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CCM
MCID: CRB048
MIFTS: 65

Cerebral Cavernous Malformations (CCM)

Categories: Cardiovascular diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Cerebral Cavernous Malformations

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MalaCards integrated aliases for Cerebral Cavernous Malformations:

Name: Cerebral Cavernous Malformations 57 75 55 40
Cerebral Cavernous Malformation 12 75 53 25 54 37 29 6 15
Cerebral Cavernous Malformations 1 74 29 6 72
Cavernous Malformations of Cns and Retina 57 13 6
Familial Cerebral Cavernous Malformation 25 59 72
Cavernous Angiomatous Malformations 57 12 74
Cerebral Capillary Malformations 57 12 74
Ccm 57 53 25
Hyperkeratotic Cutaneous Capillary-Venous Malformations Associated with Cerebral Capillary Malformations 57 6
Hemangioma, Cavernous, Central Nervous System 44 17
Cerebral Cavernous Malformation 1 12 15
Cerebral Cavernous Hemangioma 53 25
Familial Cavernous Angioma 12 74
Cavernous Angioma 53 54
Central Nervous System Cavernous Hemangioma 25
Hereditary Cerebral Cavernous Malformation 59
Cavernous Angiomatous Malformations; Cam 57
Cerebral Cavernous Malformations, Type 1 40
Familial Cerebral Cavernous Angioma 25
Cerebral Cavernous Malformations-1 57
Hereditary Brain Cavernous Angioma 59
Intracerebral Cavernous Hemangioma 25
Cavernous Hemangioma of the Brain 74
Familial Brain Cavernous Angioma 59
Familial Cavernous Malformation 25
Familial Cavernous Hemangioma 25
Hereditary Cerebral Cavernoma 59
Cavernous Angioma, Familial 57
Familial Cerebral Cavernoma 59
Hemangioma, Cavernous 72
Cerebral Cavernoma 74
Angioma, Cavernous 72
Cavernomas 54
Cavernoma 53
Ccm1 74
Cam 57

Characteristics:

Orphanet epidemiological data:

59
familial cerebral cavernous malformation
Inheritance: Autosomal dominant; Prevalence: 1-5/10000 (Worldwide); Age of onset: All ages; Age of death: normal life expectancy;

OMIM:

57
Miscellaneous:
incomplete penetrance
most common age of clinical onset ranges from 16 to 33 years
multiple lesions in familial cases
single lesions in sporadic cases
genetic heterogeneity (ccm2 )

Inheritance:
autosomal dominant


HPO:

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


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Fetal diseases
Anatomical: Neuronal diseases Cardiovascular diseases
See all MalaCards categories (disease lists)
ICD10: 34
Orphanet: 59  
Rare neurological diseases
Rare circulatory system diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0060669 DOID:0080491
OMIM 57 116860
KEGG 37 H00534
MeSH 44 D020786
ICD10 via Orphanet 34 Q28.3
UMLS via Orphanet 73 C2931263
Orphanet 59 ORPHA221061
UMLS 72 C0018920 C1366911 C1959589 more
Sources

Summaries for Cerebral Cavernous Malformations

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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). Approximately 25 percent of individuals with cerebral cavernous malformations never experience any related health problems. Other people with this condition may experience serious signs and symptoms such as headaches, seizures, paralysis, hearing or vision loss, and bleeding in the brain (cerebral hemorrhage). Severe brain hemorrhages can result in death. The location and number of cerebral cavernous malformations determine the severity of this disorder. These malformations can change in size and number over time. There are two forms of the condition: familial and sporadic. The familial form is passed from parent to child, and affected individuals typically have multiple cerebral cavernous malformations. The sporadic form occurs in people with no family history of the disorder. These individuals typically have only one malformation.

MalaCards based summary : Cerebral Cavernous Malformations, also known as cerebral cavernous malformation, is related to cerebral cavernous malformations 3 and cerebral cavernous malformations 2. An important gene associated with Cerebral Cavernous Malformations is KRIT1 (KRIT1 Ankyrin Repeat Containing), and among its related pathways/superpathways are Embryonic and Induced Pluripotent Stem Cell Differentiation Pathways and Lineage-specific Markers and Angiogenesis (CST). The drugs Atorvastatin and Propranolol have been mentioned in the context of this disorder. Affiliated tissues include brain, spinal cord and endothelial, and related phenotypes are seizures and headache

Disease Ontology : 12 A cerebrovascular disease that is characterized by dilated blood-filled capillaries lacking structural support.

NIH Rare Diseases : 53 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.

