“To test or not to test”, that is the question

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A huge ‘atlas’ mapping the locations of motor neurone disease (MND) causing mutations within the genetic code has been collated. This has followed years of genetic analysis and sequencing of the DNA of people with MND, and their family members.

The people who have given their time and DNA have played a hugely important part in helping researchers learn more about MND, particularly the inherited form of the disease. Dr Benatar, who spoke in this session highlighted “there is a desire and interest by people who may have inherited MND to contribute to research into this disease, if not for their benefit then for the benefit to future generations of their family“.

The first session on day two of the Symposium looked at the topic of genetic testing and counselling. All the presentations had a common theme of this topic being a two-way street – after all the help people with MND and their families have given to help with research, now research efforts have been focussing on the ways to better help those who decide to have genetic testing for inherited/familial MND.

Inherited MND

The inherited form accounts for about 5-10% of all cases of MND. We can now pinpoint the genetic cause for about 60-70% of people who have inherited MND. Only once you know the genetic mutation causing of a person’s MND can you test to see if that mutation is present in other family members.

Tests are available for the most common gene mutations: SOD-1, TDP-43, C9orf72 and FUS. Some of the rarer mutations that cause MND do not have tests, and there are still gene mutations to identify (those that cause the other 30-40%). Prof Chris Shaw (King’s College London) who presented in this session remarked that testing is tricky if you do not know which gene is responsible, and that ‘the changes of finding a mutation is approximately 5% if you do not know what you are looking for’.

More information about the genetics of MND is on our website.

Offering those at risk of developing MND pre-symptomatic genetic testing

Families with a history of MND can undergo testing for MND-linked genes before any symptoms of the disease appear. This is known as pre-symptomatic genetic testing.

The Pre-Symptomatic Familial ALS (Pre-fALS) study in the USA looks at people who are at genetic risk for MND. It is now in its eighth year. Dr Mike Benatar from the University of Miami presented on this study on day two of the Symposium.

People taking part in this study are at a higher risk of developing MND because they have two blood relatives with MND or FTD, (a sign that it is more likely the inherited form of MND is present in their family tree).

People taking part in the study can take a test for the MND-causing gene mutation known to be present in their family. Those who have been tested can chose whether they want to know the results, though in the Pre-fALS study Dr Benatar said about 80% of people wanted to know their results.

Over the course of the study, the researchers’ approach has changed with regard to the use of genetic counselling. Some of their focus has been on communicating the limitations of current genetic testing and knowledge, and the directions that can be taken once a positive or negative test result is known.

How can pre-symptomatic testing help researchers?

The pre-symptomatic phase is the key to learning more about MND. Monitoring someone through this phase of the disease could help to pinpoint the onset of MND.

The early stages of the disease are the hardest to study, due to how long it takes to diagnose MND from when the first symptoms present. Knowing more about the early stages of the disease could give researchers the best chance of finding therapies and treating this disease early on.

What does this actually mean for people with a family history of inherited MND?

A positive test result – having the mutation present – may not even mean you will 100% go on to develop MND.

Ultimately, knowing whether you carry a MND causing mutation does not change the progress of the disease. It is hard to say that far down the line what treatments will be available or if there would be a cure then.

Find out that you could get MND in a few decades time could mean linking every muscle cramp or twitch to the first signs of MND.

What does this all mean for those family members of someone with sporadic MND?

Prof Chris Shaw make a good point that it is tricky to know what is sporadic MND and what is inherited MND – the distinction is becoming increasingly blurred, and it made more difficult when there is little or incomplete knowledge of the family history.

Genetic testing and counselling: the future

For genetic testing going forward, a few parts of the process need improvement, such as:

  • Working out when testing is appropriate
  • Interpretation of test results – genetic testing may pick up gene variants (which we all have, it makes us unique), but the difficulty is getting biological proof that this variant is related to MND
  • Providing follow up counselling after taking the test and getting the result.

More information:

We produce a series of information sheets on inherited MND. Part 1 is an overview of inherited MND, part 2 goes into more detail about genetic counselling and genetic testing, and part 3 covers options when starting a family, including pre-implantation genetic diagnosis.

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