Cerebral cavernous malformation

Title

Other Names:

CCM; Cerebral cavernous hemangioma; Cavernous angioma; CCM; Cerebral cavernous hemangioma; Cavernous angioma; Cavernoma See More

Categories:

Blood Diseases; Congenital and Genetic Diseases; Nervous System Diseases; Blood Diseases; Congenital and Genetic Diseases; Nervous System Diseases; RDCRN See More

Summary Summary

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.^[1]^[2] 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.^[2] Treatment depends upon the symptoms. Seizures are usually treated with antiepileptic medications or surgery.^[1]

Last updated: 12/14/2015

Symptoms Symptoms

Approximately 25 percent of individuals with cerebral cavernous malformations (CCMs) never experience any related medical problems. Other people with this condition may experience serious symptoms including 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.^[2]^[1] Although CCMs have been reported in infants and children, the majority of individuals present with symptoms between the second and fifth decades.^[3]

Last updated: 12/14/2015

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Abnormality of movement	50%
Abnormality of the cerebral vasculature	50%
Arteriovenous malformation	50%
Cavernous hemangioma	50%
Cerebral calcification	50%
Hemiplegia/hemiparesis	50%
Seizures	50%
Abnormality of the retinal vasculature	7.5%
Upper limb phocomelia	7.5%
Visceral angiomatosis	7.5%
Abnormality of the musculature	-
Abnormality of the skin	-
Autosomal dominant inheritance	-
Headache	-
Hepatic vascular malformations	-
Heterogeneous	-
Incomplete penetrance	-
Intracranial hemorrhage	-
Retinal vascular malformation	-

Last updated: 9/1/2016

Cause Cause

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.^[2]

Cerebral cavernous malformations may be familial or sporadic.^[2]^[4] 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.^[2] The underlying cause of sporadic CCMs in unknown and the primary focus of many researchers.^[4]

Last updated: 12/14/2015

Inheritance Inheritance

CCMs occur in about 0.5% of the general population.^[2] There are two forms: familial and sporadic.^[1]^[2]^[4]

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.^[2]^[4] Each child of an individual with familial CCM has a 50% chance of inheriting the mutation.^[3]

Sporadic CCMs occur in people with no family history of the disorder. These individuals tend to have only one CCM.^[2]^[4] Those with sporadic CCM do not have a greater chance of having a child with a CCM than anyone else in the general population.^[4]

Last updated: 12/14/2015

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR 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.

Treatment Treatment

Seizures are usually treated with antiepileptic medications.^[1]^[3] 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.^[1]^[5] Headaches are managed symptomatically and/or prophylactically. Other neurological symptoms may be managed through rehabilitation.^[3]

Last updated: 12/15/2015

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

Prognosis Prognosis

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.^[5] 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.^[1]

Last updated: 12/15/2015

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Cerebral cavernous malformation. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.
The Research Portfolio Online Reporting Tool (RePORT) provides access to reports, data, and analyses of research activities at the National Institutes of Health (NIH), including information on NIH expenditures and the results of NIH-supported research. Although these projects may not conduct studies on humans, you may want to contact the investigators to learn more. To search for studies, enter the disease name in the "Text Search" box. Then click "Submit Query".

Patient Registry

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 registry for patients who wish to be contacted about clinical research opportunities.

For more information on the registry see: http://rarediseasesnetwork.epi.usf.edu/registry/index.htm

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD. Suggest an organization to add.

Organizations Supporting this Disease

Angioma Alliance
502 W. 21st Street, Suite G2-411
Norfolk, VA 23517
Telephone: 757-623-0615
Fax: 757-623-0616
E-mail: info@angioma.org
Website: http://www.angiomaalliance.org

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Cerebral cavernous malformation. This website is maintained by the National Library of Medicine.
The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Cerebral cavernous malformation. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

I was diagnosed with the genetic form of cerebral cavernous malformation (CCM) today and it is believed at least one of my children also has it. Can a person have more than one of the genes that cause this condition? How often does it run in families? See answer
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? See answer

References References

NINDS Cerebral Cavernous Malformation Information Page. National Institute of Neurological Disorders and Stroke (NINDS). February 2015; http://www.ninds.nih.gov/disorders/cavernous_malformation/cavernous_malformation.htm. Accessed 12/14/2015.
Cerebral cavernous malformation. Genetics Home Reference. November 2012; http://ghr.nlm.nih.gov/condition/cerebral-cavernous-malformation. Accessed 12/14/2015.
Morrison L, Akers A. Cerebral Cavernous Malformation, Familial. GeneReviews. May 2011; http://www.ncbi.nlm.nih.gov/books/NBK1293/. Accessed 12/14/2015.
Akers, Amy Ph.D.. Cavernous Malformation. National Organization for Rare Disorders (NORD). 2013; http://rarediseases.org/rare-diseases/cavernous-malformation/. Accessed 12/14/2015.
Altschul D. Intracranial Arteriovenous Malformation: Cavernous Angioma. Medscape Reference. April 2014; http://emedicine.medscape.com/article/252426-overview#a3. Accessed 12/15/2015.