GENETIC TESTING
Genetic testing takes two forms: diagnostic and predictive. In both cases, testing of a gene known as NOTCH3 is undertaken. Changes in the NOTCH3 gene are known to be associated with the development of CADASIL.
For this reason, if we can detect an abnormality on genetic testing, we can be 100% sure that someone has CADASIL. In CADASIL the abnormalities that occur are all within one gene which is called NOTCH3. However, this gene is made up of many thousands of building blocks (base pairs). In CADASIL, there is an abnormality (mutation) in only one of these. Testing for this can be a very time-consuming process. For this reason routine genetic testing of the whole gene is not always performed in CADASIL. Most of the abnormalities tend to occur in certain parts of the gene and many laboratories only screen these parts of the gene. We have carried out studies to show that limited screening can pick up about 90% of NOTCH3 gene changes in a UK population. However, increasingly with new technology laboratories are screening the whole gene to look for abnormalities.
DIAGNOSTIC GENETIC TESTING
This form of testing is undertaken where there is a strong clinical suspicion that an individual has CADASIL. This means that if you are having symptoms of CADASIL or you have had an MRI scan of the brain or a skin biopsy and the findings suggest a diagnosis of CADASIL then a genetic test can be used to confirm the diagnosis. If a change is found within the NOTCH3 gene then this makes the diagnosis 100% certain. In individuals showing characteristic signs of the disease on the MRI scan, and having symptoms such as migraine, the chance of finding a NOTCH3 gene change is about 90%.
Genetic testing for CADASIL requires only a blood sample or in some cases a sample of spit can be used. Testing in the laboratory takes approximately six to eight weeks. The individual being tested would normally be seen in the clinic to receive the results of the test. This allows discussion about the diagnosis and future management. Once a gene change has been found in an affected individual, predictive testing of other, unaffected, relatives is possible.
PREDICTIVE GENETIC TESTING
This form of genetic testing is undertaken on individuals who have no obvious signs of CADASIL but have an affected relative (usually a first degree relative – i.e. parent, sibling or child). Each individual with a first degree relative affected by CADASIL has a 1 in 2 chance of having the same gene change. An individual who inherits a gene change will almost certainly, at some stage in their life, develop some signs and symptoms of the disease. It is not possible by doing the genetic test to determine whether an individual would be affected at all, or the age at which they may be affected. We could not say whether the individual would be affected by strokes, migraines or depression, or any combination of the three symptoms. An individual without the gene change is very unlikely to develop CADASIL.
Whether or not to have a predictive genetic test is a difficult but important decision for each individual who is suspected of being at-risk of CADASIL. Our usual protocol for undertaking predictive testing involves at least two visits to the clinic prior to undertaking the test. This allows us to give you all the information that you need and gives you time to go away and think about the implications of your decision and how you might deal with the result. You will also have the opportunity to discuss this with your friends and family.
ISSUES TO CONSIDER WHEN UNDERTAKING GENETIC TESTING
There are numerous psychological and emotional consequences of genetic testing and it may be helpful to consider these before one goes through the procedure. It is important to bear in mind that if you have a predictive genetic test for CADASIL and you are found to be a carrier, that does not mean that you have CADASIL but you will have an increased risk of developing the condition in the future. The results from genetic testing could provide reassurance and relief from uncertainty, particularly in cases where not knowing presents its own challenges. However, it is possible that if one is found to be a carrier of the disease, this could lead to worries about what the future may be like. This can sometimes lead to feelings of depression or anxiety. Feelings of guilt have also been reported in the research literature in cases where people are found not to be carriers of the disease. This is often in the context where one or more siblings have been found to be carriers of the disease while others are spared. The genetic nature of CADASIL means that it is not possible to control who will and won’t inherit the disease. Following a test it is common for there to be a period of adjustment as you come to terms with the result and what it means for you.
Our experience has shown that the process of genetic testing itself is associated with feelings of anxiety among individuals and their families. The anxiety is often triggered by anticipation of waiting for the results. It is often helpful if an individual arrives for testing with a close friend or relative to accompany and support them.
INSURANCE IMPLICATIONS
Predictive genetic tests for CADASIL
Some people ask about the implications for insurance premiums of undertaking a predictive genetic test and possibly finding that you are at a high risk of developing the condition in the future. Currently in the UK there are limited implications as there is an agreement between the Association of British Insurers and the UK Government called “The Code on Genetic Testing and Insurance”. This code aims to provide reassurance about how genetic testing could affect insurance. This code covers most insurance business in the UK and states that insurance companies should not require or pressure you to have a genetic test or ask for the results of a predictive genetic test when determining the premium for an insurance policy.
If you are already paying a higher premium due to your family history of CADASIL but then you have a predictive genetic test which shows you do not carry the gene change, you may choose to inform the insurance company about your result. Some insurance companies will reduce your premium based on a predictive genetic test result that shows you are not at risk. You should visit the company’s website or contact them to find out whether and how they take ‘negative’ predictive genetic test results into account when determining your insurance terms.
Diagnostic genetic tests for CADASIL
Please bear in mind that when you do fill in an application form for an insurance policy that you should answer all the questions to the best of your ability and honestly. If questions are not answered honestly, particularly those regarding the family history, it could invalidate your own insurance. The code also states that a diagnostic genetic test is treated the same as other diagnostic medical tests like blood tests or examinations and, therefore, this information may need to be declared if relevant.
It is important to remember that if you have a predictive genetic test for CADASIL and you are found to be a carrier of the gene change this does not mean that you have a clinical diagnosis CADASIL, but you will have an increased risk of developing the condition in the future. CADASIL can only be diagnosed clinically with an MRI scan or by neurological examination.
Download the Association of British Insurer's Code on Genetic Testing and Insurance.