MCID: HTR015
MIFTS: 44

Heterotopia, Periventricular malady

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Fetal diseases, Blood diseases, Cardiovascular diseases, Bone diseases, Skin diseases

Aliases & Classifications for Heterotopia, Periventricular

About this section
Sources:
11Disease Ontology, 12diseasecard, 13DISEASES, 24GeneTests, 25Genetics Home Reference, 27GTR, 31ICD10 via Orphanet, 37MedGen, 39MeSH, 40MESH via Orphanet, 48NIH Rare Diseases, 50Novoseek, 52OMIM, 54Orphanet, 62SNOMED-CT, 64The Human Phenotype Ontology, 68UMLS, 69UMLS via Orphanet, 70UniProtKB/Swiss-Prot
See all MalaCards sources

Aliases & Descriptions for Heterotopia, Periventricular:

Name: Heterotopia, Periventricular 52 12
Periventricular Nodular Heterotopia 11 48 24 25 54 27 50 39 13 68
Periventricular Heterotopia 11 48 25 27
Familial Nodular Heterotopia 25 70
Heterotopia, Periventricular, Ehlers-Danlos Variant 68
Periventricular Heterotopia Ehlers-Danlos Variant 70
Periventricular Heterotopia X-Linked Dominant 70
Nodular Heterotopia Bilateral Periventricular 70
Periventricular Nodular Heterotopia 1 70
 
Periventricular Nodular Heterotopia 4 70
Periventricular Heterotopia, X-Linked 68
Paroxysmal Nocturnal Hemoglobinuria 68
Pvnh4 70
Pvnh1 70
Nhbp 70
Bpnh 70
Pnh 24

Characteristics:

Orphanet epidemiological data:

54
periventricular nodular heterotopia:
Inheritance: Autosomal recessive,X-linked dominant

HPO:

64
heterotopia, periventricular:
Inheritance: x-linked dominant inheritance

Classifications:



External Ids:

OMIM52 300049
Disease Ontology11 DOID:0050454
MeSH39 D054091
Orphanet54 ORPHA98892
SNOMED-CT62 448227009
MESH via Orphanet40 D054091
UMLS via Orphanet69 C1868720
ICD10 via Orphanet31 Q04.8

Summaries for Heterotopia, Periventricular

About this section
OMIM:52 Periventricular nodular heterotopia is a disorder of neuronal migration in which neurons fail to migrate appropriately... (300049) more...

MalaCards based summary: Heterotopia, Periventricular, also known as periventricular nodular heterotopia, is related to periventricular nodular heterotopia 6 and heterotopia, periventricular, ed variant, and has symptoms including seizures, intellectual disability, mild and stroke. An important gene associated with Heterotopia, Periventricular is FLNA (Filamin A), and among its related pathways are Lissencephaly gene (LIS1) in neuronal migration and development and Cytoskeletal Signaling. Affiliated tissues include brain, fetal brain and cortex, and related mouse phenotypes are growth/size/body region and behavior/neurological.

Disease Ontology:11 A congenital nervous system abnormality characterized by non proper migration of neurons during the early development of the fetal brain.

Genetics Home Reference:25 Periventricular heterotopia is a condition in which nerve cells (neurons) do not migrate properly during the early development of the fetal brain, from about the 6th week to the 24th week of pregnancy. Heterotopia means "out of place." In normal brain development, neurons form in the periventricular region, located around fluid-filled cavities (ventricles) near the center of the brain. The neurons then migrate outward to form the exterior of the brain (cerebral cortex) in six onion-like layers. In periventricular heterotopia, some neurons fail to migrate to their proper position and form clumps around the ventricles.

