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Genetic and Rare Diseases Information Center (GARD)

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Cerebral cavernous malformation


Other Names for this Disease
  • Cavernoma
  • Cavernous angioma
  • CCM
  • Cerebral cavernous hemangioma
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Your Question

My husband had a bleed 20 yrs ago and has multiple cerebral cavernous malformations (CCM). My son had a bleed and was also diagnosed with multiple CCMs.  Does our family need genetic testing?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What are cerebral cavernous malformations (CCMs)?

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.[1]
Last updated: 6/10/2011

What causes cerebral cavernous malformations?

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 create "caverns."  They may not return to their normal size when the blood vessels empty.[1]

Most CCMs are caused by a mutation in one of three particular genes i.e. KRIT1, CCM2, and PDCD10.  The gene mutation may occur for the first time the affected indiviudal (sporadic) or be inherited from a parent (familial).  Acquired CCM can be cause by an injury to the brain or spinal cord. [2]
Last updated: 9/27/2010

What are the signs and symptoms of 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, muscle weakness, loss of sensation, paralysis, hearing or vision deficiencies, and bleeding in the brain (cerebral hemorrhage). Severe brain hemorrhages can result in death.[1] [3] CCM has been reported in infants and children, but the majority of individuals present with symptoms between the second and fifth decades.
Last updated: 9/27/2010

Are cerebral cavernous malformation inherited?

CCMs occur in 0.4-0.5% of the general population.  Cavernous malformations occur in two forms: a "sporadic" form, in which individuals usually present with one or two lesions and no family history of neurologic disease, and the familial form, characterized by multiple lesions and a strong family history of related neurologic deficits. Multiple lesions are thought to be more common in the familial form of CCM.

Individuals with sporadic CCM did not inherit the mutation from a parent.  As mentioned above, they typically have only one or two CCM and have no family members with CCMs.  The CCM developed from a gene mutation that occurred after conception and is not present in all cells of their body.  Those with sporadic CCM do not have a greater chance of having a child with CCM than anyone else in the general population (1 in 200), because the mutation is not located in the reproductive cells. [2]

Familial CCM is inherited in an autosomal dominant manner which means one copy of the altered gene in each cell is sufficient to cause the disorder.  The proportion of familial cases has been estimated to be as high as 50% in Hispanic individuals and 10-40% in Caucasian individuals.[4]  Families with familial CCM typically have (1) multiple lesions on cerebral MRI and (2) several affected individuals in more than one generation.  However, not everyone who has an altered gene for CCM develops symptoms.  The occurrence of CCMs that are not symptomatic may prevent recognition of an autosomal dominant pattern of inheritance in a family.  Additionally, individuals with multiple CCMs may not have a family history of CCM.  In those cases, the mutation could have occured for the first time (de novo mutation) in that individual.[4]

Each child of an individual with familial CCM has a 50% chance of inheriting the mutation. [1] 

Last updated: 9/27/2010

Is genetic testing available for cerebral cavernous malformation (CCM)?

Yes, genetic testing is available for familial cerebral cavernous malformation.  Genetic testing can detect a mutation in one of the three known CCM genes (KRIT1, CCM2 or PDCD10) in 70 percent to 80 percent of individuals from families with CCM. The remaining 20 percent to 30 percent of cases may be due to unidentified genes or to other unknown causes.[1] If no mutation is detected in one of those three genes, research testing may be performed to identify families that demonstrate linkage to a fourth potential location of a CCM gene.[5]

You can find a list of laboratories that provide genetic testing for CCM on the GeneTests Web site.  

Genetic testing can not be performed on a blood sample from someone with sporadic CCM becuase the gene mutation may be located in tissues other than the blood.[2]
Last updated: 12/5/2012

If there are multiple individuals in a family with cerebral cavernous malformations, should family member's at risk consider genetic testing?

Some clinicians recommend an MRI examination at four to five year intervals for asymptomatic adults and children who are known to have a disease-causing mutation identified in an affected family member or who are at risk for CCM based on a family history.  However, lesions that are not symptomatic are rarely treated.  Therefore, the clinical usefulness of such routine screening is yet to be determined. [5]

To learn more about genetic testing for your family, we recommend that you speak with a genetic professional.  Genetics services are a source of information for individuals and families regarding genetic diagnosis, natural history, treatment, mode of inheritance, and genetic risks to other family members. To find a genetics service near you, we recommend that you contact your primary doctor for a referral. Click here to learn more about genetic consultations.

The following online resources can also help you find a genetics professional in your community:

  * GeneTests - A searchable directory of US and international genetics and prenatal diagnosis clinics. Go to the following link and click on 'Clinic Directory' to find a genetic service close to you. http://www.geneclinics.org/

  * ResourceLink - A database of genetics counseling services, searchable by location, name, institution, type of practice, or specialty. Hosted by the National Society of Genetic Counselors.
http://www.nsgc.org/resourcelink.asp

  * Genetic Centers, Clinics, and Departments - A comprehensive resource list for genetic counseling, including links to genetic centers and clinics, associations, and university genetics departments. Hosted by the University of Kansas Medical Center. http://www.kumc.edu/gec/prof/genecntr.html

Last updated: 9/27/2010

References