Rare Infectious Disease News

Disease Profile

Cerebral cavernous malformation

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

CCM; Cerebral cavernous hemangioma; Cavernous angioma;

Categories

Blood Diseases; Congenital and Genetic Diseases; Nervous System Diseases;

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]

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]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Abnormality of the musculature
Muscular abnormality
0003011
Abnormality of the skin
0000951
Autosomal dominant inheritance
0000006
Cerebral calcification
Abnormal deposits of calcium in the brain
0002514
Headache
Headaches
0002315
Hepatic vascular malformations
0006576
Incomplete penetrance
0003829
Intracranial hemorrhage
Bleeding within the skull
0002170
Retinal vascular malformation
0007797
Seizure
0001250

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]

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

    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]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      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

        In-Depth Information

        • 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.
        • 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.

          References

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

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