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 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

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. 

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.

Wikipedia : 76 Schizencephaly (from Greek, Modern skhizein, meaning ''to split'', and enkephalos, meaning ''brain'')... 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 108)
# Related Disease Score Top Affiliating Genes
1 acquired schizencephaly 33.2 EMX2 SHH SIX3
2 holoprosencephaly 1 31.9 SHH SIX3
3 neuronal migration disorders 31.8 EMX2 WDR62
4 septooptic dysplasia 30.5 HESX1 SIX3
5 hydranencephaly 30.3 COL4A1 SIX3
6 porencephaly 30.1 COL4A1 F5 MTHFR SIX3
7 brain small vessel disease with or without ocular anomalies 30.1 COL4A1 SIX3
8 lobar holoprosencephaly 30.0 SHH SIX3
9 spastic cerebral palsy 29.9 F5 SIX3
10 cerebral palsy 29.7 COL4A1 F5 MTHFR
11 corpus callosum, agenesis of 11.5
12 silengo lerone pelizza syndrome 11.1
13 microcephaly 2, primary, autosomal recessive, with or without cortical malformations 11.1
14 epilepsy 10.3
15 spastic hemiplegia 10.3 COL4A1 SIX3
16 holoprosencephaly 2 10.2 SIX3 SIX3-AS1
17 septopreoptic holoprosencephaly 10.2 SHH SIX3
18 midline interhemispheric variant of holoprosencephaly 10.2 SHH SIX3
19 polymicrogyria 10.2
20 alobar holoprosencephaly 10.2 SHH SIX3
21 microform holoprosencephaly 10.2 SHH SIX3
22 chromosome 18p deletion syndrome 10.2 SHH SIX3
23 semilobar holoprosencephaly 10.2 SHH SIX3
24 microcephaly 7, primary, autosomal recessive 10.1 SHH WDR62
25 encephalomalacia 10.1 MTHFR SIX3
26 dystonia 10.1
27 congenital nervous system abnormality 10.1 SHH SIX3 WDR62
28 physical disorder 10.1 SHH SIX3 WDR62
29 inferior vena cava interruption 10.1 F5 MTHFR
30 amaurosis fugax 10.1 F5 MTHFR
31 spinal cord infarction 10.1 F5 MTHFR
32 sudden sensorineural hearing loss 10.1 F5 MTHFR
33 cryptogenic cirrhosis 10.1 F5 MTHFR
34 catastrophic antiphospholipid syndrome 10.1 F5 MTHFR
35 retinal vascular occlusion 10.1 F5 MTHFR
36 thrombophlebitis 10.1 F5 MTHFR
37 gastroschisis 10.1 F5 MTHFR
38 antithrombin iii deficiency 10.0 F5 MTHFR
39 schizophrenia 10.0
40 holoprosencephaly 10.0
41 central retinal vein occlusion 10.0 F5 MTHFR
42 retinal vein occlusion 10.0 F5 MTHFR
43 intracranial thrombosis 10.0 F5 MTHFR
44 blood protein disease 10.0 F5 MTHFR
45 retinal artery occlusion 10.0 F5 MTHFR
46 portal vein thrombosis 10.0 F5 MTHFR
47 pulmonary artery disease 10.0 F5 MTHFR
48 arteritic anterior ischemic optic neuropathy 10.0 F5 MTHFR
49 cleidocranial dysplasia 10.0 BGLAP SHH
50 pituitary stalk interruption syndrome 10.0 HESX1 SHH

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 14)
# 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 agenesis of corpus callosum 32 HP:0001274
10 spasticity 59 Very frequent (99-80%)
11 cerebral cortical atrophy 32 HP:0002120
12 porencephaly 59 Very frequent (99-80%)
13 schizencephaly 32 HP:0010636
14 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 10.1 COL4A1 EMX2 F5 HESX1 LHX2 MTHFR
2 embryo MP:0005380 9.98 COL4A1 EMX2 F5 HESX1 SHH SIX3
3 mortality/aging MP:0010768 9.97 COL4A1 EMX2 F5 HESX1 LHX2 MTHFR
4 nervous system MP:0003631 9.96 COL4A1 EMX2 F5 HESX1 LHX2 MTHFR
5 craniofacial MP:0005382 9.93 EMX2 HESX1 LHX2 SHH SIX3 SOX2
6 liver/biliary system MP:0005370 9.77 F5 LHX2 MTHFR SHH WDR62
7 respiratory system MP:0005388 9.76 COL4A1 EMX2 HESX1 LHX2 SHH SIX3
8 taste/olfaction MP:0005394 9.43 EMX2 HESX1 LHX2 SHH SIX3 SOX2
9 vision/eye MP:0005391 9.23 COL4A1 EMX2 HESX1 LHX2 MTHFR SHH

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, Eye, Bone, Pituitary, Placenta

Publications for Schizencephaly

Articles related to Schizencephaly:

(show top 50) (show all 205)
# 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
A rare case of super-refractory epileptic status in pregnant woman: Schizencephaly. ( 30012509 )
2018
6
Schizencephaly revisited. ( 30027296 )
2018
7
A Patient with Schizencephaly and Agenesis of Corpus Callosum with No Neurological Deficits. ( 30069099 )
2018
8
Incongruent hemiatrophy and hemiparkinsonism in a patient with schizencephaly. ( 30390483 )
2018
9
Schizencephaly: A Review of 734 Patients. ( 30501885 )
2018
10
Teaching NeuroImages: Homotopic motor distribution on fMRI in closed-lip schizencephaly. ( 28069984 )
2017
11
A rare case of schizencephaly in an adult with late presentation. ( 29302567 )
2017
12
Functional brain neuroimaging-guided repetitive transcranial magnetic stimulation in neurodevelopmental disorders: The case of a schizencephaly-related spastic dystonia. ( 28566157 )
2017
13
Schizencephaly and Porencephaly Due to Fetal Intracranial Hemorrhage: A Report of Two Cases. ( 29434494 )
2017
14
New-Onset Seizure Associated With Schizencephaly. ( 27727044 )
2017
15
&amp;quot;Quartered cerebrum&amp;quot;: Bilateral schizencephaly with partial agenesis of corpus callosum. ( 27147184 )
2016
16
Bilateral giant open-lip schizencephaly: A rare case report. ( 27606022 )
2016
17
Successful surgery for refractory seizures associated with bilateral schizencephaly: two case reports and literature review. ( 26966118 )
2016
18
Novel COL4A1 mutation in an infant with severe dysmorphic syndrome with schizencephaly, periventricular calcifications, and cataract resembling congenital infection. ( 26879631 )
2016
19
Right Homonymous Hemianopia: A Clinical Case Report of Schizencephaly. ( 26889154 )
2016
20
Schizencephaly: A case report and review of literature. ( 27098948 )
2016
21
Contactin-associated protein-like (CNTNAP) 2 gene mutation in a patient with bilateral schizencephaly. ( 27233939 )
2016
22
Schizencephaly associated psychosis. ( 26182841 )
2015
23
Neuroepidemiology of Porencephaly, Schizencephaly, and Hydranencephaly in Miyagi Prefecture, Japan. ( 26545857 )
2015
24
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
25
Schizencephaly: Dramatic Images in a Normally Functioning Adult. ( 25828202 )
2015
26
Schizencephaly-diagnostics and clinical dilemmas. ( 25690450 )
2015
27
Intracranial sonographic features demonstrating in utero development of hemorrhagic brain damage leading to schizencephaly-associated COL4A1 mutation. ( 26576802 )
2015
28
Botulinum toxin A injection of UES in schizencephaly with dysphagia: Case report. ( 26351064 )
2015
29
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
30
Unilateral closed lip schizencephaly with septo-optic dysplasia. ( 24761255 )
2014
31
Successful Treatment of Refractory Seizures With Rufinamide in Children With Schizencephaly: Report of 3 Cases. ( 25051969 )
2014
32
Correlation of prenatal and postnatal MRI findings in schizencephaly. ( 24610904 )
2014
33
Prenatal Diagnosis and Postnatal Outcome of Schizencephaly. ( 25535059 )
2014
34
Medical image. Schizencephaly. ( 25225763 )
2014
35
Diagnostic imaging and problems of schizencephaly. ( 25473439 )
2014
36
Bilateral schizencephaly Type II. ( 24719651 )
2014
37
Schizencephaly. . ( 25906523 )
2014
38
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
39
Prune belly and schizencephaly. ( 25114199 )
2014
40
Large vertex meningoencephalocele with schizencephaly: An interesting case with neurosurgical challenge. ( 25250068 )
2014
41
Long-term outcome of surgical treatment of patients with intractable epilepsy associated with schizencephaly. ( 23793966 )
2013
42
A Case of Schizencephaly Has a Normal Surface EEG but Abnormal Intracranial EEG: Epilepsia Partialis Continua or Dystonia? ( 23545249 )
2013
43
Schizencephaly: association with young maternal age, alcohol use, and lack of prenatal care. ( 23266945 )
2013
44
Resection or multi-lobe disconnection for intractable epilepsy with open-lip schizencephaly. ( 23896548 )
2013
45
Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly. ( 23225343 )
2013
46
A case of schizencephaly associated with obsessive-compulsive disorder. ( 23638447 )
2013
47
Schizencephaly and psychosis: a rare association. ( 24454392 )
