What is CADASIL?
CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is an inherited disease of the brain's small blood vessels, caused by a mutation in the NOTCH3 gene. Each child of an affected parent has a 50% chance of inheriting it.
One gene, called NOTCH3, carries a fault. The faulty protein builds up in the walls of small arteries in the brain and slowly chokes them. Over years that shows up as migraines, then strokes, then a gradual loss of the mind's ability to plan, focus, and remember. It's inherited in an “autosomal dominant” pattern — one parent has it, and each child has a coin-flip's chance of getting the gene. You can't live your way out of the coin flip, but you have real influence over what happens after it lands.
CADASIL is caused by cysteine-altering mutations in NOTCH3 on chromosome 19. The mutant protein's extracellular domain accumulates as deposits (granular osmiophilic material, “GOM”) around vascular smooth-muscle cells, which degenerate — thickening and narrowing the small arteries and reducing blood flow. Researchers increasingly describe a broader “NOTCH3-spectrum disease,” since some variants cause milder or more variable illness than the classic picture.
Common questions
- Is CADASIL hereditary?
- Yes — autosomal dominant; each child of an affected parent has a 50% chance of inheriting the gene.
- What gene causes CADASIL?
- NOTCH3, on chromosome 19.
- Is CADASIL contagious?
- No. It is genetic, not infectious.
- Can you have CADASIL without a family history?
- Rarely — new (“de novo”) mutations occur but are uncommon.