CADASIL Health Article

Diagnosis

CADASIL can be diagnosed via a skin or muscle biopsy. Electron microscope (EM) evaluation of the biopsy specimen will show characteristic abnormalities in smooth muscle cells. These abnormalities are very suggestive of CADASIL, however, the absence of them does not rule out the disorder.

Molecular genetic testing via sequencing of the NOTCH3 gene is also very helpful in the diagnosis of CADASIL. Approximately 95% of affected individuals will have an identifiable mutation in this gene. This testing is offered clinically and can be used to confirm a diagnosis in someone with clinical manifestations or as a predictive test in pre-symptomatic individuals. However, molecular genetic testing is only informative if a mutation can be found in a family. Once a NOTCH3 mutation has been found in an affected individual, family members can be tested for that particular mutation to determine whether or not they have a diagnosis of CADASIL.

Due to the severity of the disease and the lack of effective interventions, special considerations should be given to pre-symptomatic testing for CADASIL. Adequate counseling must be provided, including discussion of motivation for testing, impact of test results, and implications for family members and reproductive decisions. Due to the adult onset of symptoms, it is not recommended that children under the age of 18 are offered testing for CADASIL.

Prenatal diagnosis is possible via molecular genetic testing of the NOTCH3 gene in cells obtained from the fetus, however, this is not a common request due to the adult-onset nature of the disorder.

Treatment and management

Unfortunately, there are no interventions that can effectively prevent CADASIL or its clinical manifestations. Certain signs and symptoms can be treated as they appear (i.e., treating migraine headaches with a drug called acetazolamide). Supportive care can be offered to affected individuals and their families, such as counseling and emotional support.

Prognosis

The prognosis of CADASIL is variable. In a large study, the length of time between onset of symptoms and death ranged from 3–43 years, with a mean of 23 years. The mean age of death in CADASIL patients is about 60 years.

PERIODICALS

Dichgans, Martin. "CADASIL: A Monogenic Condition Causing Stroke and Subcortical Vascular Dementia." Cerebrovascular Diseases 13 Supplement (2002): 37–41.

Dichgans, Martin. "Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy: Phenotypic and Mutational Spectrum." Journal of the Neurological Sciences 203–204 (2002): 77–80.

Kalimo, H., M. Ruchoux, M. Viitanen, and R. N. Kalaria. "CADASIL: A Common Form of Hereditary Arteriopathy Causing Brain Infarcts and Dementia." Brain Pathology 12 (2002): 371–384.

ORGANIZATIONS

National Organization for Rare Disorders (NORD), 55 Kenosia Avenue, PO Box 1968, Danbury, CT 06813-1968. (800) 999-6673. (April 4, 2005.) <http://www.rarediseases.org/search/zcat_search_results?allfields=cadasil& search_for=2>.

WEBSITES

"CADASIL." Genetics Home Reference. (April 4, 2005.) <http://ghr.nlm.nih.gov/condition=cadasil>.

Lesnik Oberstein, S. A. J, M. H. Breuning, and J. Haan. "CADASIL." Gene Reviews. (April 4, 2005.) <http://www.genetests.org/servlet/access?db=geneclinics&site=gt&id=8888891&key=n2v3Fs58ptTtr&gry=&fcn=y&fw=2TuG&filename=/profiles/cadasil/index.html>.

NINDS Multi-infarct Dementia Information Page. National Institute of Neurological Disorders and Stroke. (April 4, 2005.) <http://www.ninds.nih.gov/disorders/multi_infarct_dementia/multi_infarct_dementia.htm>.

Mary E. Freivogel, MS, CGC