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Genetics Home Reference: your guide to understanding genetic conditions
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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

(also known as CADASIL)
Reviewed May 2008

What is CADASIL?

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, usually called CADASIL, is an inherited condition that causes stroke and other impairments. This condition affects blood flow in small blood vessels, particularly in the brain. An abnormality in the muscle cells surrounding these blood vessels (vascular smooth muscle cells) gradually destroys these cells. The resulting blood vessel damage can cause migraines and other impairments of normal brain function. Later in life, the damaged blood vessels can cause reduced blood flow to various tissues in the body (ischemia). Although the severity of symptoms varies among those affected, people with CADASIL typically have more than one stroke in their lifetime. Recurrent strokes can progressively damage the brain, causing loss of intellectual function (dementia).

CADASIL is not associated with the common risk factors for stroke and heart attack, such as high blood pressure and high cholesterol, although some affected individuals might also have these health problems.

How common is CADASIL?

The prevalence of CADASIL is unknown. The estimated prevalence of CADASIL in Scotland is approximately 1 in 50,000 adults; however, this estimate cannot be generalized worldwide.

What genes are related to CADASIL?

Mutations in the NOTCH3 gene cause CADASIL. The NOTCH3 gene provides instructions for producing the Notch3 receptor protein, which is important for the normal function and survival of vascular smooth muscle cells. When certain molecules attach (bind) to Notch3 receptors, the receptors send signals to the nucleus of the cell. These signals then turn on (activate) particular genes within vascular smooth muscle cells.

NOTCH3 gene mutations lead to the production of an abnormal Notch3 receptor protein that affects the function and survival of vascular smooth muscle cells. Disruption of Notch3 functioning can lead to the self-destruction (apoptosis) of these cells.

How do people inherit CADASIL?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered NOTCH3 gene in each cell is sufficient to cause the disorder.

In most cases, an affected person inherits the mutation from one affected parent. A few rare cases may result from new mutations in the NOTCH3 gene. These cases occur in people with no history of the disorder in their family.

Where can I find information about treatment for CADASIL?

You may find information on treatment or management of CADASIL or some of its symptoms in the links below, particularly the links for Gene Reviews, MedlinePlus Encyclopedia, Educational resources, and Patient support.

Where can I find additional information about CADASIL?

You may find the following resources about CADASIL helpful. These materials are written for the general public.

  • MedlinePlus - Health information
    • Encyclopedia: Multi-infarct dementia (http://www.nlm.nih.gov/medlineplus/ency/article/000746.htm)
    • Health Topic: Dementia (http://www.nlm.nih.gov/medlineplus/dementia.html)
    • Health Topic: Stroke (http://www.nlm.nih.gov/medlineplus/stroke.html)
  • Additional NIH Resources - National Institutes of Health
    • National Institute of Neurological Disorders and Stroke: CADASIL Information Page (http://www.ninds.nih.gov/disorders/cadasil/CADASIL.htm)
    • National Institute of Neurological Disorders and Stroke: Stroke: Hope Through Research (http://www.ninds.nih.gov/disorders/stroke/detail_stroke.htm)
  • Educational resources - Information pages
    • Ask the Geneticist: Inheritance of CADASIL (http://www.genetics.emory.edu/ask/question.php?question_id=3919)
    • Ask the Geneticist: Onset of symptoms of CADASIL (http://www.genetics.emory.edu/ask/question.php?question_id=722)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=136)
  • Patient support - For patients and families
    • American Stroke Association (http://www.strokeassociation.org/presenter.jhtml?identifier=1200037)
    • Genetic Alliance (http://www.geneticalliance.org/ws_display.asp?filter=infosearch_results&info_keyword=CADASIL&expand=Treatment)
    • United Leukodystrophy Foundation, Inc. (http://www.ulf.org)

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

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=cadasil)
  • Gene Tests - DNA tests ordered by healthcare professionals (http://www.genetests.org/query?testid=26337)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/search/condition=%22cadasil%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((Dementia,+Multi-Infarct[MAJR])+OR+(CADASIL[MAJR]))+AND+(CADASIL[TIAB])+AND+english[la]+AND+human[mh]+AND+"last+720+days"[dp])
  • OMIM - Genetic disorder catalog (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=125310)

What other names do people use for CADASIL?

  • Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy
  • Familial vascular leukoencephalopathy
  • Lacunar Dementias
  • Multi-Infarct Dementia

See 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 CADASIL?

  • See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
  • Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
  • Submit your question to Ask the Geneticist (http://www.askthegen.org/).

What glossary definitions help with understanding CADASIL?

apoptosis ; arteriopathy ; autosomal ; autosomal dominant ; cell ; cholesterol ; dementia ; familial ; gene ; heart attack ; infarct ; ischemia ; leukoencephalopathy ; migraine ; molecule ; mutation ; new mutation ; nucleus ; prevalence ; protein ; receptor ; risk factors ; subcortical ; symptom ; tissue ; vascular

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

References
  • Buffon F, Porcher R, Hernandez K, Kurtz A, Pointeau S, Vahedi K, Bousser MG, Chabriat H. Cognitive profile in CADASIL. J Neurol Neurosurg Psychiatry. 2006 Feb;77(2):175-80. (http://www.ncbi.nlm.nih.gov/pubmed/16421118?dopt=Abstract)
  • Dichgans M. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: phenotypic and mutational spectrum. J Neurol Sci. 2002 Nov 15;203-204:77-80. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12417361?dopt=Abstract)
  • Haritunians T, Boulter J, Hicks C, Buhrman J, DiSibio G, Shawber C, Weinmaster G, Nofziger D, Schanen C. CADASIL Notch3 mutant proteins localize to the cell surface and bind ligand. Circ Res. 2002 Mar 22;90(5):506-8. (http://www.ncbi.nlm.nih.gov/pubmed/11909813?dopt=Abstract)
  • Joutel A, Corpechot C, Ducros A, Vahedi K, Chabriat H, Mouton P, Alamowitch S, Domenga V, Cécillion M, Marechal E, Maciazek J, Vayssiere C, Cruaud C, Cabanis EA, Ruchoux MM, Weissenbach J, Bach JF, Bousser MG, Tournier-Lasserve E. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature. 1996 Oct 24;383(6602):707-10. (http://www.ncbi.nlm.nih.gov/pubmed/8878478?dopt=Abstract)
  • Kalaria RN, Viitanen M, Kalimo H, Dichgans M, Tabira T; CADASIL Group of Vas-Cog. The pathogenesis of CADASIL: an update. J Neurol Sci. 2004 Nov 15;226(1-2):35-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15537516?dopt=Abstract)
  • Louvi A, Arboleda-Velasquez JF, Artavanis-Tsakonas S. CADASIL: a critical look at a Notch disease. Dev Neurosci. 2006;28(1-2):5-12. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16508299?dopt=Abstract)
  • Opherk C, Peters N, Herzog J, Luedtke R, Dichgans M. Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients. Brain. 2004 Nov;127(Pt 11):2533-9. Epub 2004 Sep 13. (http://www.ncbi.nlm.nih.gov/pubmed/15364702?dopt=Abstract)
  • Rufa A, Guideri F, Acampa M, Cevenini G, Bianchi S, De Stefano N, Stromillo ML, Federico A, Dotti MT. Cardiac autonomic nervous system and risk of arrhythmias in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Stroke. 2007 Feb;38(2):276-80. Epub 2007 Jan 11. (http://www.ncbi.nlm.nih.gov/pubmed/17218610?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: May 2008
Published: November 20, 2009