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 54 50 51 56 71 29 13 52 69
Familial Schizencephaly 50 24 56 69
Schzc 71

Characteristics:

Orphanet epidemiological data:

56
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 : 54
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 familial schizencephaly, shh-related and acquired schizencephaly, and has symptoms including strabismus, seizures and global developmental delay. An important gene associated with Schizencephaly is SIX3 (SIX Homeobox 3), and among its related pathways/superpathways are Ectoderm Differentiation and Development_Hedgehog and PTH signaling pathways in bone and cartilage development. Affiliated tissues include brain, spinal cord and cortex, and related phenotypes are growth/size/body region and mortality/aging

NIH Rare Diseases : 50 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. affected people 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. last updated: 11/17/2014

NINDS : 51 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 : 71 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 : 72 Schizencephaly (from Greek skhizein, meaning \'to split\', and enkephalos, meaning \'brain\') is a rare... more...

Related Diseases for Schizencephaly

Diseases in the Schizencephaly family:

Familial Schizencephaly, Emx2-Related Familial Schizencephaly, Shh-Related
Familial Schizencephaly, Six3-Related Acquired Schizencephaly

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

(show top 50) (show all 114)
id Related Disease Score Top Affiliating Genes
1 familial schizencephaly, shh-related 11.8
2 acquired schizencephaly 11.7
3 familial schizencephaly, emx2-related 11.7
4 familial schizencephaly, six3-related 11.7
5 corpus callosum agenesis 11.3
6 neuronal migration disorders 10.8
7 microcephaly 2, primary, autosomal recessive, with or without cortical malformations 10.8
8 holoprosencephaly 1 10.8
9 silengo lerone pelizza syndrome 10.8
10 hemiplegia 10.7 COL4A1 SIX3
11 nasal cavity inverting papilloma 10.7 COL4A1 SIX3
12 aminoacylase 1 deficiency 10.5 HESX1 SIX3
13 microphthalmia with coloboma 5 10.5 SHH SIX3
14 sporadic pheochromocytoma 10.5 SHH SIX3
15 celosomia 10.5 SHH SIX3
16 hyperostosis 10.5 MTHFR SIX3
17 holoprosencephaly 2 10.4 SHH SIX3
18 pelizaeus-merzbacher disease in female carriers 10.4 SHH SIX3
19 laryngotracheoesophageal cleft type 2 10.4 SHH SIX3
20 laryngotracheoesophageal cleft type 4 10.4 SHH SIX3
21 majeed syndrome 10.4 SHH SIX3
22 isolated facial myokymia 10.4 SHH SIX3
23 cataract 44 10.4 SHH SIX3
24 dyskinetic cerebral palsy 10.3 F5 SIX3
25 pityriasis rotunda 10.3 HESX1 SHH
26 multicentric osteolysis nephropathy 10.2 F5 MTHFR
27 coronary sinus stenosis 10.2 F5 MTHFR
28 amelogenesis imperfecta hypomaturation type 10.2 F5 MTHFR
29 syncope 10.2 F5 MTHFR
30 lockwood feingold syndrome 10.2 F5 MTHFR
31 ring dermoid of cornea 10.2 HESX1 SHH
32 superior limbic keratoconjunctivitis 10.2 F5 MTHFR
33 follicular adenoma 10.2 F5 MTHFR
34 pregnancy loss, recurrent 1 10.2 F5 MTHFR
35 hiv-1 10.2 F5 MTHFR
36 cavernous lymphangioma 10.2 F5 MTHFR
37 rheumatoid lung disease 10.2 F5 MTHFR
38 femoral neuropathy 10.2 F5 MTHFR
39 cryptosporidiosis 10.2 F5 MTHFR
40 intestinal pseudo-obstruction 10.1 F5 MTHFR
41 homologous wasting disease 10.1 F5 MTHFR
42 angiodysplasia 10.1 SHH SIX3 WDR62
43 angular blepharoconjunctivitis 10.1 F5 MTHFR
44 dysgammaglobulinemia 10.1 F5 MTHFR
45 hepatocellular adenoma 10.1 F5 MTHFR
46 renal, genital, and middle ear anomalies 10.1 HESX1 SOX2
47 epilepsy 10.1
48 ulcerative stomatitis 10.1 F5 MTHFR
49 blepharoconjunctivitis 10.0 F5 MTHFR
50 aryepiglottic fold cancer 10.0 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:

