General description

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a autosomal dominant hereditary microvascular disease caused by mutations in the NOTCH3 gene on chromosome 19p13.12. NOTCH3 is primarily involved in maintaining vascular wall integrity, and its dysfunction leads to progressive damage to small blood vessels in the brain.

Clinical Features

• Migraine with aura: Typically appears in the third-to-fourth decades of life (20–40 years) and may precede other symptoms.
• Ischemic events: Recurrent transient ischemic attacks (TIAs) and lacunar strokes, often occurring in patients without traditional risk factors like hypertension or diabetes. These strokes usually begin in the 40s or 50s.
• Cognitive impairment and dementia: Progressive cognitive decline and vascular dementia commonly manifest by the sixth decade.
• Additional symptoms: Depression, pseudobulbar palsy, psychosis, focal neurological deficits, and seizures may occur in later stages. By age 60, many patients experience significant functional impairment, including gait disturbances and dependence on care.

CADASIL is relatively rare and affects men and women equally. The onset of symptoms and progression can vary widely, influenced by lifestyle and other genetic factors. While CADASIL does not show a gender difference in prevalence, men may experience earlier functional decline and disability compared to women.