2013
48
Schizencephaly and borderline personality disorder. ( 23686060 )
2013
49
Clinical and Radiologic Features of Unilateral and Bilateral Schizencephaly in Polish Pediatric Patients. ( 23503883 )
2013
50
Schizencephaly prevalence, prenatal diagnosis and clues to etiology: a register-based study. ( 21647999 )
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 rs587777379
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 18)
# Gene Variation Type Significance SNP ID Assembly Location
1 SHH NM_000193.3(SHH): c.1147G> A (p.Ala383Thr) single nucleotide variant Uncertain significance rs137853341 GRCh37 Chromosome 7, 155595836: 155595836
2 SHH NM_000193.3(SHH): c.1147G> A (p.Ala383Thr) single nucleotide variant Uncertain significance rs137853341 GRCh38 Chromosome 7, 155803142: 155803142
3 SHH NM_000193.3(SHH): c.869G> A (p.Gly290Asp) single nucleotide variant Conflicting interpretations of pathogenicity rs104894047 GRCh37 Chromosome 7, 155596114: 155596114
4 SHH NM_000193.3(SHH): c.869G> A (p.Gly290Asp) single nucleotide variant Conflicting interpretations of pathogenicity rs104894047 GRCh38 Chromosome 7, 155803420: 155803420
5 EMX2 EMX2, 1-BP INS insertion Pathogenic
6 EMX2 EMX2, IVS1AS, G-A, -1 single nucleotide variant Pathogenic
7 EMX2 EMX2, IVS1AS, G-T, -4 single nucleotide variant Pathogenic
8 EMX2 EMX2, G-T, EXON 2, NT1 single nucleotide variant Pathogenic
9 SIX3 NM_005413.3(SIX3): c.385G> T (p.Glu129Ter) single nucleotide variant Pathogenic rs387906867 GRCh37 Chromosome 2, 45169628: 45169628
10 SIX3 NM_005413.3(SIX3): c.385G> T (p.Glu129Ter) single nucleotide variant Pathogenic rs387906867 GRCh38 Chromosome 2, 44942489: 44942489
11 SIX3 NM_005413.3(SIX3): c.109G> T (p.Gly37Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs199823175 GRCh37 Chromosome 2, 45169352: 45169352
12 SIX3 NM_005413.3(SIX3): c.109G> T (p.Gly37Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs199823175 GRCh38 Chromosome 2, 44942213: 44942213
13 SIX3 NM_005413.3(SIX3): c.499G> T (p.Ala167Ser) single nucleotide variant Pathogenic rs387906868 GRCh37 Chromosome 2, 45169742: 45169742
14 SIX3 NM_005413.3(SIX3): c.499G> T (p.Ala167Ser) single nucleotide variant Pathogenic rs387906868 GRCh38 Chromosome 2, 44942603: 44942603
15 COL4A1 NM_001845.5(COL4A1): c.3976G> A (p.Gly1326Arg) single nucleotide variant Pathogenic rs587777379 GRCh37 Chromosome 13, 110818624: 110818624
16 COL4A1 NM_001845.5(COL4A1): c.3976G> A (p.Gly1326Arg) single nucleotide variant Pathogenic rs587777379 GRCh38 Chromosome 13, 110166277: 110166277
17 COL4A1 NM_001845.5(COL4A1): c.3104G> T (p.Gly1035Val) single nucleotide variant Pathogenic GRCh37 Chromosome 13, 110827659: 110827659
18 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 11.29 HESX1 SHH SOX2
2 10.85 BGLAP SHH
3 10.63 SHH SOX2
4 10.42 HESX1 SIX3 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 21)
# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.95 EMX2 HESX1 SHH SIX3 SOX2
2 regulation of transcription, DNA-templated GO:0006355 9.91 EMX2 HESX1 LHX2 SHH SIX3 SOX2
3 positive regulation of cell differentiation GO:0045597 9.6 SHH SOX2
4 dorsal/ventral pattern formation GO:0009953 9.59 LHX2 SHH
5 hair follicle development GO:0001942 9.58 LHX2 SHH
6 blood circulation GO:0008015 9.58 F5 MTHFR
7 eye development GO:0001654 9.57 SIX3 SOX2
8 odontogenesis GO:0042476 9.56 BGLAP SHH
9 regulation of gene expression GO:0010468 9.56 EMX2 SHH SIX3-AS1 SOX2
10 telencephalon development GO:0021537 9.54 LHX2 SIX3
11 cerebral cortex development GO:0021987 9.54 EMX2 LHX2 WDR62
12 branching involved in blood vessel morphogenesis GO:0001569 9.52 COL4A1 SHH
13 anatomical structure development GO:0048856 9.51 SHH SIX3
14 forebrain development GO:0030900 9.5 EMX2 SHH SOX2
15 anatomical structure formation involved in morphogenesis GO:0048646 9.49 LHX2 SHH
16 renal system development GO:0072001 9.48 EMX2 SHH
17 osteoblast development GO:0002076 9.46 BGLAP SHH
18 cell proliferation in forebrain GO:0021846 9.4 EMX2 SIX3
19 brain development GO:0007420 9.35 COL4A1 EMX2 HESX1 LHX2 SIX3
20 pituitary gland development GO:0021983 9.33 HESX1 SIX3 SOX2
21 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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