OMIM : 57 Cerebral cavernous angiomas are relatively rare vascular malformations that may involve any part of the central nervous system. Cerebral cavernous angiomas are to be distinguished from cerebral arteriovenous malformations (106070, 108010). CCMs are venous and not demonstrable by arteriography; hence they are referred to as angiographically silent. Capillary hemangiomas (602089) are classified as distinct from vascular malformations in that hemangiomas are benign, highly proliferative lesions involving aberrant localized growth of capillary endothelium. Hemangiomas develop shortly after birth. In contrast, vascular malformations are present from birth, tend to grow with the individual, do not regress, and show normal rates of endothelial cell turnover (Mulliken and Young, 1988). (116860)

NINDS : 54 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).

KEGG : 37
Cerebral cavernous malformations (CCM) are vascular malformations of the central nervous system comprising enlarged caverns with a single layer of endothelium, which easily lead to cerebral hemorrhages. The disease present as either sporadic or autosomal dominant conditions and is linked to three genes KRIT1, MGC4607, and PDCD10. Mutations in KRIT1 impair its interaction with ICAP-1 alpha, and influence beta 1 integrin-dependent angiogenesis.

UniProtKB/Swiss-Prot : 74 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.

Wikipedia : 75 Cavernous hemangioma, also called cavernous angioma, cavernoma, or cerebral cavernous malformation (CCM)... more...

Sources

Related Diseases for Cerebral Cavernous Malformations

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Diseases in the Cerebral Cavernous Malformations family:

Cerebral Cavernous Malformations 2 Cerebral Cavernous Malformations 3
Cerebral Cavernous Malformation, Familial

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

(show top 50) (show all 787)
# Related Disease Score Top Affiliating Genes
1 cerebral cavernous malformations 3 34.5 PDCD10 MAP3K3 KRIT1 ITGB1BP1 CCM2
2 cerebral cavernous malformations 2 33.1 STK25 STK24 RAP1A PDCD10 MAP3K3 KRIT1
3 cavernous hemangioma 32.3 PECAM1 PDCD10 KRIT1 KDR CCM2
4 venous malformations, multiple cutaneous and mucosal 32.3 PTEN PDCD10 KRIT1 CCM2
5 cavernous malformation 32.3 SERPINI1 PDCD10 MAP3K3 KRIT1 ITGB1BP1 CCM2L
6 klippel-trenaunay-weber syndrome 30.6 PDCD10 KRIT1 CCM2
7 hemangioma 30.1 PTEN PECAM1 KRIT1 KDR CCM2
8 meningioma, familial 29.6 PTEN PDCD10 KLF4
9 cerebral cavernous malformation, familial 12.9
10 dermal unilateral segmental cavernous angioma 12.4
11 cerebrocostomandibular syndrome 12.2
12 cataract 5, multiple types 12.2
13 cerebrofacial arteriovenous metameric syndrome 11.7
14 cobb syndrome 11.6
15 intracranial cavernous angioma 11.5
16 sengers syndrome 11.5
17 cavernous hemangioma of orbit 11.4
18 congenital vascular cavernous malformations 11.4
19 familial hemangioma 11.4
20 vascular erectile tumor 11.4
21 hemangioma, capillary infantile 11.1
22 hepatosplenic t-cell lymphoma 10.9
23 hair whorl 10.9
24 subacute delirium 10.5
25 vascular disease 10.5
26 portal hypertension 10.5
27 cerebrovascular disease 10.4
28 portal vein thrombosis 10.4
29 varicose veins 10.4
30 cell type benign neoplasm 10.4 PDCD10 KRIT1 CCM2
31 hemangioma of orbit 10.3
32 colorectal cancer 10.3
33 arteriovenous malformation 10.3
34 epilepsy 10.3
35 rare surgical neurologic disease 10.3
36 neuroblastoma 1 10.3
37 seizure disorder 10.3
38 obstructive jaundice 10.3
39 aneurysm 10.3
40 suppression amblyopia 10.2
41 amblyopia 10.2
42 back pain 10.2
43 hydrocephalus 10.2
44 visual epilepsy 10.2
45 congenital hydrocephalus 10.2
46 cholestasis 10.2
47 adenocarcinoma 10.2
48 osteoarthritis 10.2
49 papilledema 10.2
50 rare tumor 10.2

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



Diseases related to Cerebral Cavernous Malformations
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Symptoms & Phenotypes for Cerebral Cavernous Malformations

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Human phenotypes related to Cerebral Cavernous Malformations:

59 32 (show all 23)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 59 32 hallmark (90%) Very frequent (99-80%) HP:0001250
2 headache 59 32 hallmark (90%) Very frequent (99-80%) HP:0002315
3 cerebral hemorrhage 59 32 hallmark (90%) Very frequent (99-80%) HP:0001342
4 scoliosis 59 32 frequent (33%) Frequent (79-30%) HP:0002650
5 increased intracranial pressure 59 32 frequent (33%) Frequent (79-30%) HP:0002516
6 meningioma 59 32 frequent (33%) Frequent (79-30%) HP:0002858
7 focal t2 hyperintense brainstem lesion 59 32 frequent (33%) Frequent (79-30%) HP:0012748
8 focal t2 hypointense brainstem lesion 59 32 frequent (33%) Frequent (79-30%) HP:0012749
9 neuroma 59 32 frequent (33%) Frequent (79-30%) HP:0030430
10 vascular skin abnormality 59 32 occasional (7.5%) Occasional (29-5%) HP:0011276
11 cognitive impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0100543
12 spinal cord lesion 59 32 occasional (7.5%) Occasional (29-5%) HP:0100561
13 venous malformation 59 32 occasional (7.5%) Occasional (29-5%) HP:0012721
14 episodic vomiting 59 32 occasional (7.5%) Occasional (29-5%) HP:0002572
15 choroidal hemangioma 59 32 occasional (7.5%) Occasional (29-5%) HP:0007872
16 retinal cavernous angioma 59 32 occasional (7.5%) Occasional (29-5%) HP:0011513
17 cerebral calcification 32 HP:0002514
18 abnormality of the musculature 32 HP:0003011
19 intracranial hemorrhage 32 HP:0002170
20 hemangioma 59 Frequent (79-30%)
21 abnormality of the skin 32 HP:0000951
22 retinal vascular malformation 32 HP:0007797
23 hepatic vascular malformations 32 HP:0006576

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
headache
intracranial hemorrhage
intracranial thin-walled sinusoidal vessel (cavernous) malformations
focal neurologic deficits
more
Head And Neck Eyes:
retinal vascular malformations

Muscle Soft Tissue:
soft tissue vascular malformations

Abdomen Liver:
hepatic vascular malformations

Skin Nails Hair Skin:
hyperkeratotic cutaneous vascular lesions

Clinical features from OMIM:

116860

MGI Mouse Phenotypes related to Cerebral Cavernous Malformations:

46 (show all 11)
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.27 CCM2 CCM2L DLL4 HEG1 KDR KLF2
2 cellular MP:0005384 10.22 CCM2 CCM2L DLL4 HEG1 KDR KLF4
3 growth/size/body region MP:0005378 10.14 CCM2 DLL4 HEG1 ITGB1BP1 KDR KLF2
4 mortality/aging MP:0010768 10.13 CCM2 CCM2L DLL4 HEG1 ITGB1BP1 KDR
5 hematopoietic system MP:0005397 10.11 CCM2 DLL4 KDR KLF2 KLF4 MAP3K3
6 immune system MP:0005387 10.1 CCM2 DLL4 HEG1 KDR KLF2 KLF4
7 embryo MP:0005380 10.09 CCM2 DLL4 HEG1 KDR KLF2 KRIT1
8 craniofacial MP:0005382 10 CCM2 HEG1 ITGB1BP1 KDR KLF2 KLF4
9 muscle MP:0005369 9.9 CCM2 CCM2L DLL4 HEG1 KDR KLF2
10 normal MP:0002873 9.61 CCM2 CCM2L DLL4 ITGB1BP1 KDR KLF2
11 vision/eye MP:0005391 9.23 CCM2 DLL4 ITGB1BP1 KDR KLF4 KRIT1
Sources

Drugs & Therapeutics for Cerebral Cavernous Malformations

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

(show all 27)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Atorvastatin Approved Phase 1, Phase 2 134523-00-5 60823
2
Propranolol Approved, Investigational Phase 2 525-66-6 4946
3 Lipid Regulating Agents Phase 1, Phase 2
4 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 1, Phase 2
5 Hypolipidemic Agents Phase 1, Phase 2
6 Anticholesteremic Agents Phase 1, Phase 2
7 Antimetabolites Phase 1, Phase 2
8 Antihypertensive Agents Phase 2
9 Adrenergic beta-Antagonists Phase 2
10 Neurotransmitter Agents Phase 2
11 Adrenergic Antagonists Phase 2
12 Adrenergic Agents Phase 2
13 Anti-Arrhythmia Agents Phase 2
14 Vasodilator Agents Phase 2
15
Doxycycline Approved, Investigational, Vet_approved Phase 1 564-25-0 54671203
16 Anti-Bacterial Agents Phase 1
17 Antimalarials Phase 1
18 Antiparasitic Agents Phase 1
19 Anti-Infective Agents Phase 1
20 Antiprotozoal Agents Phase 1
21
Simvastatin Approved Early Phase 1 79902-63-9 54454
22 Neuroserpin
23 Astragalus
24 Hematinics
25 Liver Extracts
26 Analgesics
27 Anticonvulsants

