CADASIL affects roughly 2 to 5 people per 100,000 worldwide, making it rare but not as uncommon as many assume. It is the most common hereditary small vessel disease of the brain, caused by mutations in a single gene passed from parent to child. The true number of people living with CADASIL is almost certainly higher than reported, because the condition is frequently missed or misdiagnosed.
Prevalence by the Numbers
The global estimate of 2 to 5 cases per 100,000 translates to somewhere between 160,000 and 400,000 people worldwide. But prevalence varies dramatically by region. Most provinces of Canada report fewer than 1 case per 100,000. West Scotland sits just under 2 per 100,000. Finland comes in at about 4 per 100,000. The Spanish island of Gran Canaria stands out with roughly 14 cases per 100,000, one of the highest documented rates anywhere.
These figures almost certainly undercount the real burden. When researchers look at the frequency of the gene mutations that cause CADASIL in large genomic databases, they estimate 4.1 to 10.7 carriers per 100,000 people. That is two to five times higher than clinically diagnosed cases, suggesting many people carry the mutation without ever receiving a formal diagnosis.
Why So Many Cases Go Undiagnosed
CADASIL’s symptoms overlap with several more common conditions, which makes it easy to miss. The disease typically shows up between ages 20 and 40, often starting with migraine headaches that include aura. At that age, migraines alone rarely prompt genetic testing. As the disease progresses to strokes and cognitive decline, it can look remarkably similar to multiple sclerosis on brain imaging. Published case reports describe patients who carried a CADASIL diagnosis for years under the label of MS before the correct cause was identified.
The heterogeneity of symptoms adds another layer of difficulty. Some people experience primarily migraines. Others present with strokes in their 40s or 50s. Still others develop mood disorders like depression or apathy as early features. Because no two cases look exactly alike, clinicians who are not specifically thinking about CADASIL may attribute each symptom to a more familiar diagnosis. The disease’s low profile outside of specialty neurology contributes to a cycle: it is considered rare, so it is not tested for, which keeps the reported numbers low.
A Genetic Condition With 50/50 Inheritance
CADASIL follows an autosomal dominant inheritance pattern. If one parent carries the mutation, each child has a 50% chance of inheriting it. You only need one copy of the mutated gene to develop the disease. Unlike some genetic conditions that can skip generations or remain silent, virtually everyone who inherits the CADASIL mutation will eventually show signs of the disease.
The condition is caused by mutations in the NOTCH3 gene, which provides instructions for a protein critical to the health of small blood vessels. Researchers have identified six mutations that account for the majority of cases globally. The most common one has been documented in over 260 patients in clinical studies, yet only 7 carriers of that same mutation appear in the largest public genomic database. That gap reinforces the idea that many carriers have never been clinically evaluated for the condition.
How CADASIL Progresses Over a Lifetime
The disease follows a roughly predictable timeline, though individuals vary. Migraines with aura tend to appear first, often in the 20s or 30s. Strokes come next, with a median age at first stroke of 56 for men and 58 for women. Among patients who experience strokes, about 89% have at least one ischemic stroke (caused by a blocked blood vessel), 28% have at least one transient ischemic attack, and roughly 6% experience a hemorrhagic stroke. Thirty percent of patients who have strokes experience their first one before age 50.
Cognitive decline develops gradually. By age 65, most people with CADASIL have noticeable problems with memory or thinking. The progression eventually affects mobility: men typically need assistance walking by around age 59, women by around 62. Median age at death is 64.6 years for men and 70.7 years for women, a significant gap that holds across studies. Women also tend to experience migraine symptoms more frequently than men, particularly in European populations.
How CADASIL Is Confirmed
Brain MRI is usually the first clue. White matter changes in certain areas of the brain are highly suggestive. Damage visible in the anterior temporal poles (the front part of the temporal lobes, an unusual location for ordinary vascular disease) has about 89% sensitivity and 86% specificity for CADASIL, meaning it catches most true cases while correctly ruling out most non-cases.
Genetic testing for NOTCH3 mutations is the definitive confirmation. In situations where genetic testing is inconclusive, a skin biopsy can be used. The NOTCH3 protein accumulates in small blood vessel walls throughout the body, not just in the brain. Using specialized staining techniques on skin samples, this approach has shown 96% sensitivity and 100% specificity, making it an extremely reliable backup when genetic results are ambiguous.
Rare, but Likely More Common Than We Think
Placing CADASIL in context helps. At 2 to 5 diagnosed cases per 100,000, it falls in the same general range as conditions like Huntington’s disease or amyotrophic lateral sclerosis. But unlike those conditions, CADASIL has no dedicated screening programs and limited awareness outside of academic neurology. The gap between diagnosed prevalence and estimated mutation frequency suggests the real number of affected people could be double or triple what current statistics reflect. As genetic testing becomes more accessible and clinicians grow more familiar with the condition, diagnosed prevalence will likely climb, not because the disease is becoming more common, but because it is finally being recognized.