NIH Rare Diseases:48 Periventricular heterotopia is a condition in which the nerve cells (neurons) do not migrate properly during the early development of the fetal brain from about the 6th week to the 24th week of pregnancy. Affected people typically develop recurrent seizures (epilepsy) beginning in mid-adolescence. Intelligence is generally normal; however, some affected people may have mild intellectual disability, including difficulty with reading and/or spelling. Less common signs and symptoms include microcephaly, developmental delay, recurrent infections, and blood vessel abnormalities. Some cases are caused by changes (mutations) in the FLNA gene and are inherited in an X-linked dominant manner. Others are caused by mutations in the ARFGEF2 gene and are inherited in an autosomal recessive manner. Rarely, periventricular heterotopia is associated with duplication of genetic material on chromosome 5. Treatment is generally focused on managing recurrent seizures with medications. Last updated: 10/6/2015

UniProtKB/Swiss-Prot:70 Periventricular nodular heterotopia 1: A developmental disorder characterized by the presence of periventricular nodules of cerebral gray matter, resulting from a failure of neurons to migrate normally from the lateral ventricular proliferative zone, where they are formed, to the cerebral cortex. PVNH1 is an X-linked dominant form. Heterozygous females have normal intelligence but suffer from seizures and various manifestations outside the central nervous system, especially related to the vascular system. Hemizygous affected males die in the prenatal or perinatal period.

Related Diseases for Heterotopia, Periventricular

About this section

Diseases in the Heterotopia, Periventricular family:

Heterotopia, Periventricular, Ed Variant

Diseases related to Heterotopia, Periventricular via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 39)
idRelated DiseaseScoreTop Affiliating Genes
1periventricular nodular heterotopia 612.5
2heterotopia, periventricular, ed variant12.2
3paroxysmal nocturnal hemoglobinuria11.8
4periventricular nodular heterotopia 311.2
5flna-related periventricular nodular heterotopia11.2
6paroxysmal nocturnal hemoglobinuria, somatic11.1
7periventricular heterotopia with microcephaly11.0
8periventricular nodular heterotopia 511.0
9hemoglobinuria10.6
10dfnx1 nonsyndromic hearing loss and deafness10.5DCX, PAFAH1B1
11epilepsy, familial temporal lobe, 710.5PAFAH1B1, RELN
12premature ovarian failure 810.4PAFAH1B1, RELN
13myopathy with deficiency of iron-sulfur cluster assembly enzyme10.4DCX, PAFAH1B1, RELN
14mixed receptive-expressive language disorder10.3ARFGEF2, SIX3, SRPX2
15retinitis pigmentosa 1310.3DCX, PAFAH1B1, RELN
16noonan syndrome 1010.3DCX, PAFAH1B1
17hepatitis d10.3SIX3, SRPX2
18mental retardation, x-linked, syndromic 1510.2DCX, PAFAH1B1
19pseudopelade of brocq10.1DCX, PAFAH1B1, RELN, TUBA1A
20hyperphosphatemia10.1DCX, PAFAH1B1, RELN, TUBA1A
21aplastic anemia10.0
22neonatal infective mastitis10.0AKT3, DCX, FLNA
23autosomal dominant nonsyndromic deafness10.0AKT3, DCX, EMX2
24leukemia10.0
25boomerang dysplasia10.0FLNA, FLNB
26gitelman syndrome9.9ADGRG1, SRPX2
27amyotrophic lateral sclerosis 189.9PAFAH1B1, TUBA1A, TUBA3D
28lymphoblastic leukemia9.8
29end stage renal failure9.7
30pancytopenia9.7
31hyperinsulinism9.7
32tropical spastic paraparesis9.7
33tuberculosis9.7
34miliary tuberculosis9.7
35spastic paraparesis9.7
36spasticity9.7
37endotheliitis9.7
38o'sullivan-mcleod syndrome9.1ADGRG1, ARFGEF2, DCX, EMX2, FLNA, PAFAH1B1
39gastric antral vascular ectasia9.0ARFGEF2, DCX, FLNA, PAFAH1B1, RELN, SIX3

Graphical network of the top 20 diseases related to Heterotopia, Periventricular:



Diseases related to heterotopia, periventricular

Symptoms & Phenotypes for Heterotopia, Periventricular

About this section

Symptoms by clinical synopsis from OMIM:

300049

Clinical features from OMIM:

300049

Human phenotypes related to Heterotopia, Periventricular:

 64 (show all 8)
id Description HPO Frequency HPO Source Accession
1 seizures64 HP:0001250
2 intellectual disability, mild64 HP:0001256
3 stroke64 HP:0001297
4 patent ductus arteriosus64 HP:0001643
5 bicuspid aortic valve64 HP:0001647
6 abnormality of neuronal migration64 HP:0002269
7 heterotopia64 HP:0002282
8 abnormality of the coagulation cascade64 HP:0003256

UMLS symptoms related to Heterotopia, Periventricular:


chyluria, pneumatouria, traumatic hematuria, mahler sign

MGI Mouse Phenotypes related to Heterotopia, Periventricular according to GeneCards Suite gene sharing:

41
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053788.0AKT3, ARFGEF2, DCX, EMX2, FLNA, FLNB
2MP:00053867.9ADGRG1, AKT3, DCX, EMX2, FLNA, FLNB
3MP:00053847.7ADGRG1, AKT3, ARFGEF2, CUX2, EMX2, FLNA
4MP:00107687.3AKT3, ARFGEF2, CUX2, DCX, EMX2, FLNA
5MP:00036315.7ADGRG1, AKT3, ARFGEF2, CUX2, DCX, EMX2

Drugs & Therapeutics for Heterotopia, Periventricular

About this section

Interventional clinical trials:

idNameStatusNCT IDPhase
1Epilepsy Phenome/Genome ProjectUnknown statusNCT00552045

Search NIH Clinical Center for Heterotopia, Periventricular


Cochrane evidence based reviews: periventricular nodular heterotopia

Genetic Tests for Heterotopia, Periventricular

About this section

Genetic tests related to Heterotopia, Periventricular:

id Genetic test Affiliating Genes
1 Periventricular Nodular Heterotopia27 24
2 Periventricular Heterotopia27

Anatomical Context for Heterotopia, Periventricular

About this section

MalaCards organs/tissues related to Heterotopia, Periventricular:

36
Brain, Fetal brain, Cortex

Publications for Heterotopia, Periventricular

About this section

Variations for Heterotopia, Periventricular

About this section

UniProtKB/Swiss-Prot genetic disease variations for Heterotopia, Periventricular:

70
id Symbol AA change Variation ID SNP ID
1FLNAp.Leu656PheVAR_012834rs137853311
2FLNAp.Glu82ValVAR_015699rs28935169
3FLNAp.Ala39GlyVAR_022734rs137853313
4FLNAp.Met102ValVAR_031305
5FLNAp.Ala128ValVAR_031306rs137853315
6FLNAp.Ser149PheVAR_031307
7FLNAp.Val528MetVAR_031309rs143873938

Clinvar genetic disease variations for Heterotopia, Periventricular:

5 (show all 51)
id Gene Variation Type Significance SNP ID Assembly Location
1FLNANM_001110556.1(FLNA): c.544C> T (p.Gln182Ter)SNVPathogenicrs137853310GRCh37Chr X, 153596288: 153596288
2FLNANM_001110556.1(FLNA): c.720+2T> CSNVPathogenicrs863223295GRCh37Chr X, 153596007: 153596007
3FLNANM_001110556.1(FLNA): c.623-3C> GSNVPathogenicrs398123622GRCh37Chr X, 153596109: 153596109
4FLNANM_001110556.1(FLNA): c.373+1G> ASNVPathogenicrs863223296GRCh38Chr X, 154370872: 154370872
5FLNANM_001110556.1(FLNA): c.287_291delGGCCC (p.Arg96Hisfs)deletionPathogenicrs863223297GRCh37Chr X, 153599323: 153599327
6FLNANM_001110556.1(FLNA): c.1966C> T (p.Leu656Phe)SNVPathogenicrs137853311GRCh37Chr X, 153592950: 153592950
7FLNANM_001110556.1(FLNA): c.6915C> G (p.Tyr2305Ter)SNVPathogenicrs781910090GRCh37Chr X, 153580057: 153580057
8FLNANM_001110556.1(FLNA): c.245A> T (p.Glu82Val)SNVPathogenicrs28935169GRCh37Chr X, 153599369: 153599369
9FLNANM_001110556.1(FLNA): c.760G> A (p.Glu254Lys)SNVPathogenicrs28935470GRCh37Chr X, 153595873: 153595873
10FLNAFLNA, 1-BP DEL, 2762GdeletionPathogenicChr na, -1: -1
11FLNANM_001110556.1(FLNA): c.4147delG (p.Ala1383Leufs)deletionPathogenicrs863223299GRCh38Chr X, 154359402: 154359402
12FLNANM_001110556.1(FLNA): c.116C> G (p.Ala39Gly)SNVPathogenicrs137853313GRCh37Chr X, 153599498: 153599498
13FLNANM_001110556.1(FLNA): c.383C> T (p.Ala128Val)SNVPathogenicrs137853315GRCh37Chr X, 153596449: 153596449
14FLNANM_001110556.1(FLNA): c.1923C> T (p.Gly641=)SNVPathogenicrs80338841GRCh37Chr X, 153592993: 153592993
15FLNANM_001110556.1(FLNA): c.7757-1G> CSNVPathogenicrs797044496GRCh37Chr X, 153577405: 153577405
16FLNANM_001110556.1(FLNA): c.7153C> T (p.Gln2385Ter)SNVPathogenicrs727503931GRCh38Chr X, 154350912: 154350912
17FLNANM_001456.3(FLNA): c.4777_4778dupAA (p.Thr1594Argfs)duplicationPathogenicrs786200973GRCh37Chr X, 153585969: 153585970
18FLNANM_001110556.1(FLNA): c.1430-1G> TSNVPathogenicrs786205177GRCh38Chr X, 154365487: 154365487
19FLNANM_001110556.1(FLNA): c.6635_6638delTCAG (p.Val2212Alafs)deletionPathogenicrs786205178GRCh37Chr X, 153580680: 153580683
20FLNANM_001110556.1(FLNA): c.1045G> T (p.Glu349Ter)SNVLikely pathogenicrs370490152GRCh37Chr X, 153594950: 153594950
21FLNANM_001110556.1(FLNA): c.1061_1065delATAAG (p.His354Argfs)deletionLikely pathogenicrs786205180GRCh37Chr X, 153594930: 153594934
22FLNANM_001110556.1(FLNA): c.137delA (p.Gln46Argfs)deletionLikely pathogenicrs786205181GRCh38Chr X, 154371109: 154371109
23FLNANM_001110556.1(FLNA): c.1722T> A (p.Cys574Ter)SNVLikely pathogenicrs786205182GRCh38Chr X, 154364927: 154364927
24FLNANM_001110556.1(FLNA): c.1829-2A> GSNVPathogenicrs786205183GRCh38Chr X, 154364721: 154364721
25FLNANM_001110556.1(FLNA): c.2565+1G> CSNVPathogenicrs786205186GRCh38Chr X, 154362417: 154362417
26FLNANM_001110556.1(FLNA): c.3529delG (p.Glu1177Argfs)deletionLikely pathogenicrs786205188GRCh38Chr X, 154360266: 154360266