Interventional clinical trials:

(show all 14)
# Name Status NCT ID Phase Drugs
1 Phase I-II Randomized, Placebo-Controlled, Single-Blinded, Single-Site Clinical Trial of Atorvastatin in the Treatment of Cavernous Angiomas With Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC) Recruiting NCT02603328 Phase 1, Phase 2 Atorvastatin
2 Effect of Oral Propranolol on mRNA Expression in Symptomatice Caavernous Malformation Recruiting NCT03474614 Phase 2 Propranolol
3 Treat_CCM Clinical Trial A Multicenter Randomized Clinical Trial on Propranolol in Cerebral Cavernous Malformation Recruiting NCT03589014 Phase 2 Propranolol
4 Influence of Matrix Metalloproteinase on Brain Arteriovenous Malformation Hemorrhage Completed NCT00783523 Phase 1 Doxycycline or Placebo
5 Oral Propanolol for Surgically Inaccessible Cerebral and Spinal Cavernous Malformations Enrolling by invitation NCT03523650 Phase 1 Propranolol Oral Tablet;Placebo Oral Tablet
6 A Prospective Study on the Incidence and Related Risk Factors of Infantile Hemangioma in China Unknown status NCT03173352
7 Genetic Disease Gene Identification Unknown status NCT00916903
8 Cerebral Bases Bodily Representations: Imaging Approach by Functional Magnetic Resonance, Cortical Stimulation Corticographie and Surgery Awake Unknown status NCT02876016
9 Permeability MRI in Cerebral Cavernous Malformations Type 1 in New Mexico: Effects of Statins Completed NCT01764451 Early Phase 1 Simvastatin
10 A Prospective Controlled Study on Treatment of Giant Cavernous Hemangiomas of the Liver：RFA Versus Laparoscopic Hepatectomy. Completed NCT01471080
11 CASH (Cavernous Angiomas With Symptomatic Hemorrhage) Trial Readiness Recruiting NCT03652181
12 Modifiers of Disease Severity and Progression in Cerebral Cavernous Malformations Recruiting NCT01764529
13 Treatments and Outcomes of Untreated Cerebral Cavernous Malformations in CHINA (TOUCH): A Nationwide Multicenter Prospective Cohort Study. Recruiting NCT03467295
14 A Prospective Study for the Natural History and the Risk Factors of Prospective Symptomatic Hemorrhage in Adult Patients With Cerebral Cavernous Malformation Recruiting NCT02946866

Search NIH Clinical Center for Cerebral Cavernous Malformations

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

Sources

Genetic Tests for Cerebral Cavernous Malformations

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Genetic tests related to Cerebral Cavernous Malformations:

# Genetic test Affiliating Genes
1 Cerebral Cavernous Malformation 29 KRIT1
2 Cerebral Cavernous Malformations 1 29 KRIT1
Sources

Anatomical Context for Cerebral Cavernous Malformations

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MalaCards organs/tissues related to Cerebral Cavernous Malformations:

41
Brain, Spinal Cord, Endothelial, Retina, Smooth Muscle, Skin, Liver
Sources

Publications for Cerebral Cavernous Malformations

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Articles related to Cerebral Cavernous Malformations:

