CCM1
MCID: CRB103
MIFTS: 50

Cerebral Cavernous Malformations-1 (CCM1) malady

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

Aliases & Classifications for Cerebral Cavernous Malformations-1

Aliases & Descriptions for Cerebral Cavernous Malformations-1:

Name: Cerebral Cavernous Malformations-1 54
Cerebral Cavernous Malformation 12 50 25 51 29 14
Cerebral Cavernous Malformations 1 66 29 69
Ccm 12 50 25
Cavernous Malformations of Cns and Retina 54 13
Familial Cerebral Cavernous Malformation 25 69
Cavernous Angiomatous Malformations 12 66
Cerebral Capillary Malformations 12 66
Cerebral Cavernous Hemangioma 50 25
Familial Cavernous Angioma 12 66
Cavernous Angioma 50 51
Hyperkeratotic Cutaneous Capillary-Venous Malformations Associated with Cerebral Capillary Malformations 54
Hemangioma, Cavernous, Central Nervous System 42
Central Nervous System Cavernous Hemangioma 25
Familial Cerebral Cavernous Angioma 25
Intracerebral Cavernous Hemangioma 25
Cavernous Hemangioma of the Brain 66
Cerebral Cavernous Malformations 52
Familial Cavernous Malformation 25
Familial Cavernous Hemangioma 25
Hemangioma, Cavernous 69
Cerebral Cavernoma 66
Angioma, Cavernous 69
Cavernoma 50
Ccm1 66

Characteristics:

HPO:

32
cerebral cavernous malformations-1:
Inheritance autosomal dominant inheritance heterogeneous
Onset and clinical course incomplete penetrance


Classifications:



External Ids:

OMIM 54 116860
Disease Ontology 12 DOID:0060669
MeSH 42 D020786

Summaries for Cerebral Cavernous Malformations-1

NIH Rare Diseases : 50 cerebral cavernous malformations (ccms) are collections of small blood vessels (capillaries) in the brain that are enlarged and irregular in structure which lead to altered blood flow. cavernous malformations can occur anywhere in the body, but usually produce serious signs and symptoms only when they occur in the central nervous system (the brain and spinal cord). cavernous malformations in the brain and/or spinal cord are called cerebral cavernous malformations.  approximately 25 percent of individuals with cerebral cavernous malformations never experience any related medical problems. other people with cerebral cavernous malformations may experience serious symptoms such as headaches, seizures, paralysis, hearing or vision deficiencies, and bleeding in the brain (cerebral hemorrhage). these malformations can change in size and number over time, but they do not become cancerous. this condition can be sporadic or it can be inherited in an autosomal dominant pattern. mutations in the krit1(ccm1), ccm2, and pdcd10 (ccm3) genes cause cerebral cavernous malformation. treatment depends upon the symptoms. seizures are usually treated with antiepileptic medications or surgery. last updated: 12/14/2015

MalaCards based summary : Cerebral Cavernous Malformations-1, also known as cerebral cavernous malformation, is related to cerebral cavernous malformations 3 and cerebral cavernous malformation, familial, and has symptoms including headache, seizures and cerebral calcification. An important gene associated with Cerebral Cavernous Malformations-1 is KRIT1 (KRIT1, Ankyrin Repeat Containing), and among its related pathways/superpathways are Focal Adhesion and Development Endothelin-1/EDNRA signaling. The drugs Anticholesteremic Agents and Antimetabolites have been mentioned in the context of this disorder. Affiliated tissues include brain, spinal cord and endothelial, and related phenotypes are cardiovascular system and mortality/aging

Disease Ontology : 12 A vascular anomaly of the central nervous system characterized by dilated blood-filled capillaries lacking structural support.

Genetics Home Reference : 25 Cerebral cavernous malformations are collections of small blood vessels (capillaries) in the brain that are enlarged and irregular in structure. These capillaries have abnormally thin walls, and they lack other support tissues, such as elastic fibers, which normally make them stretchy. As a result, the blood vessels are prone to leakage, which can cause the health problems related to this condition. Cavernous malformations can occur anywhere in the body, but usually produce serious signs and symptoms only when they occur in the brain and spinal cord (which are described as cerebral).

OMIM : 54 Cerebral cavernous angiomas are relatively rare vascular malformations that may involve any part of the central nervous... (116860) more...

