Cerebral cavernous malformation

While we have not identified any reports of patients with mutations in more than one of the above-mentioned genes, it is not outside the realm of possibility. Nonetheless, it is highly unlikely. Molecular genetic testing can identify if you have one or more of the genes associated with this disorder.

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.

Cerebral cavernous malformations may be familial or sporadic. Familial cases are caused by a mutation in one of at least three particular genes ( KRIT1 , CCM2 , and PDCD10). While the precise functions of these genes are not fully understood, they are believed to interact with each other as part of a complex that strengthens the interactions between cells and limits leakage from the blood vessels. The underlying cause of sporadic CCMs in unknown and the primary focus of many researchers.

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. 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.

You can find a list of laboratories that provide genetic testing for CCM through the Genetic Testing Registry (GTR). The GTR is a centralized online resource for information about genetic tests. The intended audience is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

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.

CCMs occur in about 0.5% of the general population. There are two forms: familial and sporadic.

Familial CCMs, which account for at least 20% of all cases, can be passed from parent to child. Individuals with familial CCMs typically have multiple lesions. Familial CCMs are passed through families in an autosomal dominant manner, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Each child of an individual with familial CCM has a 50% chance of inheriting the mutation.

Sporadic CCMs occur in people with no family history of the disorder. These individuals tend to have only one CCM. Those with sporadic CCM do not have a greater chance of having a child with a CCM than anyone else in the general population.

Cerebral cavernous malformations (CCMs) affect about 0.5 percent of the population worldwide. Eighty percent of these cases are sporadic and 20 percent are familial.

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. Treatment depends upon the symptoms. Seizures are usually treated with antiepileptic medications or surgery.

Some clinicians recommend an MRI examination at regular 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.

To learn more about genetic testing for your family, we recommend that you speak with a genetic professional. Genetics clinics are a source of information for individuals and families regarding genetic conditions, treatment, inheritance, and genetic risks to other family members. More information about finding and visiting a genetics professional is available from the Genetic Consultation Handbook developed by Genetics Home Reference.

To find a genetics clinic, we recommend that you contact your primary healthcare provider for a referral. The following online resources can also help you find a genetics professional in your community:

• GeneTests offers a searchable directory of U.S. and international genetics and prenatal diagnosis clinics.

• The National Society of Genetic Counselors provides a searchable directory of U.S. and international genetic counseling services.

• The American College of Medical Genetics has a searchable database of U.S. genetics clinics.

• The University of Kansas Medical Center provides a list of U.S. and international genetic centers, clinics, and departments.

• The American Society of Human Genetics maintains a database of it members, which includes individuals who live outside of the U. S. Visit the link to obtain a list of the geneticists in your country, some of whom may be researchers that do not provide medical care.

Mutations in at least three genes, KRIT1 (also known as CCM1), CCM2, and PDCD10 (also known as CCM3) are known to cause familial CCM. Mutations in these three genes account for 85 to 95 percent of all cases of familial CCM. The remaining 5 to 15 percent of cases may be due to mutations in unidentified genes or to other unknown causes. Mutations in the KRIT1, CCM2, and PDCD10 genes are not involved in sporadic CCMs. The cause of this form of the condition is unknown.

Some people with CCMs will never know they have the disorder because they will never experience symptoms. Individuals who have increases in size and number of lesions, or an acute brain hemorrhage, may be directed to consider surgical removal. Symptomatic lesions are likely to remain symptomatic or progress. If treated surgically, many of these individuals will experience remission or reduction of symptoms. Overall, the prognosis for CCMs is variable, as the location, size and number of lesions determine the severity of the disorder. In some cases, CCMs can be fatal, in particular if they cause severe brain hemorrhage.

Seizures are usually treated with antiepileptic medications. If seizures don't respond to medication, there is recurring bleeding in the brain, or the lesions are in a surgically accessible location, surgical removal of the lesion(s) using microsurgical techniques may be recommended. Headaches are managed symptomatically and/or prophylactically. Other neurological symptoms may be managed through rehabilitation.

The Brain Vascular Malformation Consortium is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with familial cavernous malformations, Sturge-Weber syndrome, hereditary hemorrhagic telangiectasia through research. The Brain Vascular Malformation Consortium has a list of studies for patients who wish to learn more.

For more information: https://www.rarediseasesnetwork.org/cms/bvmc/Get- Involved/Studies