Short answer · Medically reviewed summary · Last updated: 2026-05-08
Cerebral Autosomal Dominant Arteriopathy with Sub-Cortical Infarcts and Leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene located on chromosome 19. These genetic changes lead to the abnormal accumulation of proteins in the walls of small blood vessels, which gradually damages the vessels and restricts blood flow to the brain. What causes CADASIL? The primary cause of CADASIL is a specific genetic mutation.
Which are the causes of Cadasil (Cerebral Autosomal Dominant Arteriopathy With Sub-Cortical Infarcts And Leukoencephalopathy)?
Causes of Cadasil (Cerebral Autosomal Dominant Arteriopathy With Sub-Cortical Infarcts And Leukoencephalopathy) explained: genetic and environmental factors, reviewed against medical sources, plus patient perspectives.
Cerebral Autosomal Dominant Arteriopathy with Sub-Cortical Infarcts and Leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene located on chromosome 19. These genetic changes lead to the abnormal accumulation of proteins in the walls of small blood vessels, which gradually damages the vessels and restricts blood flow to the brain.
What causes CADASIL?
The primary cause of CADASIL is a specific genetic mutation. Under normal conditions, the NOTCH3 gene provides instructions for producing a protein that maintains the structural integrity of smooth muscle cells in blood vessels. In individuals with CADASIL, these mutations—typically involving a change in the number of cysteine amino acids—cause the protein to misfold and build up, creating toxic deposits known as granular osmiophilic material (GOM) that slowly destroy the vessel walls.
Is CADASIL hereditary?
Yes, CADASIL is an autosomal dominant condition. This means that an individual only needs to inherit one copy of the mutated NOTCH3 gene from one affected parent to develop the disease. Each child of an affected parent has a 50% chance of inheriting the mutation.
Are there other risk factors for CADASIL?
While the genetic mutation is the sole cause, certain factors may exacerbate the symptoms of CADASIL by putting additional stress on already compromised blood vessels:
- Hypertension: High blood pressure significantly increases the risk of stroke.
- Smoking: Nicotine and other toxins can further damage the lining of blood vessels.
- High Cholesterol: Elevated lipid levels can contribute to arterial narrowing.
- Diabetes: Poorly managed blood sugar can accelerate vascular damage.
Is the cause of CADASIL fully understood?
While we understand that NOTCH3 mutations are the root cause, researchers are still investigating exactly how the GOM deposits trigger the specific patterns of white matter disease and cognitive decline seen in CADASIL. Current research focuses on how these protein deposits disrupt cellular communication and whether specific therapies can stabilize the vessel walls to prevent further damage.
Next steps
- Consult a neurologist or a vascular specialist for genetic counseling and diagnostic confirmation via MRI or skin biopsy.
- Manage cardiovascular risk factors (blood pressure and cholesterol) strictly under medical supervision.
- Connect with the 57 members of our CADASIL community at DiseaseMaps.org to share experiences and coping strategies.
Medical disclaimer: This information is for educational purposes only and does not replace professional medical advice, diagnosis, or treatment.
References
- NIH Genetic and Rare Diseases Information Center (GARD): CADASIL.
- Orphanet: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy.
- OMIM (Online Mendelian Inheritance in Man): NOTCH3 Gene Entry.
- CureCADASIL Foundation: Understanding the Genetics of CADASIL.