NINDS : 51 Cerebral cavernous malformations (CCMs) are vascular lesions comprised of clusters of tightly packed, abnormally thin-walled small blood vessels (capillaries) that displace normal neurological tissue in the brain or spinal cord. The vessels are filled with slow-moving or stagnant blood that is usually clotted or in a state of decomposition. Cavernous malformations can occur in the brain, spinal cord, and some other body regions. In the brain and spinal cord these cavernous lesions are quite fragile and are prone to bleeding, causing hemorrhagic strokes (bleeding into the brain), seizures, and neurological deficits. CCMs can range in size from a few fractions of an inch to several inches in diameter, depending on the number of blood vessels involved. Some people develop multiple lesions while others never experience related medical problems. Hereditary forms of CCM are caused by mutations in one of three CCM disease genes: CCM1, CCM2, and CCM3. A large population with hereditary CCM disease is found in New Mexico and the Southwestern United States, in which the disease is caused by mutations in the gene CCM1 (or KRIT1).

UniProtKB/Swiss-Prot : 66 Cerebral cavernous malformations 1: A congenital vascular anomaly of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several centimeters.

Related Diseases for Cerebral Cavernous Malformations-1

Diseases in the Cerebral Cavernous Malformations-2 family:

Cerebral Cavernous Malformations 3 Cerebral Cavernous Malformations-1
Cerebral Cavernous Malformation, Familial Familial Cerebral Cavernous Malformation 1
Familial Cerebral Cavernous Malformation 2 Familial Cerebral Cavernous Malformation 3
Familial Cerebral Cavernous Malformation 4

Diseases related to Cerebral Cavernous Malformations-1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 44)
id Related Disease Score Top Affiliating Genes
1 cerebral cavernous malformations 3 12.5
2 cerebral cavernous malformation, familial 12.3
3 intracranial cavernous angioma 12.1
4 familial cerebral cavernous malformation 2 12.1
5 familial cerebral cavernous malformation 3 12.1
6 familial cerebral cavernous malformation 4 12.0
7 familial cerebral cavernous malformation 1 12.0
8 dermal unilateral segmental cavernous angioma 11.9
9 cerebral cavernous malformations-2 11.9
10 cerebrocostomandibular syndrome 11.6
11 cavernous malformation 11.5
12 cavernous hemangioma 11.5
13 congenital vascular cavernous malformations 11.0
14 familial hemangioma 11.0
15 vascular erectile tumor 11.0
16 venous malformations, multiple cutaneous and mucosal 11.0
17 alcoholic psychosis 10.2 KRIT1 SNRPB
18 paget's disease of bone 10.2 KRIT1 SNRPB
19 cerebritis 10.2
20 adult pineoblastoma 10.2 KRIT1 SNRPB
21 pierre robin syndrome and oligodactyly 10.2 CDKN3 PTEN
22 hemiplegic migraine 10.2 KDR PECAM1
23 chondrodysplasia punctata 1, x-linked 10.2 CCM2 KRIT1 PDCD10
24 keratosis follicularis spinulosa decalvans 10.2 KDR PECAM1
25 ichthyosis lamellar 1 10.2 CCM2 KRIT1 PDCD10
26 nail disorder, nonsyndromic congenital, 10, 10.2 CCM2 KRIT1 PDCD10
27 macrocephaly/autism syndrome 10.2 CDKN3 PTEN
28 weyers ulnar ray/oligodactyly syndrome 10.1 CCM2 KRIT1 PDCD10
29 pustulosis palmaris et plantaris 10.1 KDR PECAM1
30 subependymal glioma 10.1 KDR KRIT1
31 vesiculobullous skin disease 10.1 KDR PECAM1
32 hemolytic anemia 10.1 KDR KRIT1 PECAM1
33 neuropathy with hearing impairment 10.1 KDR PECAM1
34 benign idiopathic neonatal seizures 10.0 KDR PECAM1
35 acromesomelic dysplasia, maroteaux type 10.0 CCM2 KRIT1 PDCD10 PTEN
36 cerebellar astrocytoma 10.0 CCM2 KRIT1 PDCD10 SNRPB
37 orofaciodigital syndrome iv 10.0 PDCD10 PTEN SNRPB
38 melanoma, cutaneous malignant, 6 10.0 CDKN3 PTEN
39 hemangioma 9.9
40 chronic pain 9.5 CCM2 ITGB1BP1 KRIT1 MAP3K3 PDCD10 PTEN
41 pallister-hall syndrome 9.4 CCM2 KRIT1 MAP3K3 PDCD10 RAP1A SNRPB
42 retinitis pigmentosa 68 9.3 CCM2 ITGB1BP1 KRIT1 MAP3K3 PDCD10 SNRPB
43 pineal parenchymal tumor of intermediate differentiation 9.0 CCM2 ITGB1BP1 KRIT1 MAP3K3 PDCD10 RAP1A
44 charcot-marie-tooth disease, axonal, type 2f 8.5 CCM2 CDKN3 ITGB1BP1 KDR KRIT1 MAP3K3

