Cerebral Cavernous Malformation, Familial

Categories: Cardiovascular diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Cerebral Cavernous Malformation, Familial

MalaCards integrated aliases for Cerebral Cavernous Malformation, Familial:

Name: Cerebral Cavernous Malformation, Familial 24
Familial Cerebral Cavernous Malformation 24 52 71
Hereditary Cerebral Cavernous Malformation 52
Hereditary Brain Cavernous Hemangioma 52
Familial Cerebral Cavernous Angioma 24
Familial Brain Cavernous Hemangioma 52
Hereditary Brain Cavernous Angioma 52
Familial Brain Cavernous Angioma 52
Familial Cavernous Hemangioma 24
Hereditary Cerebral Cavernoma 52
Familial Cerebral Cavernoma 52



Penetrance Krit1. among 64 families with 202 individuals who were heterozygous for a krit1 pathogenic variant [denier et al 2004b]:...


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UMLS 71 C2931263

Summaries for Cerebral Cavernous Malformation, Familial

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 221061 Definition A rare, capillary-venous malformations characterized by closely clustered irregular dilated capillaries that can be asymptomatic or that can cause variable neurological manifestations such as seizures , non-specific headaches, progressive or transient focal neurologic deficits, and/or cerebral hemorrhages. Epidemiology The overall prevalence of all CCMs has been estimated at 1/200 to 1/1,000 individuals. Familial cerebral cavernous malformation (FCCM) represents about 20% of all CCM cases with an estimated prevalence of 1/5,000 -1/10,000 and is therefore rare, contrarily to sporadic CCMs which are not. A strong founder effect has been found in Hispanic-American CCM families. Clinical description Close to 60% of FCCM patients are symptomatic. FCCM usually manifests between 20 to 30 years of age, but clinical manifestations can occur at any age. Symptoms include seizures (40-70%), non-specific headaches (10-30%), progressive or transient focal neurologic deficits (35-50%), and/or cerebral hemorrhages (41%). FCCM patients most often present with multiple lesions, ranging from a few millimeters to a few centimeters in size. FCCMs occur predominantly in the brain, but have also been reported in the spinal cord, retina (5% of FCCM patients) and skin. Etiology To date, mutations in three genes have been demonstrated to cause familial CCM; KRIT1 , CCM2 and PDCD10 , located on chromosome 7q21.2, 7p13, and 3q26.1 respectively, which encode proteins that, among their various functions, modulate junction formation between vascular endothelial cells . Diagnostic methods Cerebral magnetic resonance imaging (MRI) revealing the CCM(s) is the gold standard investigation to diagnose CCM and should include a T2 gradient echo sequence which is highly sensitive for hemosiderin. MRI shows multiple lesions in most FCCM patients in contrast with sporadic cases who harbor only one lesion. The detection of multiple CCM lesions is therefore strongly suggestive of the genetic nature of the disease. Molecular screening of FCCM genes is sometimes useful to ascertain the diagnosis in patients showing atypical MRI lesions; however, in most cases, it is used for genetic counseling . Differential diagnosis In cases presenting with atypical hemorrhagic MRI lesions, the differential diagnosis of FCCM includes multiple hemorrhagic metastases or hereditary cerebral hemorrhage with amyloidosis. Antenatal diagnosis Prenatal diagnosis is possible. However, in practice, very few prenatal diagnoses are requested in this disease (mostly in families where several patients have been severely affected with CCMs in the basal ganglia or spinal cord or pons). Genetic counseling FCCM is transmitted as an autosomal dominant trait with incomplete penetrance . Genetic counseling should be offered to the affected families informing them of the 50% risk of inheriting the mutated gene. Other important considerations in evaluating the genetic predisposition of CCMs include the number of lesions on the MRI brain scan, family history of CCM clinical characteristics, and the age of onset. Management and treatment Regular check-ups, generally with an MRI once a year, are recommended after the discovery of a CCM, as additional asymptomatic lesions may appear with time. These MRI check-ups can be spaced to once every 5 years in the absence of intercurrent symptoms. Treatment of seizures and headaches is symptomatic. Lesions causing severe disabling seizures and/or focal neurologic deficits and/or cerebral hemorrhages call for surgical removal of lesions whenever possible. Acetylsalicylic acid, heparin and warfarin may increase the risk of hemorrhage. Prognosis FCCM is an evolving condition with a strong correlation between the patient's age and the number of CCM lesions. The hemorrhagic event rate is estimated at 2-5% per lesion per year. Functional outcome is mostly conditioned by the location of CCM lesions, with brainstem and basal ganglia lesions having a worse prognosis. Available data suggest that in most patients the long-term prognosis is quite favorable with a preserved autonomy in 80% of cases. Visit the Orphanet disease page for more resources.

