Cavernous angioma risk factors: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 8: | Line 8: | ||
==Risk Factors== | ==Risk Factors== | ||
* Familial forms of CCM occur at three known genetic loci. | *Familial forms of CCM occur at three known genetic loci. | ||
* The gene for CCM1 encodes ''KRIT1'' (krev interaction trapped 1) and has been found to bind to ICAP1alpha (integrin cytoplasmic domain associated protein alpha), a beta1 [[integrin]] associated protein. <ref name="pmid28387823">{{cite journal| author=Akers A, Al-Shahi Salman R, A Awad I, Dahlem K, Flemming K, Hart B | display-authors=etal| title=Synopsis of Guidelines for the Clinical Management of Cerebral Cavernous Malformations: Consensus Recommendations Based on Systematic Literature Review by the Angioma Alliance Scientific Advisory Board Clinical Experts Panel. | journal=Neurosurgery | year= 2017 | volume= 80 | issue= 5 | pages= 665-680 | pmid=28387823 | doi=10.1093/neuros/nyx091 | pmc=5808153 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28387823 }} </ref> | *The gene for CCM1 encodes ''KRIT1'' (krev interaction trapped 1) and has been found to bind to ICAP1alpha (integrin cytoplasmic domain associated protein alpha), a beta1 [[integrin]] associated protein. <ref name="pmid28387823">{{cite journal| author=Akers A, Al-Shahi Salman R, A Awad I, Dahlem K, Flemming K, Hart B | display-authors=etal| title=Synopsis of Guidelines for the Clinical Management of Cerebral Cavernous Malformations: Consensus Recommendations Based on Systematic Literature Review by the Angioma Alliance Scientific Advisory Board Clinical Experts Panel. | journal=Neurosurgery | year= 2017 | volume= 80 | issue= 5 | pages= 665-680 | pmid=28387823 | doi=10.1093/neuros/nyx091 | pmc=5808153 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28387823 }} </ref> | ||
* The gene for ''CCM2'' encodes MGC4607. <ref name="pmid28387823">{{cite journal| author=Akers A, Al-Shahi Salman R, A Awad I, Dahlem K, Flemming K, Hart B | display-authors=etal| title=Synopsis of Guidelines for the Clinical Management of Cerebral Cavernous Malformations: Consensus Recommendations Based on Systematic Literature Review by the Angioma Alliance Scientific Advisory Board Clinical Experts Panel. | journal=Neurosurgery | year= 2017 | volume= 80 | issue= 5 | pages= 665-680 | pmid=28387823 | doi=10.1093/neuros/nyx091 | pmc=5808153 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28387823 }} </ref>The exact biological function of CCM2 is not clear. Recently, it has been shown that CCM1 and CCM2 proteins as well as ICAP1alpha form a macromolecular complex in the cell. In addition, it appears that CCM2 protein may function as a scaffolding protein for [[MAP kinases]] that are essential in p38 activation responding to osmotic stress including MEKK3 and MKK3. It also binds to [[Rac]] and [[actin]]. Therefore, CCM2 protein is also called OSM (osmosensing scaffold for MEKK3). | *The gene for ''CCM2'' encodes MGC4607. <ref name="pmid28387823">{{cite journal| author=Akers A, Al-Shahi Salman R, A Awad I, Dahlem K, Flemming K, Hart B | display-authors=etal| title=Synopsis of Guidelines for the Clinical Management of Cerebral Cavernous Malformations: Consensus Recommendations Based on Systematic Literature Review by the Angioma Alliance Scientific Advisory Board Clinical Experts Panel. | journal=Neurosurgery | year= 2017 | volume= 80 | issue= 5 | pages= 665-680 | pmid=28387823 | doi=10.1093/neuros/nyx091 | pmc=5808153 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28387823 }} </ref>The exact biological function of CCM2 is not clear. Recently, it has been shown that CCM1 and CCM2 proteins as well as ICAP1alpha form a macromolecular complex in the cell. In addition, it appears that CCM2 protein may function as a scaffolding protein for [[MAP kinases]] that are essential in p38 activation responding to osmotic stress including MEKK3 and MKK3. It also binds to [[Rac]] and [[actin]]. Therefore, CCM2 protein is also called OSM (osmosensing scaffold for MEKK3). | ||
* The ''CCM3'' gene was the most recent CCM gene identified. CCM3 was known as PDCD10 (programmed cell death 10), which was initially identified as a gene that is up-regulated during the induction of [[apoptosis]] (cell death) in TF-1, a human [[myeloid]] cell line. The precise role of the PDCD10 protein in the CCM pathway that has been established to this point has not yet been determined. Research is ongoing to determine the function and properties of all three CCM gene products as well as the reaction pathways in which they are involved.<ref name="pmid28387823">{{cite journal| author=Akers A, Al-Shahi Salman R, A Awad I, Dahlem K, Flemming K, Hart B | display-authors=etal| title=Synopsis of Guidelines for the Clinical Management of Cerebral Cavernous Malformations: Consensus Recommendations Based on Systematic Literature Review by the Angioma Alliance Scientific Advisory Board Clinical Experts Panel. | journal=Neurosurgery | year= 2017 | volume= 80 | issue= 5 | pages= 665-680 | pmid=28387823 | doi=10.1093/ | *The ''CCM3'' gene was the most recent CCM gene identified. CCM3 was known as ''PDCD10'' (programmed cell death 10), which was initially identified as a gene that is up-regulated during the induction of [[apoptosis]] (cell death) in TF-1, a human [[myeloid]] cell line. The precise role of the PDCD10 protein in the CCM pathway that has been established to this point has not yet been determined. Research is ongoing to determine the function and properties of all three CCM gene products as well as the reaction pathways in which they are involved.<ref name="pmid28387823">{{cite journal| author=Akers A, Al-Shahi Salman R, A Awad I, Dahlem K, Flemming K, Hart B | display-authors=etal| title=Synopsis of Guidelines for the Clinical Management of Cerebral Cavernous Malformations: Consensus Recommendations Based on Systematic Literature Review by the Angioma Alliance Scientific Advisory Board Clinical Experts Panel. | journal=Neurosurgery | year= 2017 | volume= 80 | issue= 5 | pages= 665-680 | pmid=28387823 | doi=10.1093/neurons/nyx091 | pmc=5808153 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28387823 }} </ref> | ||
