Clinical Testing for Genetic Mutations
Genetic testing is most likely to identify mutations in individuals who have either:
- multiple CCMs that can’t be explained by a developmental venous anomaly (also known as DVA or venous angioma) or by a history of brain or spinal radiation.
- People can have multiple CCMs caused by radiation therapy to treat brain cancer. In these cases, it is very unlikely that the person has familial CCM.
- People can also have multiple CCMs associated with a developmental venous anomaly (DVA; venous angioma). DVAs are not hereditary, making it unlikely that a person has familial CCM.
- at least one CCM and additional family member(s) with CCMs
The standard strategy for genetic testing includes sequencing and deletion/duplication studies of KRIT1 (CCM1), CCM2, and PDCD10 (CCM3).
For people of Hispanic ancestry of Mexican descent or descendants of the original Spanish settlers of the American Southwest, testing may start with the KRIT1 c.1363C>T (p.Q455*) founder mutation. If negative for KRIT1 c.1363C>T (p.Q455*), the person should then have comprehensive genetic testing of all three CCM genes.
Clinical vs Research Testing
Testing for genetic mutations may be for research or clinical purposes. Only clinical testing can be used to officially diagnose a genetic mutation because it is subject to strict regulations and quality control standards.
Testing done as part of a research study cannot be used to make a formal diagnosis. If a research test suggests a possible mutation, the result must be confirmed through clinical testing before it is considered official. For this reason, specific research results are usually not shared with study participants. Instead, participants may be advised to pursue clinical testing.
Where to Have Testing
There are multiple labs in the United States, listed below, that offer CCM genetic testing:
For all clinical diagnostic CCM testing, a doctor must be involved. If you have any questions or concerns about genetic testing for familial CCM, we encourage you to speak with a healthcare provider. Your local provider (neurologist, neurosurgeon, or primary care doctor) may refer you to medical genetics. A genetics professional can help you understand the chances that you have familial CCM, coordinate genetic testing, and help you understand your results and next steps.
Direct-to-consumer products like those offered by 23andMe or AncestryDNA do not include comprehensive genetic testing of KRIT1, CCM2, and PDCD10.
Genetic Testing Results
- Approximately 85-95% of patients with multiple CCMs will have a positive genetic test result for KRIT1 (CCM1), CCM2, or PDCD10 (CCM3), which explains their diagnosis.
- If a positive genetic testing result is identified, it can make it affordable for your family to be screened for the mutation.
- Rather than going through an MRI, other family members can have targeted genetic testing for just the positive test result identified.
- However, 5-15% of people will have negative (normal) genetic testing of the CCM genes, even though they have multiple CCMs. If a person with multiple CCMs has genetic testing that is inconclusive or negative (normal), this does not rule out a diagnosis of familial CCM.
- Cases with inconclusive results can sometimes be resolved with family studies or as scientific knowledge and testing technology improves over time.
- If a person with multiple CCMs has a negative (normal) genetic test, it may be that their familial CCMs are caused by a mutation that current technologies cannot detect or a different gene or combination of genes.
- People with multiple CCMs and negative genetic testing may be referred to a research study or genetics professional for more in-depth analysis of the three familial CCM genes and/or new genes associated with familial CCM.
Learn more on the webpage, Should I Get Genetic Testing?
Reference:
GeneReviews eBook; Cerebral Cavernous Malformation, Familial http://www.ncbi.nlm.nih.gov/books/NBK1293/
Page last updated 2.18.2026