(show top 50) (show all 762)
# Title Authors PMID Year
1
Cerebral cavernous malformations: mutations in Krit1. 9 38 8 71
11914398 2002
2
CCM1 gene mutations in families segregating cerebral cavernous malformations. 9 38 8 71
11222804 2001
3
C329X in KRIT1 is a founder mutation among CCM patients in Sardinia. 38 8 71
19454328 2009
4
Different spectra of genomic deletions within the CCM genes between Italian and American CCM patient cohorts. 38 8 71
18060436 2008
5
Clinical, magnetic resonance imaging, and genetic study of 5 Italian families with cerebral cavernous malformation. 38 8 71
17562932 2007
6
Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas. 38 8 71
10508515 1999
7
Cerebral cavernous malformations. Incidence and familial occurrence. 38 8 71
3393196 1988
8
KRIT1 is mutated in hyperkeratotic cutaneous capillary-venous malformation associated with cerebral capillary malformation. 8 71
10814716 2000
9
A two-hit mechanism causes cerebral cavernous malformations: complete inactivation of CCM1, CCM2 or CCM3 in affected endothelial cells. 9 38 8
19088124 2009
10
Deletions in CCM2 are a common cause of cerebral cavernous malformations. 9 38 71
17160895 2007
11
CCM1 mutation screen of sporadic cases with cerebral cavernous malformations. 9 38 8
15079030 2004
12
Clinical features of cerebral cavernous malformations patients with KRIT1 mutations. 9 38 8
14755725 2004
13
Mutations within the MGC4607 gene cause cerebral cavernous malformations. 9 38 71
14740320 2004
14
Spectrum and expression analysis of KRIT1 mutations in 121 consecutive and unrelated patients with Cerebral Cavernous Malformations. 9 38 8
12404106 2002
15
Krit1 missense mutations lead to splicing errors in cerebral cavernous malformation. 9 38 71
11941540 2002
16
Germline mutations in the CCM1 gene, encoding Krit1, cause cerebral cavernous malformations. 9 38 71
11310633 2001
17
Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1). 9 38 71
10545614 1999
18
Refined localization of the cerebral cavernous malformation gene (CCM1) to a 4-cM interval of chromosome 7q contained in a well-defined YAC contig. 9 38 8
8750196 1995
19
Endothelial TLR4 and the microbiome drive cerebral cavernous malformations. 38 8
28489816 2017
20
Cerebral cavernous malformations arise from endothelial gain of MEKK3-KLF2/4 signalling. 38 8
27027284 2016
21
EndMT contributes to the onset and progression of cerebral cavernous malformations. 38 8
23748444 2013
22
Untreated clinical course of cerebral cavernous malformations: a prospective, population-based cohort study. 38 71
22297119 2012
23
A founder mutation in the Ashkenazi Jewish population affecting messenger RNA splicing of the CCM2 gene causes cerebral cavernous malformations. 38 71
21543988 2011
24
Biallelic somatic and germline mutations in cerebral cavernous malformations (CCMs): evidence for a two-hit mechanism of CCM pathogenesis. 38 8
19088123 2009
25
Large germline deletions and duplication in isolated cerebral cavernous malformation patients. 38 8
17211633 2007
26
Genotype-phenotype correlations in cerebral cavernous malformations patients. 38 8
17041941 2006
27
Cerebral cavernous malformation: new molecular and clinical insights. 38 8
16571644 2006
28
Value of gradient-echo magnetic resonance imaging in the diagnosis of familial cerebral cavernous malformation. 38 8
15824268 2005
29
Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations. 38 71
15543491 2005
30
Mutations in a gene encoding a novel protein containing a phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations. 38 71
14624391 2003
31
Cerebral Cavernous Malformation, Familial 38 71
20301470 2003
32
Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27. 38 8
9811928 1998
33
A founder mutation as a cause of cerebral cavernous malformation in Hispanic Americans. 38 8
8596595 1996
34
Mapping a gene causing cerebral cavernous malformation to 7q11.2-q21. 38 8
7604043 1995
35
A locus for cerebral cavernous malformations maps to chromosome 7q in two families. 38 8
8530042 1995
36
Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. 71
25355838 2014
37
EFNS guidelines on the molecular diagnosis of channelopathies, epilepsies, migraine, stroke, and dementias. 71
20298421 2010
38
Hemorrhage from cavernous malformations of the brain: definition and reporting standards. Angioma Alliance Scientific Advisory Board. 71
18974380 2008
39
Novel CCM1 mutation in a patient with paraparesis and thoracic cord cavernous malformation. 8
16186553 2005
40
A novel KRIT1/CCM1 truncating mutation in a patient with cerebral and retinal cavernous angiomas. 71
11831930 2002
41
Genetic heterogeneity and absence of founder effect in a series of 36 French cerebral cavernous angiomas families. 8
10352941 1999
42
An association between autosomal dominant cerebral cavernomas and a distinctive hyperkeratotic cutaneous vascular malformation in 4 families. 8
9989629 1999
43
Hereditary cerebral cavernous angiomas: clinical and genetic features in 57 French families. Société Française de Neurochirurgie. 8
9863787 1998
44
Cutaneous and cerebral haemangiomas associated with eruptive angiokeratomas. 8
8776368 1996
45
A gene responsible for cavernous malformations of the brain maps to chromosome 7q. 8
7795602 1995
46
Familial cerebral cavernous angiomas: clinical and radiologic studies. 71
7898703 1995
47
Familial cerebral, hepatic, and retinal cavernous angiomas: a new syndrome. 8
7923228 1994
48
Cavernous angiomatosis of the central nervous system: usefulness of screening the family. 8
8256569 1993
49
Familial cavernous angiomas of the brain: observations in a four generation family. 8
1468464 1992
50
Terminal transverse limb defects associated with familial cavernous angiomatosis. 8
1536177 1992
Sources