* Mutations in these three genes account for 70 to 80 percent of all cases of cerebral cavernous malformations. The remaining 20 to 30 percent of cases may be due to other, still unidentified, genes. | *Mutations in these three genes account for 70 to 80 percent of all cases of cerebral cavernous malformations. The remaining 20 to 30 percent of cases may be due to other, still unidentified, genes. | ||
== Genetic Testing == | |||
=== Genetic Testing and Counseling Recommendations:<ref name="pmid28387823">{{cite journal| author=Akers A, Al-Shahi Salman R, A Awad I, Dahlem K, Flemming K, Hart B | display-authors=etal| title=Synopsis of Guidelines for the Clinical Management of Cerebral Cavernous Malformations: Consensus Recommendations Based on Systematic Literature Review by the Angioma Alliance Scientific Advisory Board Clinical Experts Panel. | journal=Neurosurgery | year= 2017 | volume= 80 | issue= 5 | pages= 665-680 | pmid=28387823 | doi=10.1093/neuros/nyx091 | pmc=5808153 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28387823 }} </ref> === | |||
# A three-generation family history should be obtained at the time of diagnosis. More focus should be given to symptoms such as headache, stroke, any abnormal MRI scan findings, or other neurological findings. | |||
# In the setting of cavernous angioma without an association of developmental venous anomalies, brain radiation history, or a family history of cavernous angioma, CCM1-3 genes by Sanger or NextGen sequencing followed by duplication/deletion analysis should be considered. | |||
# Counseling the patient and whole family about autosomal dominant inheritance should be done when there is a positive proband. | |||
==References== | ==References== | ||
Revision as of 13:13, 23 February 2022
|
Cavernous angioma Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Cavernous angioma risk factors On the Web |
|
American Roentgen Ray Society Images of Cavernous angioma risk factors |
|
Risk calculators and risk factors for Cavernous angioma risk factors |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Family history increases the risk of having cavernous angioma. Genetic testing is recommended for the pathogenic variants of cavernous angioma (KRIT1, MGC4607, and PDCD10).
Risk Factors
- Familial forms of CCM occur at three known genetic loci.
- The gene for CCM1 encodes KRIT1 (krev interaction trapped 1) and has been found to bind to ICAP1alpha (integrin cytoplasmic domain associated protein alpha), a beta1 integrin associated protein. [1]
- The gene for CCM2 encodes MGC4607. [1]The exact biological function of CCM2 is not clear. Recently, it has been shown that CCM1 and CCM2 proteins as well as ICAP1alpha form a macromolecular complex in the cell. In addition, it appears that CCM2 protein may function as a scaffolding protein for MAP kinases that are essential in p38 activation responding to osmotic stress including MEKK3 and MKK3. It also binds to Rac and actin. Therefore, CCM2 protein is also called OSM (osmosensing scaffold for MEKK3).
- The CCM3 gene was the most recent CCM gene identified. CCM3 was known as PDCD10 (programmed cell death 10), which was initially identified as a gene that is up-regulated during the induction of apoptosis (cell death) in TF-1, a human myeloid cell line. The precise role of the PDCD10 protein in the CCM pathway that has been established to this point has not yet been determined. Research is ongoing to determine the function and properties of all three CCM gene products as well as the reaction pathways in which they are involved.[1]
- Mutations in these three genes account for 70 to 80 percent of all cases of cerebral cavernous malformations. The remaining 20 to 30 percent of cases may be due to other, still unidentified, genes.
Genetic Testing
Genetic Testing and Counseling Recommendations:[1]
- A three-generation family history should be obtained at the time of diagnosis. More focus should be given to symptoms such as headache, stroke, any abnormal MRI scan findings, or other neurological findings.
- In the setting of cavernous angioma without an association of developmental venous anomalies, brain radiation history, or a family history of cavernous angioma, CCM1-3 genes by Sanger or NextGen sequencing followed by duplication/deletion analysis should be considered.
- Counseling the patient and whole family about autosomal dominant inheritance should be done when there is a positive proband.
References
- ↑ 1.0 1.1 1.2 1.3 Akers A, Al-Shahi Salman R, A Awad I, Dahlem K, Flemming K, Hart B; et al. (2017). "Synopsis of Guidelines for the Clinical Management of Cerebral Cavernous Malformations: Consensus Recommendations Based on Systematic Literature Review by the Angioma Alliance Scientific Advisory Board Clinical Experts Panel". Neurosurgery. 80 (5): 665–680. doi:10.1093/neuros/nyx091. PMC 5808153. PMID 28387823.