27FLNANM_001110556.1(FLNA): c.3875_3888dupACGTCAAGGCCCGT (p.Val1297Thrfs)duplicationLikely pathogenicrs786205189GRCh37Chr X, 153588191: 153588204
28FLNANM_001110556.1(FLNA): c.3980-5_3990dup16duplicationLikely pathogenicrs786205190GRCh38Chr X, 154359636: 154359651
29FLNANM_001110556.1(FLNA): c.4006delG (p.Asp1336Thrfs)deletionLikely pathogenicrs786205191GRCh37Chr X, 153587988: 153587988
30FLNANM_001110556.1(FLNA): c.4617_4618delGC (p.Leu1540Alafs)deletionLikely pathogenicrs786205194GRCh38Chr X, 154358336: 154358337
31FLNANM_001110556.1(FLNA): c.4935C> A (p.Cys1645Ter)SNVLikely pathogenicrs786205197GRCh37Chr X, 153585812: 153585812
32FLNANM_001110556.1(FLNA): c.4943delC (p.Thr1648Lysfs)deletionLikely pathogenicrs786205198GRCh38Chr X, 154357436: 154357436
33FLNANM_001110556.1(FLNA): c.5021_5022delTG (p.Val1674Glyfs)deletionLikely pathogenicrs786205199GRCh37Chr X, 153583388: 153583389
34FLNANM_001110556.1(FLNA): c.6355_6356delAA (p.Lys2119Valfs)deletionPathogenicrs786205201GRCh38Chr X, 154352795: 154352796
35FLNANM_001110556.1(FLNA): c.6580G> T (p.Glu2194Ter)SNVLikely pathogenicrs786205202GRCh38Chr X, 154352370: 154352370
36FLNANM_001110556.1(FLNA): c.732dupC (p.Glu245Argfs)duplicationLikely pathogenicrs786205203GRCh38Chr X, 154367533: 154367533
37FLNANM_001110556.1(FLNA): c.987+1G> ASNVLikely pathogenicrs786205204GRCh38Chr X, 154366731: 154366731
38FLNANM_001110556.1(FLNA): c.4269_4277delCCTCAACGTinsTGGC (p.Leu1424Glyfs)indelPathogenicrs797044690GRCh37Chr X, 153587640: 153587648
39FLNANM_001110556.1(FLNA): c.5854delG (p.Val1952Serfs)deletionPathogenicrs797044724GRCh37Chr X, 153581928: 153581928
40FLNANM_001110556.1(FLNA): c.5278C> T (p.Gln1760Ter)SNVPathogenicrs886044824GRCh37Chr X, 153583019: 153583019
41FLNANM_001110556.1(FLNA): c.2339_2340insAA (p.Lys781Thrfs)insertionPathogenicGRCh37Chr X, 153591093: 153591094
42FLNANM_001110556.1(FLNA): c.2319_2320insAA (p.Val774Lysfs)insertionPathogenicGRCh37Chr X, 153591113: 153591114
43FLNANM_001110556.1(FLNA): c.2405-2A> GSNVPathogenicrs886044850GRCh37Chr X, 153590948: 153590948
44FLNANM_001110556.1(FLNA): c.7896G> A (p.Trp2632Ter)SNVPathogenicrs398122812GRCh37Chr X, 153577265: 153577265
45FLNANM_001110556.1(FLNA): c.4450C> T (p.Gln1484Ter)SNVPathogenicGRCh38Chr X, 154359008: 154359008
46FLNANM_001110556.1(FLNA): c.2761C> T (p.Arg921Ter)SNVPathogenicrs398123614GRCh37Chr X, 153590412: 153590412
47FLNANM_001110556.1(FLNA): c.3153dupC (p.Val1052Argfs)duplicationPathogenicrs398123616GRCh37Chr X, 153589730: 153589730
48FLNANM_001110556.1(FLNA): c.42delC (p.Ala15Argfs)deletionPathogenicrs398123619GRCh37Chr X, 153599572: 153599572
49FLNANM_001110556.1(FLNA): c.4447_4448insAT (p.Leu1483Tyrfs)insertionPathogenicrs398123620GRCh37Chr X, 153587378: 153587379
50FLNANM_001110556.1(FLNA): c.4543C> T (p.Arg1515Ter)SNVPathogenicrs186214592GRCh37Chr X, 153586868: 153586868
51FLNANM_001110556.1(FLNA): c.5132_5133delTCinsAA (p.Phe1711Ter)indelPathogenicrs398123621GRCh37Chr X, 153583277: 153583278