Variations for Cerebral Cavernous Malformations

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ClinVar genetic disease variations for Cerebral Cavernous Malformations:

6 (show top 50) (show all 136)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 KRIT1 NM_194456.1(KRIT1): c.729+2T> C single nucleotide variant Pathogenic rs1554528541 7:91864715-91864715 7:92235401-92235401
2 KRIT1 NM_194456.1(KRIT1): c.1144dup (p.Arg382fs) duplication Pathogenic rs1554518386 7:91855842-91855842 7:92226528-92226528
3 KRIT1 NM_194456.1(KRIT1): c.1197_1200CAAA[1] (p.Gln401fs) short repeat Pathogenic rs1057517753 7:91855084-91855087 7:92225770-92225773
4 KRIT1 NM_194456.1(KRIT1): c.1890G> A (p.Trp630Ter) single nucleotide variant Pathogenic rs1554503009 7:91842644-91842644 7:92213330-92213330
5 KRIT1 NM_194456.1(KRIT1): c.1356_1357TC[3] (p.Gln455fs) short repeat Pathogenic rs1180476377 7:91852184-91852185 7:92222870-92222871
6 KRIT1 NM_194456.1(KRIT1): c.1201C> T (p.Gln401Ter) single nucleotide variant Pathogenic rs1331502949 7:91855087-91855087 7:92225773-92225773
7 KRIT1 NM_194456.1(KRIT1): c.730-2A> G single nucleotide variant Pathogenic rs1554527925 7:91864239-91864239 7:92234925-92234925
8 KRIT1 NM_194456.1(KRIT1): c.782C> G (p.Ser261Ter) single nucleotide variant Pathogenic rs1554527817 7:91864185-91864185 7:92234871-92234871
9 KRIT1 KRIT1, 1283C-T single nucleotide variant Pathogenic
10 KRIT1 KRIT1, 1-BP DEL, 1342A deletion Pathogenic
11 KRIT1 KRIT1, 1-BP INS, 1271C insertion Pathogenic
12 KRIT1 NM_194456.1(KRIT1): c.1363C> T (p.Gln455Ter) single nucleotide variant Pathogenic rs267607203 7:91852184-91852184 7:92222870-92222870
13 KRIT1 KRIT1, 1-BP DEL, 103G deletion Pathogenic
14 KRIT1 KRIT1, IVS2DS, T-C, +2 single nucleotide variant Pathogenic
15 KRIT1 KRIT1, 2-BP DEL, 741TC deletion Pathogenic
16 KRIT1 NM_194456.1(KRIT1): c.410A> G (p.Asp137Gly) single nucleotide variant Pathogenic rs137853139 7:91865802-91865802 7:92236488-92236488
17 KRIT1 NM_194456.1(KRIT1): c.601C> G (p.Gln201Glu) single nucleotide variant Pathogenic rs137853140 7:91864845-91864845 7:92235531-92235531
18 KRIT1 KRIT1, 1-BP INS, 1374C insertion Pathogenic
19 KRIT1 NM_194456.1(KRIT1): c.987C> A (p.Cys329Ter) single nucleotide variant Pathogenic rs267607204 7:91863765-91863765 7:92234451-92234451
20 KRIT1 NM_194456.1(KRIT1): c.1267C> T (p.Arg423Ter) single nucleotide variant Pathogenic rs886039402 7:91852280-91852280 7:92222966-92222966
21 KRIT1 NM_194456.1(KRIT1): c.152_155del (p.Lys51fs) deletion Pathogenic rs886039400 7:91870414-91870417 7:92241100-92241103
22 KRIT1 NM_194456.1(KRIT1): c.1400C> A (p.Ser467Ter) single nucleotide variant Pathogenic rs1554513911 7:91852147-91852147 7:92222833-92222833
23 KRIT1 NM_194456.1(KRIT1): c.2119_2120del (p.Ser707fs) deletion Pathogenic rs1554490317 7:91830643-91830644 7:92201329-92201330
24 KRIT1 NM_194456.1(KRIT1): c.196C> T (p.Gln66Ter) single nucleotide variant Pathogenic rs771656368 7:91870373-91870373 7:92241059-92241059
25 KRIT1 NM_194456.1(KRIT1): c.972_975CATT[3] (p.Tyr327fs) short repeat Pathogenic rs1326827713 7:91863773-91863776 7:92234459-92234462
