Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, usually called CADASIL, is an inherited condition that causes stroke and other impairments. This condition affects blood flow in small blood vessels, particularly in the brain. An abnormality in the muscle cells surrounding these blood vessels (vascular smooth muscle cells) gradually destroys these cells. The resulting blood vessel damage can cause migraines and other impairments of normal brain function. Later in life, the damaged blood vessels can cause reduced blood flow to various tissues in the body (ischemia). Although the severity of symptoms varies among those affected, people with CADASIL typically have more than one stroke in their lifetime. Recurrent strokes can progressively damage the brain, causing loss of intellectual function (dementia).

CADASIL is not associated with the common risk factors for stroke and heart attack, such as high blood pressure and high cholesterol, although some affected individuals might also have these health problems.

The prevalence of CADASIL is unknown. The estimated prevalence of CADASIL in Scotland is approximately 1 in 50,000 adults; however, this estimate cannot be generalized worldwide.

Mutations in the NOTCH3 gene cause CADASIL. The NOTCH3 gene provides instructions for producing the Notch3 receptor protein, which is important for the normal function and survival of vascular smooth muscle cells. When certain molecules attach (bind) to Notch3 receptors, the receptors send signals to the nucleus of the cell. These signals then turn on (activate) particular genes within vascular smooth muscle cells.

NOTCH3 gene mutations lead to the production of an abnormal Notch3 receptor protein that affects the function and survival of vascular smooth muscle cells. Disruption of Notch3 functioning can lead to the self-destruction (apoptosis) of these cells.

Read more about the NOTCH3 gene.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered NOTCH3 gene in each cell is sufficient to cause the disorder.

In most cases, an affected person inherits the mutation from one affected parent. A few rare cases may result from new mutations in the NOTCH3 gene. These cases occur in people with no history of the disorder in their family.