Graphical network of the top 20 diseases related to Cerebral Cavernous Malformations-1:



Diseases related to Cerebral Cavernous Malformations-1

Symptoms & Phenotypes for Cerebral Cavernous Malformations-1

Symptoms by clinical synopsis from OMIM:

116860

Clinical features from OMIM:

116860

Human phenotypes related to Cerebral Cavernous Malformations-1:

32 (show all 8)
id Description HPO Frequency HPO Source Accession
1 headache 32 HP:0002315
2 seizures 32 HP:0001250
3 cerebral calcification 32 HP:0002514
4 abnormality of the musculature 32 HP:0003011
5 intracranial hemorrhage 32 HP:0002170
6 abnormality of the skin 32 HP:0000951
7 retinal vascular malformation 32 HP:0007797
8 hepatic vascular malformations 32 HP:0006576

MGI Mouse Phenotypes related to Cerebral Cavernous Malformations-1:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.97 RAP1A STRN CCM2 KDR KRIT1 MAP3K3
2 mortality/aging MP:0010768 9.81 CCM2 ITGB1BP1 KDR KRIT1 MAP3K3 PDCD10
3 embryo MP:0005380 9.73 PDCD10 PTEN CCM2 KDR KRIT1 MAP3K3
4 muscle MP:0005369 9.5 CCM2 KDR KRIT1 MAP3K3 PDCD10 PECAM1
5 vision/eye MP:0005391 9.1 CCM2 ITGB1BP1 KDR KRIT1 PDCD10 PTEN

Drugs & Therapeutics for Cerebral Cavernous Malformations-1

Drugs for Cerebral Cavernous Malformations-1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 17)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1 Anticholesteremic Agents Phase 1, Phase 2,Early Phase 1
2 Antimetabolites Phase 1, Phase 2,Early Phase 1
3 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 1, Phase 2,Early Phase 1
4 Hypolipidemic Agents Phase 1, Phase 2,Early Phase 1
5 Lipid Regulating Agents Phase 1, Phase 2,Early Phase 1
6 Atorvastatin Calcium Phase 1, Phase 2 134523-03-8
7 Calcium, Dietary Phase 1, Phase 2
8
Doxycycline Approved, Investigational, Vet_approved Phase 1 564-25-0 54671203
9 Anti-Bacterial Agents Phase 1
10 Anti-Infective Agents Phase 1
11 Antimalarials Phase 1
12 Antiparasitic Agents Phase 1
13 Antiprotozoal Agents Phase 1
14
Simvastatin Approved Early Phase 1 79902-63-9 54454
15
Diazepam Approved, Illicit, Vet_approved 439-14-5 3016
16 Neuroserpin
17 Astragalus Nutraceutical

Interventional clinical trials:


id Name Status NCT ID Phase
1 Atorvastatin Therapy in Cerebral Cavernous Malformation, Exploratory Proof of Concept Trial Not yet recruiting NCT02603328 Phase 1, Phase 2
2 Influence of MMP on Brain AVM Hemorrhage Completed NCT00783523 Phase 1
3 Genetic Disease Gene Identification Unknown status NCT00916903
4 Permeability MRI in Cerebral Cavernous Malformations Type 1 in New Mexico: Effects of Statins Completed NCT01764451 Early Phase 1
5 CoHOrt of Cerebral CavernOus maLformATion: multicEnter Prospective Observational Study Recruiting NCT02946866
6 Modifiers of Disease Severity in Cerebral Cavernous Malformations Recruiting NCT01764529
7 Implementing Health Plan-Level Care Management for Solo & Small Practices Active, not recruiting NCT02041962

Search NIH Clinical Center for Cerebral Cavernous Malformations-1

Cochrane evidence based reviews: hemangioma, cavernous, central nervous system

Genetic Tests for Cerebral Cavernous Malformations-1

Genetic tests related to Cerebral Cavernous Malformations-1:

id Genetic test Affiliating Genes
1 Cerebral Cavernous Malformation 29
2 Cerebral Cavernous Malformations 1 29

Anatomical Context for Cerebral Cavernous Malformations-1

MalaCards organs/tissues related to Cerebral Cavernous Malformations-1:

39
Brain, Spinal Cord, Endothelial, Retina, Skin

Publications for Cerebral Cavernous Malformations-1

Variations for Cerebral Cavernous Malformations-1

UniProtKB/Swiss-Prot genetic disease variations for Cerebral Cavernous Malformations-1:

66
id Symbol AA change Variation ID SNP ID
1 KRIT1 p.Phe97Ser VAR_023573
2 KRIT1 p.Lys569Glu VAR_023574

ClinVar genetic disease variations for Cerebral Cavernous Malformations-1:

6 (show all 13)
id Gene Variation Type Significance SNP ID Assembly Location
1 KRIT1 KRIT1, 1283C-T single nucleotide variant Pathogenic
2 KRIT1 KRIT1, 1-BP DEL, 1342A deletion Pathogenic
3 KRIT1 KRIT1, 1-BP INS, 1271C insertion Pathogenic
4 KRIT1 NM_194456.1(KRIT1): c.1363C> T (p.Gln455Ter) single nucleotide variant Pathogenic rs267607203 GRCh37 Chromosome 7, 91852184: 91852184
5 KRIT1 KRIT1, 1-BP DEL, 103G deletion Pathogenic
6 KRIT1 KRIT1, IVS2DS, T-C, +2 single nucleotide variant Pathogenic
7 KRIT1 KRIT1, 2-BP DEL, 741TC deletion Pathogenic
8 KRIT1 NM_194456.1(KRIT1): c.410A> G (p.Asp137Gly) single nucleotide variant Pathogenic rs137853139 GRCh37 Chromosome 7, 91865802: 91865802
9 KRIT1 NM_194456.1(KRIT1): c.601C> G (p.Gln201Glu) single nucleotide variant Pathogenic rs137853140 GRCh37 Chromosome 7, 91864845: 91864845
10 KRIT1 KRIT1, 1-BP INS, 1374C insertion Pathogenic
11 KRIT1 NM_194456.1(KRIT1): c.987C> A (p.Cys329Ter) single nucleotide variant Pathogenic rs267607204 GRCh37 Chromosome 7, 91863765: 91863765
12 KRIT1 NM_194456.1(KRIT1): c.715C> T (p.Gln239Ter) single nucleotide variant Pathogenic rs886043300 GRCh37 Chromosome 7, 91864731: 91864731
13 KRIT1 NM_194456.1(KRIT1): c.146_147delGA (p.Arg49Lysfs) deletion Likely pathogenic rs1057518665 GRCh38 Chromosome 7, 92241108: 92241109

Cosmic variations for Cerebral Cavernous Malformations-1:

9
id Cosmic Mut ID Gene Symbol COSMIC Disease Classification
(Primary site, Site subtype, Primary histology, Histology subtype)
Mutation CDS Mutation AA Conf
1 COSM52975 GNAQ soft tissue,blood vessel,other,vascular malformation c.548G>A p.R183Q 5

Expression for Cerebral Cavernous Malformations-1

Search GEO for disease gene expression data for Cerebral Cavernous Malformations-1.

Pathways for Cerebral Cavernous Malformations-1

GO Terms for Cerebral Cavernous Malformations-1

Cellular components related to Cerebral Cavernous Malformations-1 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.36 CCM2 CDKN3 ITGB1BP1 KDR KRIT1 MAP3K3

Biological processes related to Cerebral Cavernous Malformations-1 according to GeneCards Suite gene sharing:

(show all 14)
id Name GO ID Score Top Affiliating Genes
1 positive regulation of cell proliferation GO:0008284 9.73 ITGB1BP1 KDR PDCD10 PTEN
2 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.65 KDR PTEN RAP1A
3 negative regulation of cell proliferation GO:0008285 9.62 CDKN3 ITGB1BP1 PTEN STRN
4 regulation of cyclin-dependent protein serine/threonine kinase activity GO:0000079 9.54 CDKN3 PTEN
5 cellular response to nerve growth factor stimulus GO:1990090 9.52 PTEN RAP1A
6 positive regulation of Notch signaling pathway GO:0045747 9.51 ITGB1BP1 PDCD10
7 endothelial cell migration GO:0043542 9.49 PECAM1 PTEN
8 negative regulation of endothelial cell apoptotic process GO:2000352 9.46 KDR KRIT1
9 positive regulation of focal adhesion assembly GO:0051894 9.4 ITGB1BP1 KDR
10 cellular response to vascular endothelial growth factor stimulus GO:0035924 9.37 ITGB1BP1 KDR
11 negative regulation of focal adhesion assembly GO:0051895 9.26 ITGB1BP1 PTEN
12 negative regulation of cell migration involved in sprouting angiogenesis GO:0090051 9.16 ITGB1BP1 PDCD10
13 positive regulation of vasculogenesis GO:2001214 8.96 KDR RAP1A
14 angiogenesis GO:0001525 8.92 KDR KRIT1 PDCD10 PTEN

Molecular functions related to Cerebral Cavernous Malformations-1 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.73 CCM2 CDKN3 ITGB1BP1 KDR KRIT1 MAP3K3
2 protein complex binding GO:0032403 8.92 ITGB1BP1 KRIT1 RAP1A STRN

Sources for Cerebral Cavernous Malformations-1

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 Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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