CADASIL

What causes CADASIL?

CADASIL is caused by a variant (mutation) in the NOTCH3 gene. The NOTCH3 gene gives the body instructions to make the Notch3 receptor protein, needed for normal function and survival of vascular smooth muscle cells. Mutations in NOTCH3 cause the body to make an abnormal protein, thus impairing the function and survival of vascular smooth muscle cells and causing these cells to self-destruct. The loss of vascular smooth muscle cells in the brain causes blood vessel damage that leads to the characteristic features of CADASIL.

Last updated on 05-01-20

Can CADASIL cause lesions in the brain?

Yes. CADASIL can cause changes (lesions) in the brain. CADASIL affects the arteries in the brain, causing them to narrow or break down. This affects the flow of blood to the brain, reducing the amount of oxygen which is delivered, which can damage brain tissue over time. Damaged tissue could appear as a lesion on a magnetic resonance imaging (MRI) test.

Last updated on 05-01-20

How is CADASIL inherited?

CADASIL is inherited in an autosomal dominant manner. This means that having a mutation in only one copy of the responsible gene in each cell is enough to cause CADASIL. In most cases, an affected person inherits the mutated gene from an affected parent. In rare cases, CADASIL may result from having a new mutation in the gene, in which case it is not inherited from a parent.

When a person with an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit the mutated copy of the gene.

Last updated on 05-01-20

If a parent has CADASIL, are his or her children at risk to inherit the condition?

Every child of an individual with one NOTCH3 mutation has a 50% (1 in 2) chance of inheriting the mutation.

Last updated on 05-01-20

Can CADASIL skip a generation?

CADASIL is thought to have 100% penetrance. This means that all people who inherit the mutated gene responsible for CADASIL will be affected. However, the age of onset, severity of symptoms, and progression of the disease varies. Likewise, those who do not inherit the mutated gene will not be affected.

Most people diagnosed with CADASIL have an affected parent. However, the family history may appear to be negative because of failure to recognize symptoms in family members, early death of an affected parent before the onset of symptoms, or late onset of the disease in the affected parent.

If molecular genetic testing has identified the specific mutation present in the NOTCH3 gene in an affected family member, testing of at-risk, asymptomatic adult relatives is possible.

  • If the son or daughter of an affected person with an identified mutation is tested and is not found to have the mutation, they will be unaffected and also are not at risk to pass the mutation on to their children or (grandchildren). This means that CADASIL cannot skip a generation; the mutation would not "reappear" in a future generation once it has not been passed down.
  • If a family member does have the mutation and is asymptomatic, while they will become affected at some point, genetic testing is not useful in predicting age of onset, severity, type of symptoms, or rate of progression.

In a family with an established diagnosis of CADASIL, testing is appropriate to consider in symptomatic people regardless of age. However, testing of asymptomatic people who are younger than 18 years who are at risk for adult- onset disorders for which no treatment exists is not considered appropriate.

Genetic counseling is strongly recommended for people considering genetic testing for a family history of CADASIL.

Last updated on 05-01-20

Is it possible to have multiple sclerosis and CADASIL?

Theoretically, it is possible for an individual to develop both multiple sclerosis and CADASIL. However, because both conditions are uncommon, it would be extremely unlikely to have both. It is more likely that an individual has only one of these conditions. The two conditions can cause similar symptoms, such as changes in brain tissue (lesions) shown on magnetic resonance imaging (MRI), which can complicate the process of arriving at the correct diagnosis.

Articles in the medical literature mention that MS is the most common misdiagnosis for individuals with CADASIL. Several tests may help to clarify which diagnosis is correct: the finding of a NOTCH3 mutation on genetic testing is considered diagnostic of CADASIL; the finding of certain proteins in cerebral spinal fluid from a spinal tab may help establish a diagnosis of MS.

Last updated on 05-01-20

What is the long-term outlook for people with CADASIL?

Symptoms of CADASIL usually progress slowly. By age 65, most people have severe cognitive problems and dementia. Some people lose the ability to walk, and most become completely dependent on the care of others due to multiple strokes. Life expectancy in people with CADASIL is reduced, mainly because of lung or heart problems.

Last updated on 05-01-20

How might CADASIL be treated?

There is no cure or effective treatment for CADASIL yet. While antiplatelet treatment is often used, it is also not proven to be useful and some professionals do not recommend using these because microbleeds in the brain may occur in people with CADASIL, and, for this reason, the safety of antiplatelet drugs in this disease is still unknown.

Migraine should be treated both symptomatically and prophylactically (with preventative methods), depending on the frequency of symptoms. Some medication that have shown some efficacy in some studies, but have not being proven may include acetazolamide, and sodium valproate for the migraine, and acetylcholinesterase inhibitor for cognitive decline.

When hypertension, diabetes or hypercholesterolemia (high cholesterol) are also present, they should be treated. Supportive care, including practical help, emotional support, and counseling, is useful for affected people and their families.

Yearly follow up by a neurologist with expertise in CADASIL is recommended from the time of diagnosis, as well as other specialists as needed.

Smoking, angiography, anticoagulants and thrombolytic therapy are all to be avoided by those with CADASIL as they increase the risk of strokes and/or brain bleeding.

Last updated on 05-01-20

Name: United Leukodystrophy Foundation (ULF) 224 North Second Street Suite 2
DeKalb, IL, 60115 , United States
Phone: 815-748-3211 Toll Free: 800-728-5483 Fax : 815-748-0844 Email: office@ulf.org Url: http://www.ulf.org/
Name: CADASIL-Together We Have Hope 3605 Monument Drive
Round Rock, TX, 78681-3707,
Phone: 512-255-0209 Toll Free: 877-519-HOPE Email: info@cadasilfoundation.org Url: http://cadasilfoundation.org/
Name: Alex The Leukodystrophy Charity Alex TLC 45 Peckham High Street
London, SE15 5EB, United Kingdom
Phone: 020 7701 4388 Email: info@alextlc.org Url: https://www.alextlc.org
Name: cure CADASIL Association 10 Schalks Crossing Road Suite 501A-133
Plainsboro, NJ, 08536, United States
Phone: 307-215-9840 Email: info@cureCADASIL.org Url: http://www.cureCADASIL.org

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The RareGuru disease database is regularly updated using data generously provided by GARD, the United States Genetic and Rare Disease Information Center.

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