MalaCards based summary : Cerebral Cavernous Malformation, Familial, also known as familial cerebral cavernous malformation, is related to cerebral cavernous malformations and cavernous malformation. An important gene associated with Cerebral Cavernous Malformation, Familial is KRIT1 (KRIT1 Ankyrin Repeat Containing). Affiliated tissues include brain, endothelial and spinal cord, and related phenotypes are embryo and integument

GeneReviews: NBK1293

Related Diseases for Cerebral Cavernous Malformation, Familial

Diseases in the Cerebral Cavernous Malformations family:

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

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

(show all 33)
# Related Disease Score Top Affiliating Genes
1 cerebral cavernous malformations 31.9 PDCD10 KRIT1 CCM2
2 cavernous malformation 29.1 PDCD10 KRIT1 CCM2
3 cavernous hemangioma 29.0 PDCD10 KRIT1 CCM2
4 hemangioma 28.9 PDCD10 KRIT1 CCM2
5 cerebral cavernous malformations 2 28.9 PDCD10 KRIT1 CCM2
6 cerebral angioma 28.7 PDCD10 KRIT1 CCM2
7 cerebral cavernous malformations 3 28.7 PDCD10 KRIT1 CCM2
8 vascular disease 28.1 PDCD10 KRIT1 CCM2
9 myasthenic syndrome, congenital, 1b, fast-channel 10.1
10 aphasia 10.0
11 hemiplegia 10.0
12 pseudobulbar palsy 10.0
13 oncocytoma 9.9
14 myasthenic syndrome, congenital, 1a, slow-channel 9.9
15 retinal vascular disease 9.9
16 spastic paraparesis 9.9
17 headache 9.9
18 seizure disorder 9.9
19 cysticercosis 9.9
20 intracranial cysts 9.9
21 sturge-weber syndrome 9.9
22 von hippel-lindau syndrome 9.9
23 arteriovenous malformation 9.9
24 retinal hemangioblastoma 9.9
25 hemangioblastoma 9.9
26 weber syndrome 9.9
27 wyburn-mason syndrome 9.9
28 hemangioma of liver 9.4 KRIT1 CCM2
29 poland syndrome 9.4 PDCD10 CCM2
30 brain angioma 9.2 PDCD10 KRIT1 CCM2
31 venous malformations, multiple cutaneous and mucosal 9.2 PDCD10 KRIT1 CCM2
32 klippel-trenaunay-weber syndrome 9.1 PDCD10 KRIT1 CCM2
33 hemorrhagic disease 9.0 PDCD10 KRIT1 CCM2

Graphical network of the top 20 diseases related to Cerebral Cavernous Malformation, Familial:

Diseases related to Cerebral Cavernous Malformation, Familial

Symptoms & Phenotypes for Cerebral Cavernous Malformation, Familial

MGI Mouse Phenotypes related to Cerebral Cavernous Malformation, Familial:

# Description MGI Source Accession Score Top Affiliating Genes
1 embryo MP:0005380 9.43 CCM2 KRIT1 PDCD10
2 integument MP:0010771 9.33 CCM2 KRIT1 PDCD10
3 muscle MP:0005369 9.13 CCM2 KRIT1 PDCD10
4 vision/eye MP:0005391 8.8 CCM2 KRIT1 PDCD10

Drugs & Therapeutics for Cerebral Cavernous Malformation, Familial

Search Clinical Trials , NIH Clinical Center for Cerebral Cavernous Malformation, Familial

Genetic Tests for Cerebral Cavernous Malformation, Familial

Anatomical Context for Cerebral Cavernous Malformation, Familial

MalaCards organs/tissues related to Cerebral Cavernous Malformation, Familial:

Brain, Endothelial, Spinal Cord, Retina, Skin, Pons, Cortex

Publications for Cerebral Cavernous Malformation, Familial

Articles related to Cerebral Cavernous Malformation, Familial:

(show top 50) (show all 159)
# Title Authors PMID Year
Loss of CCM3 impairs DLL4-Notch signalling: implication in endothelial angiogenesis and in inherited cerebral cavernous malformations. 61 24
23388056 2013
Vertebral and spinal cavernous angiomas associated with familial cerebral cavernous malformation. 61 24
18207546 2009
Cerebral cavernous malformation: novel mutation in a Chinese family and evidence for heterogeneity. 61 24
11959162 2002
CCM3/PDCD10 gene mutation in cerebral cavernous malformations associated with hyperkeratotic cutaneous capillary venous malformations. 24
26896283 2016
Medical management of epileptic seizures: challenges and solutions. 24
26966367 2016
Prospective Hemorrhage Rates of Cerebral Cavernous Malformations in Children and Adolescents Based on MRI Appearance. 24
26272978 2015
Defective autophagy is a key feature of cerebral cavernous malformations. 24
26417067 2015
Pathological Evaluation of Radiation-Induced Vascular Lesions of the Brain: Distinct from De Novo Cavernous Hemangioma. 24
26446658 2015
Structure and vascular function of MEKK3-cerebral cavernous malformations 2 complex. 24
26235885 2015
Sulindac metabolites decrease cerebrovascular malformations in CCM3-knockout mice. 24
26109568 2015
Exceptional aggressiveness of cerebral cavernous malformation disease associated with PDCD10 mutations. 24
25122144 2015
Sensitivity of patients with familial cerebral cavernous malformations to therapeutic radiation. 24
25565562 2015
Strategy for identifying repurposed drugs for the treatment of cerebral cavernous malformation. 24
25486933 2015
Radiosurgery for symptomatic cavernous malformations: A multi-institutional retrospective study in Japan. 24
26005588 2015
KRIT1 protein depletion modifies endothelial cell behavior via increased vascular endothelial growth factor (VEGF) signaling. 24
25320085 2014
CCM proteins control endothelial β1 integrin dependent response to shear stress. 24
25432514 2014
Surgical outcomes and natural history of intramedullary spinal cord cavernous malformations: a single-center series and meta-analysis of individual patient data: Clinic article. 24
25062285 2014
Mystery Case: Cutaneous lesions in KRIT1-associated cerebral cavernous malformations. 24
25267988 2014
Outcome after surgical or conservative management of cerebral cavernous malformations. 24
24994841 2014
A novel CCM1 mutation associated with multiple cerebral and vertebral cavernous malformations. 24
25086949 2014
Safety of thrombolysis in patients with acute ischemic stroke and cerebral cavernous malformations. 24
24788970 2014
High mutation detection rates in cerebral cavernous malformation upon stringent inclusion criteria: one-third of probands are minors. 24
24689081 2014
KRIT1 loss of function causes a ROS-dependent upregulation of c-Jun. 24
24291398 2014
Symptomatic cerebral cavernomas in pregnancy: a series of 6 cases and review of the literature. 24
23718734 2014
PDCD10 gene mutations in multiple cerebral cavernous malformations. 24
25354366 2014
The value of susceptibility weighted magnetic resonance imaging in evaluation of patients with familial cerebral cavernous angioma. 24
25664034 2014
Natural history of cerebral dot-like cavernomas. 24
23663874 2013
EndMT contributes to the onset and progression of cerebral cavernous malformations. 24
23748444 2013
Cerebral cavernous malformations: from CCM genes to endothelial cell homeostasis. 24
23506982 2013
CCM3 Mutations Are Associated with Early-Onset Cerebral Hemorrhage and Multiple Meningiomas. 24
23801932 2013
Progressive late-onset of cutaneous angiomatosis as possible sign of cerebral cavernous malformations. 24
23473272 2013
Use of antithrombotic agents in patients with intracerebral cavernous malformations. 24
22998055 2013
Risk for symptomatic hemorrhage of cerebral cavernous malformations during pregnancy. 24
23039155 2013
Cavernous malformations in pregnancy. 24
23979052 2013
Antithrombotic therapy and bleeding risk in a prospective cohort study of patients with cerebral cavernous malformations. 24
23150651 2012
Decreased Krev interaction-trapped 1 expression leads to increased vascular permeability and modifies inflammatory responses in vivo. 24
22922958 2012
Cerebral cavernous malformations and pregnancy: hemorrhage risk and influence on obstetrical management. 24
22710379 2012
[Obstetric anaesthesia in two patients with cerebral cavernomas: about two cases]. 24
22749550 2012
Fasudil decreases lesion burden in a murine model of cerebral cavernous malformation disease. 24
22034008 2012
Natural history and imaging prevalence of cavernous malformations in children and young adults. 24
22295927 2012
Neurocutaneous syndromes. 24
22939051 2012
A founder mutation in the Ashkenazi Jewish population affecting messenger RNA splicing of the CCM2 gene causes cerebral cavernous malformations. 24
21543988 2011
Mutation analysis of CCM1, CCM2 and CCM3 genes in a cohort of Italian patients with cerebral cavernous malformation. 24
21029238 2011
An intriguing co-existence: atrial myxoma and cerebral cavernous malformations: case report and review of literature. 24
20650606 2011
Cavernous malformations of the brainstem presenting in childhood: surgical experience in 40 patients. 24
21107189 2010
Stereotactic radiosurgery for the treatment of symptomatic brainstem cavernous malformations. 24
20809752 2010
Cerebral cavernous malformation protein CCM1 inhibits sprouting angiogenesis by activating DELTA-NOTCH signaling. 24
20616044 2010
KRIT1 regulates the homeostasis of intracellular reactive oxygen species. 24
20668652 2010
Radiosurgery in cavernous malformations: anatomy of a controversy. 24
20170301 2010
Gamma knife radiosurgery for intracranial cavernous malformations. 24
20371149 2010

Variations for Cerebral Cavernous Malformation, Familial

Expression for Cerebral Cavernous Malformation, Familial

Search GEO for disease gene expression data for Cerebral Cavernous Malformation, Familial.

Pathways for Cerebral Cavernous Malformation, Familial

GO Terms for Cerebral Cavernous Malformation, Familial

Biological processes related to Cerebral Cavernous Malformation, Familial according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 angiogenesis GO:0001525 8.62 PDCD10 KRIT1

Sources for Cerebral Cavernous Malformation, Familial

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
54 Novoseek
57 OMIM via Orphanet
61 PubMed
70 Tocris
72 UMLS via Orphanet
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