What is Cadasil (Cerebral Autosomal Dominant Arteriopathy With Sub-Cortical Infarcts And Leukoencephalopathy)

Cerebral Autosomal Dominant Arteriopathy with Sub-Cortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary genetic disorder that causes damage to small blood vessels in the brain, leading to recurrent strokes, cognitive decline, and vascular dementia. It is caused by mutations in the NOTCH3 gene, which progressively restricts blood flow to deep brain structures.

What exactly is CADASIL?

CADASIL is the most common hereditary form of small vessel disease. It specifically affects the smooth muscle cells within the walls of small arteries, causing them to thicken and degenerate. This process limits the brain’s ability to receive oxygenated blood, eventually resulting in white matter lesions and small infarcts (tiny strokes) that accumulate over time.

How does CADASIL affect the body?

Because the condition primarily impacts the brain's microvasculature, the effects are neurological. While every patient's journey is unique, our 57 community members at DiseaseMaps.org frequently report the following clinical features:

• Migraines: Often the first symptom, sometimes accompanied by aura, appearing in early adulthood.


• Recurrent Strokes: Transient ischemic attacks (TIAs) or completed strokes occurring in the absence of traditional cardiovascular risk factors.


• Cognitive Impairment: Progressive challenges with executive function, memory, and attention.


• Mood Disorders: Increased prevalence of depression and apathy.

Who is typically affected by CADASIL?

CADASIL is an autosomal dominant condition, meaning a person only needs to inherit one copy of the mutated NOTCH3 gene to develop the disease. Symptoms usually emerge between the ages of 30 and 50. It affects men and women equally, and because it is genetic, it can be passed from parent to child with a 50% probability. While exact global prevalence is difficult to determine, it is estimated to affect 2 to 5 per 100,000 individuals, though many cases remain undiagnosed.

How is CADASIL different from other strokes?

Unlike common strokes caused by high blood pressure or cholesterol, CADASIL is purely genetic. It is distinct because it occurs in patients who often have no traditional risk factors, such as obesity or smoking. An MRI scan showing specific patterns of white matter hyperintensities in the anterior temporal lobes is a hallmark feature used by clinicians to differentiate CADASIL from other vascular conditions.

Next steps

• Consult a vascular neurologist or a genetic counselor to discuss diagnostic genetic testing.


• Connect with the 57 members of the DiseaseMaps.org community to share experiences and coping strategies.


• Maintain strict control of vascular risk factors like blood pressure to minimize additional strain on damaged vessels.

Medical disclaimer: This information is for educational purposes and should 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


• The CADASIL Foundation: Patient Resources