26 KRIT1 NM_194456.1(KRIT1): c.1437_1438del (p.Lys479fs) deletion Pathogenic 7:91851341-91851342 7:92222027-92222028
27 KRIT1 NM_194456.1(KRIT1): c.1373del (p.Gln458fs) deletion Pathogenic 7:91852174-91852174 7:92222860-92222860
28 KRIT1 NM_194456.1(KRIT1): c.1199_1203AACAA[1] (p.Asn402fs) short repeat Pathogenic 7:91855080-91855084 7:92225766-92225770
29 KRIT1 NM_194456.1(KRIT1): c.1301_1305TTGAA[1] (p.Leu436fs) short repeat Pathogenic 7:91852237-91852241 7:92222923-92222927
30 KRIT1 NM_194456.1(KRIT1): c.268C> T (p.Arg90Ter) single nucleotide variant Pathogenic 7:91867068-91867068 7:92237754-92237754
31 KRIT1 NC_000007.13: g.(?_91855014)_(91856016_?)del deletion Pathogenic 7:91855014-91856016 7:92225700-92226702
32 KRIT1 NM_194456.1(KRIT1): c.1255-1_1256delGTA deletion Pathogenic rs1554514380 7:91852291-91852293 7:92222977-92222979
33 KRIT1 NM_194456.1(KRIT1): c.1412-1G> T single nucleotide variant Pathogenic rs1554513070 7:91851368-91851368 7:92222054-92222054
34 KRIT1 NM_194456.1(KRIT1): c.1545del (p.Leu516fs) deletion Pathogenic rs1554512658 7:91851234-91851234 7:92221920-92221920
35 KRIT1 NM_194456.1(KRIT1): c.1683_1695del (p.Val562fs) deletion Pathogenic rs1554504519 7:91843960-91843972 7:92214646-92214658
36 KRIT1 NM_194456.1(KRIT1): c.812G> A (p.Trp271Ter) single nucleotide variant Pathogenic rs1554527779 7:91864155-91864155 7:92234841-92234841
37 KRIT1 NM_194456.1(KRIT1): c.990G> A (p.Trp330Ter) single nucleotide variant Pathogenic rs1554518783 7:91855996-91855996 7:92226682-92226682
38 KRIT1 NM_194456.1(KRIT1): c.1417C> T (p.Gln473Ter) single nucleotide variant Pathogenic rs1554513061 7:91851362-91851362 7:92222048-92222048
39 KRIT1 NM_194456.1(KRIT1): c.1700_1701AG[1] (p.Glu567_Ser568insTer) short repeat Pathogenic rs1554504484 7:91843952-91843953 7:92214638-92214639
40 KRIT1 deletion Pathogenic
41 KRIT1 NC_000007.13: g.(?_91829918)_(91871469_?)del deletion Pathogenic 7:91829918-91871469 7:92200604-92242155
42 KRIT1 NC_000007.13: g.(?_91870287)_(91871469_?)del deletion Pathogenic 7:91870287-91871469 7:92240973-92242155
43 KRIT1 NC_000007.13: g.(?_91863763)_(91871451_?)del deletion Pathogenic 7:91863763-91871451 :0-0
44 KRIT1 NM_194456.1(KRIT1): c.659dup (p.Leu220fs) duplication Pathogenic 7:91864787-91864787 7:92235474-92235474
45 KRIT1 NM_194456.1(KRIT1): c.747_750del (p.Asn250fs) deletion Pathogenic 7:91864217-91864220 7:92234906-92234909
46 KRIT1 NM_194456.1(KRIT1): c.810dup (p.Trp271fs) duplication Pathogenic 7:91864157-91864157 7:92234847-92234847
47 KRIT1 NM_194456.1(KRIT1): c.1342del (p.Met448fs) deletion Pathogenic 7:91852205-91852205 7:92222892-92222892
48 KRIT1 NM_194456.1(KRIT1): c.1558A> T (p.Lys520Ter) single nucleotide variant Pathogenic 7:91851221-91851221 7:92221907-92221907
49 KRIT1 NM_194456.1(KRIT1): c.1742_1748dup (p.Ile584fs) duplication Pathogenic 7:91843275-91843276 7:92213968-92213974
50 KRIT1 NM_194456.1(KRIT1): c.730-1G> C single nucleotide variant Pathogenic/Likely pathogenic rs1554527922 7:91864238-91864238 7:92234924-92234924

