SNP Shot: Genomic Insights

CADASIL, short for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, is a genetic disorder that leads to strokes and other neurological issues. The primary problem in CADASIL is impaired blood flow within the small blood vessels, especially those in the brain. The vascular smooth muscle cells, which are the muscle cells surrounding these vessels, become dysfunctional and eventually die. This damage to blood vessels (arteriopathy) within the brain can trigger migraines (often with visual disturbances or auras) and/or repeated seizures (epilepsy).

This arteriopathy results in reduced blood flow, which can cause tissue death (infarcts) throughout the body. When an infarct occurs in the brain, it can result in a stroke. Strokes in individuals with CADASIL can occur at any age, from childhood to late adulthood, but most commonly manifest during mid-adulthood. It is common for individuals with CADASIL to experience multiple strokes during their lives. These recurring strokes can progressively damage the brain. Specifically, strokes occurring in the subcortical region, which is crucial for reasoning and memory, can lead to a gradual decline in intellectual abilities (dementia) and changes in mood and personality.

A common finding in individuals with CADASIL is leukoencephalopathy, a change in the brain's white matter that is visible through magnetic resonance imaging (MRI).

The onset and severity of CADASIL symptoms vary significantly among individuals.

Unlike typical stroke risk factors, CADASIL is not linked to high blood pressure or high cholesterol, although some individuals with CADASIL may also have these conditions.

Inheritance:

CADASIL follows an autosomal dominant inheritance pattern. This means that only one copy of the mutated NOTCH3 gene in each cell is enough to cause the disorder. In most instances, an affected individual inherits the mutated gene from one affected parent. Rarely, new mutations in the NOTCH3 gene can cause CADASIL in individuals with no family history of the condition.