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Cerebral cavernous malformation

Reviewed November 2006

What is cerebral cavernous malformation?

Cerebral cavernous malformations (CCMs) are collections of small blood vessels (capillaries) in the brain that are enlarged and irregular in structure. These capillaries have abnormally thin walls that are prone to leak. They also lack other support tissues, such as elastic fibers, which normally make them stretchy. As a result, when the capillaries fill with blood, they stretch out and may not return to their normal size when the blood vessels empty. 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).

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). 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, but they do not become cancerous.

How common is cerebral cavernous malformation?

Cerebral cavernous malformations affect about 0.5 percent of the population worldwide.

What genes are related to cerebral cavernous malformation?

Mutations in the CCM2, KRIT1, and PDCD10 genes cause cerebral cavernous malformation.

The precise functions of these genes are not fully understood, but they most likely play a role in blood vessel formation (angiogenesis) during embryonic development. They may also play a role in maintaining existing blood vessels. Researchers have not determined how mutations in these genes can lead to the abnormal capillaries characteristic of cerebral cavernous malformations.

Mutations in these three genes account for 70 percent to 80 percent of all cases of familial cerebral cavernous malformations. The remaining 20 percent to 30 percent of cases may be due to unidentified genes or to other unknown causes.

How do people inherit cerebral cavernous malformation?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent.

Most cases of cerebral cavernous malformation result from a new mutation in the KRIT1, CCM2, or PDCD10 gene. These cases are known as sporadic, and they occur in people with no history of the disorder in their family.

Where can I find information about treatment for cerebral cavernous malformation?

You may find information on treatment or management of cerebral cavernous malformation or some of its symptoms in the links below, particularly the links for Gene Reviews, MedlinePlus Encyclopedia, Educational resources, and Patient support.

Where can I find additional information about cerebral cavernous malformation?

You may find the following resources about cerebral cavernous malformation helpful. These materials are written for the general public.

  • MedlinePlus - Health information
    • Encyclopedia: Cerebral angiography (http://www.nlm.nih.gov/medlineplus/ency/article/003799.htm)
    • Health Topic: Head and Brain Malformations (http://www.nlm.nih.gov/medlineplus/headandbrainmalformations.html)
  • Additional NIH Resources - National Institutes of Health
    National Institute of Neurological Disorders and Stroke (http://www.ninds.nih.gov/disorders/cavernous_malformation/cavernous_malformation.htm)
  • Educational resources - Information pages
    • Children's Hospital Boston (http://www.childrenshospital.org/clinicalservices/Site2162/mainpageS2162P10.html)
    • Johns Hopkins Medicine (http://www.hopkinsneuro.org/disease_and_condition_detail.cfm?condition_id=48)
    • Madisons Foundation (http://www.madisonsfoundation.org/index.php/component/option,com_mpower/diseaseID,391/)
    • Massachusetts General Hospital Neurovascular Center (http://neurosurgery.mgh.harvard.edu/neurovascular/vascintr.htm)
    • Mayo Clinic (http://www.mayoclinic.org/cavernous-malformations/index.html)
    • Orphanet (http://www.orpha.net//consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=164)
    • University of Toronto Brain Vascular Malformation Study Group (http://brainavm.oci.utoronto.ca/malformations/Cavernomas_index.htm)
  • Patient support - For patients and families
    • Angioma Alliance (http://www.angiomaalliance.org/)
    • Genetic Alliance (http://www.geneticalliance.org/ws_display.asp?filter=infosearch_results&info_keyword=Cerebral+Cavernous+Malformation&expand=Treatment)
    • National Organization for Rare Disorders (http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Cavernous+Malformation)
    • The Brain Power Project (http://www.thebrainpowerproject.org/index.html)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=ccm)
  • Gene Tests - DNA tests ordered by healthcare professionals
    • Gene Tests: Familial Cerebral Cavernous Malformation 1 (http://www.genetests.org/query?testid=156867)
    • Gene Tests: Familial Cerebral Cavernous Malformation 2 (http://www.genetests.org/query?testid=156869)
    • Gene Tests: Familial Cerebral Cavernous Malformation 3 (http://www.genetests.org/query?testid=156871)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed&term=(cerebral+cavernous+malformation[TIAB])+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=1800+Days)
  • OMIM - Genetic disorder catalog (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=116860)

What other names do people use for cerebral cavernous malformation?