56 32 (show all 11)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 strabismus 56 32 hallmark (90%) Very frequent (99-80%) HP:0000486
2 seizures 56 32 frequent (33%) Frequent (79-30%) HP:0001250
3 global developmental delay 56 32 frequent (33%) Frequent (79-30%) HP:0001263
4 intellectual disability 56 32 frequent (33%) Frequent (79-30%) HP:0001249
5 hemiparesis 56 32 frequent (33%) Frequent (79-30%) HP:0001269
6 spastic tetraplegia 56 32 frequent (33%) Frequent (79-30%) HP:0002510
7 porencephaly 56 32 hallmark (90%) Very frequent (99-80%) HP:0002132
8 eeg abnormality 56 32 hallmark (90%) Very frequent (99-80%) HP:0002353
9 aplasia/hypoplasia of the corpus callosum 56 32 hallmark (90%) Very frequent (99-80%) HP:0007370
10 spasticity 56 Very frequent (99-80%)
11 schizencephaly 32 HP:0010636

MGI Mouse Phenotypes related to Schizencephaly:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.1 SHH SIX3 SOX2 WDR62 COL4A1 EMX2
2 mortality/aging MP:0010768 10.02 EMX2 F5 HESX1 LHX2 COL4A1 MTHFR
3 nervous system MP:0003631 10.02 COL4A1 EMX2 F5 HESX1 LHX2 MTHFR
4 embryo MP:0005380 9.98 COL4A1 EMX2 F5 HESX1 SHH SIX3
5 craniofacial MP:0005382 9.93 EMX2 HESX1 LHX2 SHH SIX3 SOX2
6 respiratory system MP:0005388 9.76 LHX2 SHH SIX3 SOX2 WDR62 COL4A1
7 reproductive system MP:0005389 9.73 COL4A1 EMX2 MTHFR SHH SOX2 WDR62
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:


id 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:

id Genetic test Affiliating Genes
1 Schizencephaly 29
2 Familial Schizencephaly 24

Anatomical Context for Schizencephaly

MalaCards organs/tissues related to Schizencephaly:

39
Brain, Spinal Cord, Cortex, Temporal Lobe, Pituitary, Cerebellum, Cingulate Cortex

Publications for Schizencephaly

Articles related to Schizencephaly:

(show top 50) (show all 191)
id Title Authors Year
1
Teaching NeuroImages: Homotopic motor distribution on fMRI in closed-lip schizencephaly. ( 28069984 )
2017
2
Functional brain neuroimaging-guided repetitive transcranial magnetic stimulation in neurodevelopmental disorders: The case of a schizencephaly-related spastic dystonia. ( 28566157 )
2017
3
Successful surgery for refractory seizures associated with bilateral schizencephaly: two case reports and literature review. ( 26966118 )
2016
4
Bilateral giant open-lip schizencephaly: A rare case report. ( 27606022 )
2016
5
Novel COL4A1 mutation in an infant with severe dysmorphic syndrome with schizencephaly, periventricular calcifications, and cataract resembling congenital infection. ( 26879631 )
2016
6
Schizencephaly: A case report and review of literature. ( 27098948 )
2016
7
New-Onset Seizure Associated With Schizencephaly. ( 27727044 )
2016
8
Right Homonymous Hemianopia: A Clinical Case Report of Schizencephaly. ( 26889154 )
2016
9
Contactin-associated protein-like (CNTNAP) 2 gene mutation in a patient with bilateral schizencephaly. ( 27233939 )
2016
10
"Quartered cerebrum": Bilateral schizencephaly with partial agenesis of corpus callosum. ( 27147184 )
2016
11
Neuroepidemiology of Porencephaly, Schizencephaly, and Hydranencephaly in Miyagi Prefecture, Japan. ( 26545857 )
2015
12
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
13
Intracranial sonographic features demonstrating in utero development of hemorrhagic brain damage leading to schizencephaly-associated COL4A1 mutation. ( 26576802 )
2015
14
Schizencephaly-diagnostics and clinical dilemmas. ( 25690450 )
2015
15
Botulinum toxin A injection of UES in schizencephaly with dysphagia: Case report. ( 26351064 )
2015
16
Schizencephaly: Dramatic Images in a Normally Functioning Adult. ( 25828202 )
2015
17
Schizencephaly associated psychosis. ( 26182841 )
2015
18
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
19
Diagnostic imaging and problems of schizencephaly. ( 25473439 )
2014
20
Prenatal Diagnosis and Postnatal Outcome of Schizencephaly. ( 25535059 )
2014
21
Successful Treatment of Refractory Seizures With Rufinamide in Children With Schizencephaly: Report of 3 Cases. ( 25051969 )
2014
22
Correlation of prenatal and postnatal MRI findings in schizencephaly. ( 24610904 )
2014
23
Schizencephaly. . ( 25906523 )
2014
24
Prune belly and schizencephaly. ( 25114199 )
2014
25
Unilateral closed lip schizencephaly with septo-optic dysplasia. ( 24761255 )
2014
26
Bilateral schizencephaly Type II. ( 24719651 )
2014
27
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
28
Medical image. Schizencephaly. ( 25225763 )
2014
29
Large vertex meningoencephalocele with schizencephaly: An interesting case with neurosurgical challenge. ( 25250068 )
2014
30
A case of schizencephaly associated with obsessive-compulsive disorder. ( 23638447 )
2013
31
Long-term outcome of surgical treatment of patients with intractable epilepsy associated with schizencephaly. ( 23793966 )
2013
32
A Case of Schizencephaly Has a Normal Surface EEG but Abnormal Intracranial EEG: Epilepsia Partialis Continua or Dystonia? ( 23545249 )
2013
33
Clinical and Radiologic Features of Unilateral and Bilateral Schizencephaly in Polish Pediatric Patients. ( 23503883 )
2013
34
Schizencephaly: association with young maternal age, alcohol use, and lack of prenatal care. ( 23266945 )
2013
35
Resection or multi-lobe disconnection for intractable epilepsy with open-lip schizencephaly. ( 23896548 )
2013
36
Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly. ( 23225343 )
2013
37
Schizencephaly and borderline personality disorder. ( 23686060 )
2013
38
Schizencephaly and psychosis: a rare association. ( 24454392 )
2013
39
Continuous involuntary hand movements and schizencephaly: epilepsia partialis continua or dystonia? ( 21720895 )
2012
40
The differences in epileptic characteristics in patients with porencephaly and schizencephaly. ( 22024697 )
2012
41
Unilateral open-lip schizencephaly: A rare cause of infantile hemiparesis. ( 23560019 )
2012
42
Schizencephaly of open and closed lip type in the same patient: An extremely rare occurrence. ( 23248687 )
2012
43
Open-lip schizencephaly associated with bipolar disorder in a young man exposed in utero to the chernobyl disaster. ( 22450641 )
2012
44
Prenatal and Postnatal Schizencephaly Findings by 2D and 3D Ultrasound: Pictorial Essay. ( 22754744 )
2012
45
A case of schizencephaly and septo-optic dysplasia presenting with anterior encephalocele. ( 24665280 )
2012
46
Status epilepticus revealing a giant schizencephaly. ( 23159513 )
2012
47
Comorbidity of attention-deficit/hyperactivity disorder, Tourette's syndrome and bipolar I disorder in an adolescent patient with schizencephaly. ( 22285365 )
2012
48
Schizencephaly prevalence, prenatal diagnosis and clues to etiology: a register-based study. ( 21647999 )
2012
49
Schizencephaly: a study of 16 patients. ( 21890242 )
2012
50
Nijmegen breakage syndrome with macrocephaly, schizencephaly and large CSF spacesa89extended spectrum of the condition. ( 22293976 )
2012

