Cavernous angioma risk factors: Difference between revisions

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(/* Genetic Testing and Counseling Recommendations: {{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=1...)
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==Overview==
==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']]').''
[[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]]==
==[[Risk Factors]]==
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*There are three known [[genetic loci]] for [[cavernous angioma]]. These are [[CCM1]], [[CCM2]], and [[CCM3]].
*There are three known [[genetic loci]] for [[cavernous angioma]]. These are [[CCM1]], [[CCM2]], and [[CCM3]].
*[[CCM1]] encodes for [[krev interaction trapped 1]] (''[[KRIT1]]'')  which binds to [[integrin cytoplasmic domain associated protein alpha]] ([[ICAP1alpha|ICAP1-alpha]]), a beta-1 [[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>
*[[CCM1]] encodes for [[krev interaction trapped 1]] (''[[KRIT1]]'')  which binds to [[integrin cytoplasmic domain associated protein alpha]] ([[ICAP1alpha|ICAP1-alpha]]), a beta-1 [[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>
*''[[CCM2]]'' encodes for [[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 nature of [[CCM2]] is still unclear. However, it been proven that there is a [[macromolecular]]complex formed by [[CCM1]] and [[CCM2]] [[proteins]] and [[ICAP1alpha|ICAP1 alpha]] inside the [[cell]]. Also, [[CCM2]] [[protein]] can serve as a [[scaffolding protein]] for [[enzymes]] like [[MAP kinases]] which is essential in [[p38]] [[activation]] responsible for regulation of [[osmotic]] [[stress]] including [[MEKK3]] and [[MKK3]]. It also attaches to [[Rac]] and [[actin]]. Because of these, [[CCM2]] [[protein]] is oftentimes called [[osmosensing scaffold|osmo-sensing scaffold]] ([[OSM]]) for [[MEKK3]].
*''[[CCM2]]'' encodes for [[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 nature of [[CCM2]] is still unclear. However, it has been proven that there is a [[macromolecular]]complex formed by [[CCM1]] and [[CCM2]] [[proteins]] and [[ICAP1alpha|ICAP1 alpha]] inside the [[cell]]. Also, the [[CCM2]] [[protein]] can serve as a [[scaffolding protein]] for [[enzymes]] like [[MAP kinases]] which is essential in [[p38]] [[activation]], responsible for regulation of [[osmotic]] [[stress]] including [[MEKK3]] and [[MKK3]]. It also attaches to [[Rac]] and [[actin]]. Because of these, the [[CCM2]] [[protein]] is oftentimes called [[osmosensing scaffold|osmo-sensing scaffold]] ([[OSM]]) for [[MEKK3]].
*''[[CCM3]]'' [[gene]] is the most recently identified [[CCM gene]]. It was originally known as [[programmed cell death 10]] (''[[PDCD10]]'') , which was thought to be responsible for upregulation of [[apoptosis]] ([[cell death]]) in [[TF-1]], a [[human]] [[myeloid]] [[cell line]]. As of now, the specific role of the [[PDCD10]] [[protein]] and its association with [[CCM3 gene]] is not yet established.<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>
*''[[CCM3]]'' [[gene]] is the most recently identified [[CCM gene]]. It was originally known as [[programmed cell death 10]] (''[[PDCD10]]'') , which was thought to be responsible for upregulation of [[apoptosis]] ([[cell death]]) in [[TF-1]], a [[human]] [[myeloid]] [[cell line]]. As of now, the specific role of the [[PDCD10]] [[protein]] and its association with the [[CCM3 gene]] is not yet established.<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>


*The [[mutations]] in [[CCM1]], [[CCM2]], and [[CCM3]] [[genes]] account for almost 70 to 80 percent of all cases of [[cerebral cavernous malformations]]. The rest has yet to be identified.
*The [[mutations]] in the [[CCM1]], [[CCM2]], and [[CCM3]] [[genes]] account for almost 70 to 80 percent of all cases of [[cerebral cavernous malformations]]. The rest has yet to be identified.


==[[Genetic Testing]]==
==[[Genetic Testing]]==
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*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 [[Magnetic resonance imaging|magnetic resonance]] ([[MRI]]) scan findings, or other [[neurological]] findings.
*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 [[Magnetic resonance imaging|magnetic resonance]] ([[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]], CCM 1-3 [[genes]] by [[Sanger or NextGen sequencing]] followed by [[duplication]]/ [[deletion]] analysis should be considered.
*In the setting of [[cavernous angioma]], without an association of [[developmental venous anomalies]], [[brain radiation]] history, or a [[family history]] of [[cavernous angioma]], CCM 1-3 [[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]].
*[[Counseling]] for the [[patient]] and [[family]] about [[autosomal dominant inheritance]] should be done when there is a positive [[proband]].


==References==
==References==
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[[Category:Genetic disorders]]
[[Category:Genetic disorders]]
[[Category:Dermatology]]
[[Category:Dermatology]]
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Latest revision as of 13:04, 12 May 2022

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Edzel Lorraine Co, D.M.D., M.D.

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

Genetic Testing

Genetic Testing and Counseling Recommendations: [1]

References

  1. 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.