  • Central Nervous System Cavernous Hemangioma
  • Cerebral Cavernous Hemangioma
  • Familial Cavernous Hemangioma
  • Familial Cavernous Malformation
  • Familial Cerebral Cavernous Angioma
  • Familial Cerebral Cavernous Malformation
  • Intracerebral Cavernous Hemangioma

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about cerebral cavernous malformation?

  • See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
  • Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
  • Submit your question to Ask the Geneticist (http://www.askthegen.org/).

What glossary definitions help with understanding cerebral cavernous malformation?

angiogenesis ; angioma ; autosomal ; autosomal dominant ; capillaries ; cavernous ; cell ; central nervous system ; cerebral hemorrhage ; CNS ; cutaneous ; deficiency ; elastic ; embryonic ; familial ; gene ; hemangioma ; hemorrhage ; malformation ; mutation ; nervous system ; new mutation ; population ; retina ; seizure ; sign ; sporadic ; symptom ; tissue

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References
  • Bergametti F, Denier C, Labauge P, Arnoult M, Boetto S, Clanet M, Coubes P, Echenne B, Ibrahim R, Irthum B, Jacquet G, Lonjon M, Moreau JJ, Neau JP, Parker F, Tremoulet M, Tournier-Lasserve E; Societe Francaise de Neurochirurgie. Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations. Am J Hum Genet. 2005 Jan;76(1):42-51. Epub 2004 Nov 12. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15543491)
  • Dashti SR, Hoffer A, Hu YC, Selman WR. Molecular genetics of familial cerebral cavernous malformations. Neurosurg Focus. 2006 Jul 15;21(1):e2. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16859255)
  • Denier C, Goutagny S, Labauge P, Krivosic V, Arnoult M, Cousin A, Benabid AL, Comoy J, Frerebeau P, Gilbert B, Houtteville JP, Jan M, Lapierre F, Loiseau H, Menei P, Mercier P, Moreau JJ, Nivelon-Chevallier A, Parker F, Redondo AM, Scarabin JM, Tremoulet M, Zerah M, Maciazek J, Tournier-Lasserve E; Societe Francaise de Neurochirurgie. Mutations within the MGC4607 gene cause cerebral cavernous malformations. Am J Hum Genet. 2004 Feb;74(2):326-37. Epub 2004 Jan 22. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14740320)
  • Gault J, Sarin H, Awadallah NA, Shenkar R, Awad IA. Pathobiology of human cerebrovascular malformations: basic mechanisms and clinical relevance. Neurosurgery. 2004 Jul;55(1):1-16; discussion 16-7. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15214969)
  • Labauge P, Krivosic V, Denier C, Tournier-Lasserve E, Gaudric A. Frequency of retinal cavernomas in 60 patients with familial cerebral cavernomas: a clinical and genetic study. Arch Ophthalmol. 2006 Jun;124(6):885-6. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16769843)
  • Marchuk DA, Srinivasan S, Squire TL, Zawistowski JS. Vascular morphogenesis: tales of two syndromes. Hum Mol Genet. 2003 Apr 1;12 Spec No 1:R97-112. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12668602)
  • Plummer NW, Zawistowski JS, Marchuk DA. Genetics of cerebral cavernous malformations. Curr Neurol Neurosci Rep. 2005 Sep;5(5):391-6. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16131422)
  • Sure U, Freman S, Bozinov O, Benes L, Siegel AM, Bertalanffy H. Biological activity of adult cavernous malformations: a study of 56 patients. J Neurosurg. 2005 Feb;102(2):342-7. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15739564)
  • Verlaan DJ, Davenport WJ, Stefan H, Sure U, Siegel AM, Rouleau GA. Cerebral cavernous malformations: mutations in Krit1. Neurology. 2002 Mar 26;58(6):853-7. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11914398)
  • Zawistowski JS, Stalheim L, Uhlik MT, Abell AN, Ancrile BB, Johnson GL, Marchuk DA. CCM1 and CCM2 protein interactions in cell signaling: implications for cerebral cavernous malformations pathogenesis. Hum Mol Genet. 2005 Sep 1;14(17):2521-31. Epub 2005 Jul 21. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16037064)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: November 2006
Published: May 4, 2009