 intracranial thrombosis 10.1 F5 MTHFR
37 retinal vascular occlusion 10.1 F5 MTHFR
38 thrombophlebitis 10.1 F5 MTHFR
39 antithrombin iii deficiency 10.1 F5 MTHFR
40 central retinal vein occlusion 10.1 F5 MTHFR
41 portal vein thrombosis 10.1 F5 MTHFR
42 patent foramen ovale 10.1 F5 MTHFR
43 arteritic anterior ischemic optic neuropathy 10.0 F5 MTHFR
44 polymicrogyria 10.0
45 protein s deficiency 10.0 F5 MTHFR
46 vein disease 10.0 F5 MTHFR
47 cerebritis 10.0
48 placental abruption 10.0 F5 MTHFR
49 thrombasthenia 10.0 F5 MTHFR
50 protein c deficiency 9.9 F5 MTHFR

Graphical network of the top 20 diseases related to Schizencephaly:



Diseases related to Schizencephaly

Symptoms & Phenotypes for Schizencephaly

Clinical features from OMIM:

269160

Human phenotypes related to Schizencephaly:

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

MGI Mouse Phenotypes related to Schizencephaly:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.07 COL4A1 EMX2 F5 HESX1 LHX2 MTHFR
2 mortality/aging MP:0010768 9.97 COL4A1 F5 HESX1 LHX2 MTHFR SHH
3 nervous system MP:0003631 9.96 COL4A1 EMX2 F5 HESX1 LHX2 MTHFR
4 embryo MP:0005380 9.95 COL4A1 EMX2 F5 HESX1 SHH SIX3
5 craniofacial MP:0005382 9.91 EMX2 HESX1 LHX2 SHH SIX3 SOX2
6 respiratory system MP:0005388 9.76 COL4A1 EMX2 HESX1 LHX2 SHH SIX3
7 taste/olfaction MP:0005394 9.43 HESX1 LHX2 SHH SIX3 SOX2 EMX2
8 vision/eye MP:0005391 9.23 SHH SIX3 SOX2 COL4A1 EMX2 HESX1

Drugs & Therapeutics for Schizencephaly

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Human Epilepsy Genetics--Neuronal Migration Disorders Study Recruiting 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, Spinal Cord, Cortex, Temporal Lobe, Pituitary, Cerebellum, Cingulate Cortex

Publications for Schizencephaly

Articles related to Schizencephaly:

(show top 50) (show all 199)
# Title Authors Year
1
Novel <i>COL4A1</i> mutation in a fetus with early prenatal onset of schizencephaly. ( 29760938 )
2018
2
Schizencephaly in children: A single medical center retrospective study. ( 29371079 )
2018
3
<i>COL4A1</i> and fetal vascular origins of schizencephaly. ( 29282339 )
2018
4
Latent Schizencephaly With Psychotic Phenotype or Schizophrenia With Schizencephaly? A Case Report and Review of the Literature. ( 29914267 )
2018
5
Teaching NeuroImages: Homotopic motor distribution on fMRI in closed-lip schizencephaly. ( 28069984 )
2017
6
A rare case of schizencephaly in an adult with late presentation. ( 29302567 )
2017
7
Functional brain neuroimaging-guided repetitive transcranial magnetic stimulation in neurodevelopmental disorders: The case of a schizencephaly-related spastic dystonia. ( 28566157 )
2017
8
Schizencephaly and Porencephaly Due to Fetal Intracranial Hemorrhage: A Report of Two Cases. ( 29434494 )
2017
9
&amp;quot;Quartered cerebrum&amp;quot;: Bilateral schizencephaly with partial agenesis of corpus callosum. ( 27147184 )
2016
10
Bilateral giant open-lip schizencephaly: A rare case report. ( 27606022 )
2016
11
Successful surgery for refractory seizures associated with bilateral schizencephaly: two case reports and literature review. ( 26966118 )
2016
12
Novel COL4A1 mutation in an infant with severe dysmorphic syndrome with schizencephaly, periventricular calcifications, and cataract resembling congenital infection. ( 26879631 )
2016
13
Right Homonymous Hemianopia: A Clinical Case Report of Schizencephaly. ( 26889154 )
2016
14
Schizencephaly: A case report and review of literature. ( 27098948 )
2016
15
Contactin-associated protein-like (CNTNAP) 2 gene mutation in a patient with bilateral schizencephaly. ( 27233939 )
2016
16
New-Onset Seizure Associated With Schizencephaly. ( 27727044 )
2016
17
Schizencephaly associated psychosis. ( 26182841 )
2015
18
Neuroepidemiology of Porencephaly, Schizencephaly, and Hydranencephaly in Miyagi Prefecture, Japan. ( 26545857 )
2015
19
ERRATA: Intracranial Hemorrhage and Tortuosity of Veins Detected on Susceptibility-weighted Imaging of a Child with a Type IV Collagen I+1 Mutation and Schizencephaly. ( 26567609 )
2015
20
Schizencephaly: Dramatic Images in a Normally Functioning Adult. ( 25828202 )
2015
21
Schizencephaly-diagnostics and clinical dilemmas. ( 25690450 )
2015
22
Intracranial sonographic features demonstrating in utero development of hemorrhagic brain damage leading to schizencephaly-associated COL4A1 mutation. ( 26576802 )
2015
23
Botulinum toxin A injection of UES in schizencephaly with dysphagia: Case report. ( 26351064 )
2015
24
Prenatal diagnosis of chromosome 8p23.1 microdeletion by array comparative genomic hybridization using uncultured amniocytes in a pregnancy associated with fetal partial corpus callosum agenesis and schizencephaly. ( 26701010 )
2015
25
Unilateral closed lip schizencephaly with septo-optic dysplasia. ( 24761255 )
2014
26
Successful Treatment of Refractory Seizures With Rufinamide in Children With Schizencephaly: Report of 3 Cases. ( 25051969 )
2014
27
Correlation of prenatal and postnatal MRI findings in schizencephaly. ( 24610904 )
2014
28
Prenatal Diagnosis and Postnatal Outcome of Schizencephaly. ( 25535059 )
2014
29
Medical image. Schizencephaly. ( 25225763 )
2014
30
Diagnostic imaging and problems of schizencephaly. ( 25473439 )
2014
31
Bilateral schizencephaly Type II. ( 24719651 )
2014
32
Schizencephaly. . ( 25906523 )
2014
33
Intracranial Hemorrhage and Tortuosity of Veins Detected on Susceptibility-weighted Imaging of a Child with a Type IV Collagen I+1 Mutation and Schizencephaly. ( 25500781 )
2014
34
Prune belly and schizencephaly. ( 25114199 )
2014
35
Large vertex meningoencephalocele with schizencephaly: An interesting case with neurosurgical challenge. ( 25250068 )
2014
36
Long-term outcome of surgical treatment of patients with intractable epilepsy associated with schizencephaly. ( 23793966 )
2013
37
A Case of Schizencephaly Has a Normal Surface EEG but Abnormal Intracranial EEG: Epilepsia Partialis Continua or Dystonia? ( 23545249 )
2013
38
Schizencephaly: association with young maternal age, alcohol use, and lack of prenatal care. ( 23266945 )
2013
39
Resection or multi-lobe disconnection for intractable epilepsy with open-lip schizencephaly. ( 23896548 )
2013
40
Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly. ( 23225343 )
2013
41
A case of schizencephaly associated with obsessive-compulsive disorder. ( 23638447 )
2013
42
Schizencephaly and psychosis: a rare association. ( 24454392 )
2013
43
Schizencephaly and borderline personality disorder. ( 23686060 )
2013
44
Clinical and Radiologic Features of Unilateral and Bilateral Schizencephaly in Polish Pediatric Patients. ( 23503883 )
2013
45
Schizencephaly prevalence, prenatal diagnosis and clues to etiology: a register-based study. ( 21647999 )
2012
46
Continuous involuntary hand movements and schizencephaly: epilepsia partialis continua or dystonia? ( 21720895 )
2012
47
Unilateral open-lip schizencephaly: A rare cause of infantile hemiparesis. ( 23560019 )
2012
48
The differences in epileptic characteristics in patients with porencephaly and schizencephaly. ( 22024697 )
2012
49
A case of schizencephaly and septo-optic dysplasia presenting with anterior encephalocele. ( 24665280 )
2012
50
Status epilepticus revealing a giant schizencephaly. ( 23159513 )
2012

Variations for Schizencephaly

UniProtKB/Swiss-Prot genetic disease variations for Schizencephaly:

75
# 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
5 COL4A1 p.Gly1041Glu VAR_073819
6 COL4A1 p.Gly1082Glu VAR_073820
7 COL4A1 p.Gly1326Arg VAR_073822
8 COL4A1 p.Gly1332Asp VAR_073823
9 COL4A1 p.Glu1615Lys VAR_073825
10 SIX3 p.Ala167Ser VAR_071343 rs387906868

ClinVar genetic disease variations for Schizencephaly:

6
(show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 EMX2 EMX2, 1-BP INS insertion Pathogenic
2 EMX2 EMX2, IVS1AS, G-A, -1 single nucleotide variant Pathogenic
3 EMX2 EMX2, IVS1AS, G-T, -4 single nucleotide variant Pathogenic
4 EMX2 EMX2, G-T, EXON 2, NT1 single nucleotide variant Pathogenic
5 SIX3 NM_005413.3(SIX3): c.385G> T (p.Glu129Ter) single nucleotide variant Pathogenic rs387906867 GRCh37 Chromosome 2, 45169628: 45169628
6 SIX3 NM_005413.3(SIX3): c.385G> T (p.Glu129Ter) single nucleotide variant Pathogenic rs387906867 GRCh38 Chromosome 2, 44942489: 44942489
7 SIX3 NM_005413.3(SIX3): c.499G> T (p.Ala167Ser) single nucleotide variant Pathogenic rs387906868 GRCh37 Chromosome 2, 45169742: 45169742
8 SIX3 NM_005413.3(SIX3): c.499G> T (p.Ala167Ser) single nucleotide variant Pathogenic rs387906868 GRCh38 Chromosome 2, 44942603: 44942603
9 COL4A1 NM_001845.5(COL4A1): c.3976G> A (p.Gly1326Arg) single nucleotide variant Pathogenic rs587777379 GRCh37 Chromosome 13, 110818624: 110818624
10 COL4A1 NM_001845.5(COL4A1): c.3976G> A (p.Gly1326Arg) single nucleotide variant Pathogenic rs587777379 GRCh38 Chromosome 13, 110166277: 110166277
11 COL4A1 NM_001845.5(COL4A1): c.3104G> T (p.Gly1035Val) single nucleotide variant Pathogenic GRCh37 Chromosome 13, 110827659: 110827659
12 COL4A1 NM_001845.5(COL4A1): c.3104G> T (p.Gly1035Val) single nucleotide variant Pathogenic GRCh38 Chromosome 13, 110175312: 110175312

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 10.96 HESX1 SHH SOX2
2 10.75 BGLAP SHH
3 10.43 SHH SOX2

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 8.92 BGLAP COL4A1 F5 SHH

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

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.95 EMX2 HESX1 SHH SIX3 SOX2
2 regulation of gene expression GO:0010468 9.73 EMX2 SHH SOX2
3 positive regulation of cell differentiation GO:0045597 9.58 SHH SOX2
4 blood circulation GO:0008015 9.58 F5 MTHFR
5 dorsal/ventral pattern formation GO:0009953 9.57 LHX2 SHH
6 hair follicle development GO:0001942 9.54 LHX2 SHH
7 eye development GO:0001654 9.52 SIX3 SOX2
8 odontogenesis GO:0042476 9.51 BGLAP SHH
9 forebrain development GO:0030900 9.5 EMX2 SHH SOX2
10 branching involved in blood vessel morphogenesis GO:0001569 9.49 COL4A1 SHH
11 telencephalon development GO:0021537 9.48 LHX2 SIX3
12 anatomical structure formation involved in morphogenesis GO:0048646 9.46 LHX2 SHH
13 renal system development GO:0072001 9.43 EMX2 SHH
14 cerebral cortex development GO:0021987 9.43 EMX2 LHX2 WDR62
15 osteoblast development GO:0002076 9.4 BGLAP SHH
16 cell proliferation in forebrain GO:0021846 9.37 EMX2 SIX3
17 brain development GO:0007420 9.35 COL4A1 EMX2 HESX1 LHX2 SIX3
18 pituitary gland development GO:0021983 9.33 HESX1 SIX3 SOX2
19 telencephalon regionalization GO:0021978 8.8 LHX2 SHH SIX3

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 EMX2 HESX1 LHX2 SIX3 SOX2

Sources for Schizencephaly

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 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 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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