CADASIL

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.^[1]

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.^[1]

CADASIL is thought to have 100% penetrance.^[2] 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.^[2]

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.^[2]

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.^[2]

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

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.