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Genetics Home Reference: your guide to understanding genetic conditions
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COL4A1-related brain small-vessel disease

Reviewed September 2011

What is COL4A1-related brain small-vessel disease?

COL4A1-related brain small-vessel disease is part of a group of conditions called the COL4A1-related disorders. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. COL4A1-related brain small-vessel disease is characterized by weakening of the blood vessels in the brain. Stroke is often the first symptom of this condition, typically occurring in mid-adulthood. In affected individuals, stroke is usually caused by bleeding in the brain (hemorrhagic stroke) rather than a lack of blood flow in the brain (ischemic stroke), although either type can occur. Individuals with this condition are at increased risk of having more than one stroke in their lifetime. People with COL4A1-related brain small vessel disease also have leukoencephalopathy, which is a change in a type of brain tissue called white matter that can be seen with magnetic resonance imaging (MRI). Affected individuals may also experience seizures and migraine headaches accompanied by visual sensations known as auras.

Some people with COL4A1-related brain small-vessel disease have an eye abnormality called Axenfeld-Rieger anomaly. Axenfeld-Rieger anomaly involves underdevelopment and eventual tearing of the colored part of the eye (iris) and a pupil that is not in the center of the eye. Other eye problems experienced by people with COL4A1-related brain small-vessel disease include clouding of the lens of the eye (cataract) and the presence of arteries that twist and turn abnormally within the light-sensitive tissue at the back of the eye (arterial retinal tortuosity). Axenfeld-Rieger anomaly and cataract can cause impaired vision. Arterial retinal tortuosity can cause episodes of bleeding within the eye following any minor trauma to the eye, leading to temporary vision loss.

The severity of the condition varies greatly among affected individuals. Some individuals with COL4A1-related brain small-vessel disease do not have any signs or symptoms of the condition.

How common is COL4A1-related brain small-vessel disease?

COL4A1-related brain small-vessel disease is a rare condition, although the exact prevalence is unknown. At least 50 individuals with this condition have been described in the scientific literature.

What genes are related to COL4A1-related brain small-vessel disease?

As the name suggests, mutations in the COL4A1 gene cause COL4A1-related brain small vessel disease. The COL4A1 gene provides instructions for making one component of a protein called type IV collagen. Type IV collagen molecules attach to each other to form complex protein networks. These protein networks are the main components of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. Type IV collagen networks play an important role in the basement membranes in virtually all tissues throughout the body, particularly the basement membranes surrounding the body's blood vessels (vasculature).

The COL4A1 gene mutations that cause COL4A1-related brain small-vessel disease result in the production of a protein that disrupts the structure of type IV collagen. As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes. Basement membranes without these networks are unstable, leading to weakening of the tissues that they surround. In people with COL4A1-related brain small-vessel disease, the vasculature in the brain weakens, which can lead to blood vessel breakage and stroke. Similar blood vessel weakness and breakage occurs in the eyes of some affected individuals.

Related Gene(s)

Changes in this gene are associated with COL4A1-related brain small-vessel disease.

  • COL4A1

How do people inherit COL4A1-related brain small-vessel disease?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. Rarely, new mutations in the gene occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of COL4A1-related brain small-vessel disease?

These resources address the diagnosis or management of COL4A1-related brain small-vessel disease and may include treatment providers.

  • Gene Review: COL4A1-Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK7046)
  • Genetic Testing Registry: Brain small vessel disease with hemorrhage (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1843512)

You might also find information on the diagnosis or management of COL4A1-related brain small-vessel disease in Educational resources (http://ghr.nlm.nih.gov/condition/col4a1-related-brain-small-vessel-disease/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/col4a1-related-brain-small-vessel-disease/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about COL4A1-related brain small-vessel disease?

You may find the following resources about COL4A1-related brain small-vessel disease helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for COL4A1-related brain small-vessel disease?

  • brain small-vessel disease with hemorrhage

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about COL4A1-related brain small-vessel disease?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/gard).

What glossary definitions help with understanding COL4A1-related brain small-vessel disease?

arteries ; autosomal ; autosomal dominant ; basement membranes ; cataract ; cell ; collagen ; gene ; hemorrhage ; hemorrhagic stroke ; imaging ; inherited ; leukoencephalopathy ; magnetic resonance imaging ; migraine ; prevalence ; protein ; pupil ; symptom ; syndrome ; tissue ; tortuosity ; trauma ; white matter

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Lanfranconi S, Markus HS. COL4A1 mutations as a monogenic cause of cerebral small vessel disease: a systematic review. Stroke. 2010 Aug;41(8):e513-8. doi: 10.1161/STROKEAHA.110.581918. Epub 2010 Jun 17. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20558831?dopt=Abstract)
  • Sibon I, Coupry I, Menegon P, Bouchet JP, Gorry P, Burgelin I, Calvas P, Orignac I, Dousset V, Lacombe D, Orgogozo JM, Arveiler B, Goizet C. COL4A1 mutation in Axenfeld-Rieger anomaly with leukoencephalopathy and stroke. Ann Neurol. 2007 Aug;62(2):177-84. (http://www.ncbi.nlm.nih.gov/pubmed/17696175?dopt=Abstract)
  • Vahedi K, Alamowitch S. Clinical spectrum of type IV collagen (COL4A1) mutations: a novel genetic multisystem disease. Curr Opin Neurol. 2011 Feb;24(1):63-8. doi: 10.1097/WCO.0b013e32834232c6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21157337?dopt=Abstract)
  • Volonghi I, Pezzini A, Del Zotto E, Giossi A, Costa P, Ferrari D, Padovani A. Role of COL4A1 in basement-membrane integrity and cerebral small-vessel disease. The COL4A1 stroke syndrome. Curr Med Chem. 2010;17(13):1317-24. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20166936?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: September 2011
Published: February 23, 2015