CADASIL Syndrome - Essential Facts about this Autosomal Dominant Condition and Stroke Disorder

What is CADASIL Syndrome?

CADASIL Syndrome, also known as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, is one of the most common form of stroke disorders. It is a genetic condition, inherited from one affected parent, which affects smooth muscles of small blood vessels mostly found in the brain. It is classified under the family of leukodystrophies.

In CADASIL Syndrome, there are mutations in the Notch3 gene on the short arm of chromosome 19. Notch3 genes are responsible for stimulating the production of Notch3 receptor proteins. These proteins are needed for the normal functioning of the smooth muscle cells in the blood vessels. Due to these mutations, there is a resulting production and accumulation of abnormal Notch3 receptor proteins causing progressive degeneration in the muscle cells of blood vessels resulting to vascular damage. Over time, this compounded damage results in blood flow limitations causing a transient ischemic attack (TIA) and stroke which are usually the first manifestations of CADASIL syndrome. Other manifestations include psychiatric disorders, confusion, epilepsy, seizures, migraine headaches, dementia and other cognitive impairments.

The common clinical manifestations of this disorder usually appear between 30 and 60 years of age, although the signs and symptoms, age of onset and disease progression usually varies from person to person. Some of the affected individuals have a history of high blood pressure or hypertension, and high cholesterol levels or hypercholesterolemia. However, these common risk factors for stroke are not directly associated with CADASIL Syndrome and their presence does not automatically qualify a person to develop CADASIL Syndrome.

Clinical Manifestations and Diagnosis

Diagnosis for CADASIL syndrome is usually based upon the presenting signs and symptoms of each affected individual. Typical symptoms include stroke-like episodes recurring over a period of time, cognitive disturbances, dementia, migraine and abnormalities in behavior.

CADASIL Syndrome manifestations is often supported by magnetic resonance imaging (MRI) findings, although this is not usually used for diagnosis. The test may reveal white matter hyperintensities, abnormalities in the external capsule, cerebral lacunar lesions and/or cerebral microbleeds. In addition, ultrastructural analysis of small arterioles, which may be obtained through skin biopsy, and Notch3 immunostaining are specific means of confirming the diagnosis. A blood test for the presence of the mutated Notch3 gene is often a helpful screeting test to evaluate the people which may have inherited the condition.

Treatment

There is no specific treatment protocol for CADASIL Syndrome. Treatment is usually focused on the prevention of complications. For example, anti-platelet agents such as aspirin, are given to prevent occurrence of stroke. Medications for hypertension and hypercholesterolemia are also beneficial in patients with CADASIL syndrome. Supportive therapy such as counseling is provided for affected individuals and their families to help them cope with the emotional burden of the disorder.

References

Gene Reviews: CADASIL

The Doctor’s Doctor: CADASIL