Copy number variations for Heterotopia, Periventricular from CNVD:

6 (show all 22)
id CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1137431127800000Deletionperiventricular nodular heterotopia
2158162213050000046944323MicrodeletionAP001042.1periventricular nodular heterotopia
3158165213050000046944323MicrodeletionBRWD1periventricular nodular heterotopia
4158168213050000046944323MicrodeletionC21orf24periventricular nodular heterotopia
5158171213050000046944323MicrodeletionDSCR10periventricular nodular heterotopia
6158174213050000046944323MicrodeletionDSCR3periventricular nodular heterotopia
7158177213050000046944323MicrodeletionDSCR4periventricular nodular heterotopia
8158180213050000046944323MicrodeletionDSCR6periventricular nodular heterotopia
9158183213050000046944323MicrodeletionDSCR8periventricular nodular heterotopia
10158186213050000046944323MicrodeletionDSCR9periventricular nodular heterotopia
11158189213050000046944323MicrodeletionDYRK1Aperiventricular nodular heterotopia
12158192213050000046944323MicrodeletionERGperiventricular nodular heterotopia
13158195213050000046944323MicrodeletionETS2periventricular nodular heterotopia
14158198213050000046944323MicrodeletionHLCSperiventricular nodular heterotopia
15158201213050000046944323MicrodeletionKCNJ15periventricular nodular heterotopia
16158204213050000046944323MicrodeletionKCNJ6periventricular nodular heterotopia
17158207213050000046944323MicrodeletionPIGPperiventricular nodular heterotopia
18158210213050000046944323MicrodeletionPSMG1periventricular nodular heterotopia
19158214213050000046944323MicrodeletionTTC3periventricular nodular heterotopia
20160229221180000024300000Deletionperiventricular nodular heterotopia
2122769077180000077400000Deletionperiventricular nodular heterotopia
22260192X146900000154913754Copy numberperiventricular nodular heterotopia

Expression for genes affiliated with Heterotopia, Periventricular

About this section
Search GEO for disease gene expression data for Heterotopia, Periventricular.

Pathways for genes affiliated with Heterotopia, Periventricular

About this section

GO Terms for genes affiliated with Heterotopia, Periventricular

About this section

Biological processes related to Heterotopia, Periventricular according to GeneCards Suite gene sharing:

(show all 11)
idNameGO IDScoreTop Affiliating Genes
1cell proliferation in forebrainGO:002184610.6EMX2, SIX3
2hippocampus developmentGO:002176610.4DCX, PAFAH1B1, RELN
3cerebral cortex developmentGO:002198710.3EMX2, PAFAH1B1, RELN
4neuron migrationGO:000176410.2DCX, PAFAH1B1, RELN
5positive regulation of excitatory postsynaptic potentialGO:200046310.1CUX2, RELN
6positive regulation of dendritic spine morphogenesisGO:006100310.0CUX2, PAFAH1B1, RELN
7regulation of ARF protein signal transductionGO:003201210.0ARFGEF2, GBF1
8cerebral cortex regionalizationGO:002179610.0ADGRG1, EMX2
9microtubule-based processGO:00070179.9PAFAH1B1, TUBA1A, TUBA3D
10layer formation in cerebral cortexGO:00218199.5ADGRG1, DCX, PAFAH1B1, RELN
11brain developmentGO:00074209.0ADGRG1, DCX, EMX2, PAFAH1B1, RELN, SIX3

Molecular functions related to Heterotopia, Periventricular according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1ARF guanyl-nucleotide exchange factor activityGO:000508610.0ARFGEF2, GBF1

Sources for Heterotopia, Periventricular

About this section
2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
27GTR
28HGMD
29HMDB
30ICD10
31ICD10 via Orphanet
32ICD9CM
33IUPHAR
34KEGG
37MedGen
39MeSH
40MESH via Orphanet
41MGI
44NCI
45NCIt
46NDF-RT
49NINDS
50Novoseek
52OMIM
53OMIM via Orphanet
57PubMed
58QIAGEN
63SNOMED-CT via Orphanet
67Tumor Gene Family of Databases
68UMLS
69UMLS via Orphanet