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URL of this page: https://medlineplus.gov/genetics/condition/cerebral-autosomal-dominant-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy/

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Description

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, usually called CADASIL, is a condition that causes neurological problems. The signs and symptoms of CADASIL include:

  • Stroke
  • A decline in memory and intellectual function
  • Changes in mood or behavior
  • Changes in a type of brain tissue called white matter (leukoencephalopathy), which can be seen with magnetic resonance imaging (MRI)
  • Severe headaches (migraines)

CADASIL typically affects adults. However, the specific signs and symptoms, their severity, and the age at which they first appear can vary among affected individuals, even among members of the same family.

In some people with CADASIL, a stroke or stroke-like episode (transient ischemic attack or TIA) is the first sign. People with CADASIL often have multiple strokes or TIAs. These episodes can damage the brain over time, leading to issues such as dementia, changes in mood or behavior, problems with walking, and difficulties controlling the flow of urine (incontinence). Recurrent seizures (epilepsy) may also develop in some people with CADASIL. As the condition progresses, mobility often becomes severely limited, and affected individuals may be dependent on others for their care.

Frequency

CADASIL affects at least 2 to 4 in 100,000 people. Researchers now believe that CADASIL may be more common than previously thought.

Causes

Genetic changes that cause disease are called pathogenic variants. CADASIL is typically caused by pathogenic variants in the NOTCH3 gene. The NOTCH3 gene provides instructions for producing a receptor protein that is important for the normal function of cells called vascular smooth muscle cells, the most common type of cell in most blood vessels. These muscle cells help regulate blood flow by allowing blood vessels to expand and contract. When certain molecules bind to NOTCH3 receptors, the receptors send signals to the nuclei of vascular smooth muscle cells. These signals activate particular genes within these cells.

Pathogenic variants in the NOTCH3 gene can cause cells to produce an altered version of the NOTCH3 receptor. Pieces of these altered receptors form clumps (aggregates) within vascular smooth muscle cells. Through a mechanism that is not well-understood, this leads to the breakdown of vascular smooth muscle cells and a thickening of the blood vessel walls. These changes affect blood flow in the small vessels (arteries) that carry blood from the heart to the brain, particularly the small arteries deep within the brain (cerebral arteries). Reduced blood flow to parts of the brain can cause areas of tissue death (infarcts) that contribute to the signs and symptoms of CADASIL.

Pathogenic variants in at least one gene other than the NOTCH3 gene may cause a rare form of CADASIL.

Learn more about the genes associated with Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Inheritance

As the name implies, CADASIL is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell may be sufficient to cause the disorder. However, the specific signs and symptoms of CADASIL can vary widely among affected individuals. This situation is known as variable expressivity.

In most cases, a person with CADASIL inherits the pathogenic variant from a parent. In rare cases, people with CADASIL have a new (de novo) variant in the gene that occurs during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These individuals typically have no history of the disorder in their family.

Other Names for This Condition

  • CADASIL
  • Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy
  • Familial vascular leukoencephalopathy
  • Hereditary multi-infarct dementia

Additional Information & Resources

Genetic Testing Information

Genetic and Rare Diseases Information Center

Patient Support and Advocacy Resources

Clinical Trials

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

  • Coupland K, Lendahl U, Karlstrom H. Role of NOTCH3 Mutations in the Cerebral Small Vessel Disease Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy. Stroke. 2018 Nov;49(11):2793-2800. doi: 10.1161/STROKEAHA.118.021560. No abstract available. Citation on PubMed
  • Cramer J, Lui F, White ML. Cerebral Autosomal Dominant Arteriopathy. 2024 Mar 21. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK470293/ Citation on PubMed
  • Felix-Ilemhenbhio F, Kocsy K, Azzouz M, Majid A. The role of NOTCH3 in CADASIL pathogenesis: insights into novel therapies. Brain Res. 2025 Sep 15;1863:149754. doi: 10.1016/j.brainres.2025.149754. Epub 2025 May 31. Citation on PubMed
  • Ferrante EA, Cudrici CD, Boehm M. CADASIL: new advances in basic science and clinical perspectives. Curr Opin Hematol. 2019 May;26(3):193-198. doi: 10.1097/MOH.0000000000000497. Citation on PubMed
  • Gatti JR, Zhang X, Korcari E, Lee SJ, Greenstone N, Dean JG, Maripudi S, Wang MM. Redistribution of Mature Smooth Muscle Markers in Brain Arteries in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy. Transl Stroke Res. 2018 Jun 22:10.1007/s12975-018-0643-x. doi: 10.1007/s12975-018-0643-x. Online ahead of print. Citation on PubMed
  • Hack RJ, Rutten J, Lesnik Oberstein SAJ. CADASIL. 2000 Mar 15 [updated 2019 Mar 14]. In: Adam MP, Bick S, Mirzaa GM, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1500/ Citation on PubMed
  • 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. doi: 10.1161/01.res.0000013796.73742.c8. Citation on PubMed or Free article on PubMed Central
  • Hosseini-Alghaderi S, Baron M. Notch3 in Development, Health and Disease. Biomolecules. 2020 Mar 23;10(3):485. doi: 10.3390/biom10030485. Citation on PubMed
  • Joutel A, Corpechot C, Ducros A, Vahedi K, Chabriat H, Mouton P, Alamowitch S, Domenga V, Cecillion 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. doi: 10.1038/383707a0. Citation on PubMed
  • Mizuno T, Mizuta I, Watanabe-Hosomi A, Mukai M, Koizumi T. Clinical and Genetic Aspects of CADASIL. Front Aging Neurosci. 2020 May 7;12:91. doi: 10.3389/fnagi.2020.00091. eCollection 2020. Citation on PubMed
  • 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. doi: 10.1093/brain/awh282. Epub 2004 Sep 13. Citation on PubMed
  • Wang MM. CADASIL. Handb Clin Neurol. 2018;148:733-743. doi: 10.1016/B978-0-444-64076-5.00047-8. Citation on PubMed

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