What is the role of genetic testing in the diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)?

Updated: Oct 09, 2018
  • Author: Reza Behrouz, DO, FACP; Chief Editor: Helmi L Lutsep, MD  more...
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Genetic testing is commercially available to detect mutations in NOTCH3. A small amount of venous blood is needed for the test (10 mL of whole blood in Lavender top tube, refrigerated). More than 90% of patients with CADASIL have mutations (mostly missense) in the NOTCH3 gene. [18] Also, approximately 90% of mutations could be detected within a few exons (exons 2-6). [19] Thus, genetic testing should initially be focused on these exons. Currently available genetic testing has a sensitivity approaching 100%.

Genetic testing for CADASIL is indicated when clinical findings (migraines with early-onset strokes and dementia) and radiographic (MRI) findings raise a high index of suspicion. Diffuse white matter disease in a young patient who suffers from migraines and who has a family history of early stroke raises the suspicion of CADASIL. Genetic testing for asymptomatic family members of CADASIL patients is available. However, the affected family member must be tested first to assess the sensitivity of the test.

A newly developed screening tool, the CADASIL scale, was designed to select patients with a high probability of being affected who should undergo genetic testing. While the scale needs validation, it is a good first step and highlights the prominent features of the disease. [20]

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