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

74
# Symbol AA change Variation ID SNP ID
1 KRIT1 p.Phe97Ser VAR_023573
2 KRIT1 p.Lys569Glu VAR_023574

Sources

Expression for Cerebral Cavernous Malformations

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Search GEO for disease gene expression data for Cerebral Cavernous Malformations.
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Pathways for Cerebral Cavernous Malformations

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Pathways related to Cerebral Cavernous Malformations according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Embryonic and Induced Pluripotent Stem Cell Differentiation Pathways and Lineage-specific Markers 65
11.26 KLF4 KLF2 KDR
2
Angiogenesis (CST) 4
10.75 PECAM1 KDR DLL4
Sources

GO Terms for Cerebral Cavernous Malformations

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

(show all 37)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of gene expression GO:0010629 9.94 PDCD10 KLF4 KDR DLL4
2 negative regulation of cell migration GO:0030336 9.85 STK24 PTEN KLF4
3 protein autophosphorylation GO:0046777 9.85 STK25 STK24 MAP3K3 KDR
4 activation of protein kinase activity GO:0032147 9.83 STK25 STK24 MAP3K3
5 multicellular organism growth GO:0035264 9.82 KLF2 HEG1 CCM2
6 negative regulation of ERK1 and ERK2 cascade GO:0070373 9.8 PTEN KLF4 ITGB1BP1
7 cellular response to organic cyclic compound GO:0071407 9.79 RAP1A KLF4 KLF2
8 vasculogenesis GO:0001570 9.75 KDR HEG1 CCM2
9 signal transduction by protein phosphorylation GO:0023014 9.74 STK25 STK24 MAP3K3
10 response to hydrogen peroxide GO:0042542 9.73 STK25 STK24 PDCD10
11 stress-activated protein kinase signaling cascade GO:0031098 9.71 STK25 STK24 MAP3K3
12 positive regulation of Notch signaling pathway GO:0045747 9.7 PDCD10 ITGB1BP1 DLL4
13 negative regulation of endothelial cell migration GO:0010596 9.67 KRIT1 DLL4
14 positive regulation of stress-activated MAPK cascade GO:0032874 9.67 STK25 PDCD10
15 negative regulation of focal adhesion assembly GO:0051895 9.66 PTEN ITGB1BP1
16 negative regulation of phosphatidylinositol 3-kinase signaling GO:0014067 9.66 PTEN KLF4
17 cellular response to peptide GO:1901653 9.65 KLF4 KLF2
18 endothelial cell morphogenesis GO:0001886 9.65 PECAM1 HEG1
19 positive regulation of vasculogenesis GO:2001214 9.63 RAP1A KDR
20 positive regulation of protein metabolic process GO:0051247 9.63 KLF4 KLF2
21 angiogenesis GO:0001525 9.63 PTEN PECAM1 PDCD10 KRIT1 KDR DLL4
22 pericardium development GO:0060039 9.62 HEG1 CCM2
23 cellular response to vascular endothelial growth factor stimulus GO:0035924 9.61 KDR ITGB1BP1 DLL4
24 establishment of Golgi localization GO:0051683 9.6 STK25 PDCD10
25 cellular response to laminar fluid shear stress GO:0071499 9.59 KLF4 KLF2
26 venous blood vessel morphogenesis GO:0048845 9.58 HEG1 CCM2
27 negative regulation of cell migration involved in sprouting angiogenesis GO:0090051 9.56 PDCD10 KLF4 ITGB1BP1 DLL4
28 positive regulation of fibroblast growth factor production GO:0090271 9.51 HEG1 CCM2L
29 ventricular trabecula myocardium morphogenesis GO:0003222 9.5 HEG1 DLL4 CCM2L
30 Golgi reassembly GO:0090168 9.49 STK25 PDCD10
31 endothelial cell development GO:0001885 9.48 HEG1 CCM2
32 cellular response to cycloheximide GO:0071409 9.46 KLF4 KLF2
33 intrinsic apoptotic signaling pathway in response to hydrogen peroxide GO:0036481 9.4 STK25 PDCD10
34 cardiac muscle tissue growth GO:0055017 9.37 HEG1 CCM2L
35 regulation of axon regeneration GO:0048679 9.13 STK24 PTEN KLF4
36 cardiac atrium morphogenesis GO:0003209 8.8 HEG1 DLL4 CCM2L
37 negative regulation of cell proliferation GO:0008285 10 PTEN KLF4 ITGB1BP1 DLL4 CDKN3

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

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.53 STK25 STK24 RAP1A PTEN PECAM1 PDCD10
Sources

Sources for Cerebral Cavernous Malformations

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3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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