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CADASIL.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
2000 Mar 15 [updated 2016 Jul 14].

Author information

1
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
2
Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands

Excerpt

CLINICAL CHARACTERISTICS:

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is characterized by mid-adult onset of recurrent ischemic stroke, cognitive decline progressing to dementia, a history of migraine with aura, mood disturbance, apathy, and diffuse white matter lesions and subcortical infarcts on neuroimaging.

DIAGNOSIS/TESTING:

More than 95% of individuals with CADASIL have pathogenic variants in NOTCH3, the only gene in which mutation is known to cause CADASIL. The pathologic hallmark of CADASIL is electron-dense granules in the media of arterioles, and increased NOTCH3 staining of the arterial wall, which can be evaluated in a skin biopsy.

MANAGEMENT:

Treatment of manifestations: There is no treatment of proven efficacy for CADASIL. Antiplatelet treatment is frequently used, but not proven effective in CADASIL. Migraine should be treated both symptomatically and prophylactically, depending on the frequency of manifestations. Co-occurrence of hypertension, diabetes or hypercholesterolemia should be treated. Supportive care (practical help, emotional support, and counseling) is appropriate for affected individuals and their families. Agents to avoid: Angiography and anticoagulants may provoke cerebrovascular accidents; smoking increases the risk of stroke. Thrombolytic therapy (intravenous thrombolysis) is contraindicated because of the presumed increased risk for cerebral hemorrhage.

GENETIC COUNSELING:

CADASIL is inherited in an autosomal dominant manner. Most affected individuals have an affected parent; de novo pathogenic variants appear to be rare. Each child of an affected person is at a 50% risk of inheriting the pathogenic variant and developing signs of the disease. Prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible if the pathogenic variant in the family is known; however, requests for prenatal testing of typically adult-onset disorders are uncommon.

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