Variations for Schizencephaly

UniProtKB/Swiss-Prot genetic disease variations for Schizencephaly:

71
id 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
id 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.499G> T (p.Ala167Ser) single nucleotide variant Pathogenic rs387906868 GRCh37 Chromosome 2, 45169742: 45169742
7 COL4A1 NM_001845.5(COL4A1): c.3976G> A (p.Gly1326Arg) single nucleotide variant Pathogenic rs587777379 GRCh37 Chromosome 13, 110818624: 110818624

Expression for Schizencephaly

Search GEO for disease gene expression data for Schizencephaly.

Pathways for Schizencephaly

Pathways related to Schizencephaly according to GeneCards Suite gene sharing:

id 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:

id 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 20)
id Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.92 EMX2 HESX1 SHH SIX3 SOX2
2 regulation of gene expression GO:0010468 9.71 EMX2 SHH SOX2
3 positive regulation of cell differentiation GO:0045597 9.59 SHH SOX2
4 blood circulation GO:0008015 9.58 F5 MTHFR
5 dorsal/ventral pattern formation GO:0009953 9.58 LHX2 SHH
6 hair follicle development GO:0001942 9.57 LHX2 SHH
7 eye development GO:0001654 9.56 SIX3 SOX2
8 odontogenesis GO:0042476 9.55 BGLAP SHH
9 cerebral cortex development GO:0021987 9.54 EMX2 LHX2 WDR62
10 branching involved in blood vessel morphogenesis GO:0001569 9.51 COL4A1 SHH
11 forebrain development GO:0030900 9.5 EMX2 SHH SOX2
12 telencephalon development GO:0021537 9.49 LHX2 SIX3
13 renal system development GO:0072001 9.48 EMX2 SHH
14 anatomical structure formation involved in morphogenesis GO:0048646 9.46 LHX2 SHH
15 osteoblast development GO:0002076 9.43 BGLAP SHH
16 cell proliferation in forebrain GO:0021846 9.4 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 response to vitamin K GO:0032571 9.26 BGLAP F5
20 telencephalon regionalization GO:0021978 8.8 LHX2 SHH SIX3

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

id 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
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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