Genetic testing after a diagnosis of MND

To date, scientists have identified single gene causes for around 70% of cases of inherited MND, meaning around 7 in 10 people with inherited MND are able to find out the genetic cause of their disease (MND Association 2021). Genetic testing may be offered to people diagnosed with MND, particularly when it is clear that other family members have been affected by MND or FTD (frontotemporal dementia). Genetic testing cannot be used in isolation to make a diagnosis of MND. A diagnosis of MND can only be made based on a person’s symptoms, by an experienced neurologist.

This section covers:

  • Experiences of genetic testing after a diagnosis of MND
  • Being involved in decision-making around genetic testing after a family member’s diagnosis: experiences of other relatives

Read about experiences of finding out the genetic variant of inherited MND in the family.

Experiences of genetic testing after a diagnosis of MND

People we interviewed who had been diagnosed with MND were then offered genetic testing after their diagnosis. People generally had genetic testing through their consultant, though Sarah had genetic testing as part of a research study and was told that the results could affect what studies she was eligible to participate in. The genetic test involves giving a one-off blood sample. David described the process, “it’s just a simple blood test which is taken. I just went from the neurologist along the corridor”.

All of the people we interviewed who were offered genetic testing after their diagnosis decided to go ahead with the test. John felt sure of his decision to have genetic testing, “when I had the diagnosis, there was no question, we needed to know… it matters to know which faulty gene you’ve got, because that could influence future treatments. But given my mother had it, it was almost certain to be hereditary, and so it proved”.

Other people with MND may not want to find out if they carry a gene associated with inherited MND, and family members sometimes have different views.

Sheenagh’s husband, Jim, didn’t want to find out whether he carried a gene variant linked to MND. He gave permission for his blood to be tested but agreed Sheenagh would not tell him the results.

Well, there’s loads, there’s lots of genes. The only one available at that time was called the SOD1 gene, and we did… they asked if my husband if they could take some blood and test it, and he didn’t want to have it done. I don’t know why, because he already had the disease and we already knew he had the disease, but he, he didn’t really want to know any more than he had to know. I, on the other hand, said, “Well, you’ve got three children and if by doing this test further down the line, it could help them, then I think, I think we need to do it.” So he did have the test done; he did not want to know what they found; I did want to know what they found. And that was the way it was left, he didn’t know, I did know. And that’s between me and him [laughs].

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One option people might want to consider is data storage. This is where a person gives permission for their blood sample to be stored, so that their family members can later request genetic testing. Some people might prefer this option if they don’t feel ready to have genetic testing or don’t want to know their results at present. People might also choose to store their blood sample in case it could provide useful knowledge for family members in the future, when scientists have discovered more about inherited MND.

Receiving a positive genetic test enables people to understand the cause of their disease, and also confirms the possibility that other family members may have an increased risk of developing the disease in the future. Family members in this situation may have the option of taking a pre-symptomatic genetic test to find out if they have inherited this genetic variant, which can help inform options when having children. Whilst some people may consider genetic testing before or during pregnancy to prevent passing on the gene variant to future generations, not everyone was comfortable with such options or felt this was necessary due to advances in research and the possibility future children would not be affected. People we spoke to saw having genetic testing after their diagnosis as offering valuable information to their relatives.

After being told about options to prevent inherited MND in future generations, Hugh decided that having genetic testing was a worthwhile thing to do.

If me or any of my offspring or relatives were carrying one of the known gene variants, then you know, in light of the discussions I had with the consultant, then it would be possible to screen embryos of any members of the family choosing to have children thereafter, and then choosing not to go ahead with the pregnancies if the embryos were in fact carrying those gene variations. So, you know, he made it clear that there was a very real chance of wiping out the deleterious gene from the family line, which seemed to be a very worthwhile thing to try and do. Clearly, the starting point had to be whether I was carrying any of those known gene variants, which could then be, other members of the family could then choose to have looked for in their genomes.

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When she was offered genetic testing after her diagnosis, Alison went home to think about it, and discussed it with her children before going ahead. Like Hugh and David, she felt that knowing if she carried a genetic variant could provide important information for future generations. Other people also talked about or shared their decision to have genetic testing with family members.

Genetic counselling can provide information and support to families affected by inherited conditions, and people with MND may be recommended to see a genetic counsellor before having genetic testing. JW and his wife Jean had two sessions before the test, and another discussion afterwards to talk about the results, which JW felt was handled sensitively. Alison had one session with a genetic counsellor, before receiving her results at her next clinic visit. She found genetic counselling valuable, “[it] really laid out the pros and cons, which I suppose when you’re in a state of mental turmoil, it’s difficult to organise your thoughts…. she helped to do that… so that was good. I think essential to have”. Other people we spoke to were not offered genetic counselling or did not feel they needed it.

The people we spoke to received their genetic test results by letter or from their consultant, either over the phone or in person. Stuart’s wife, Niki, found that the results letter used “really quite complex terms”. She looked up the gene variants mentioned on the internet and wrote to the consultant to get some clearer answers.

People with MND described a range of emotions on receiving their genetic testing results. Some of those we interviewed who tested positive for a common genetic variant felt hopeful and positive about developments in research, like John who was told that his condition was caused by the C9orf72 gene variant. He said, “that seemed a little bit of good news because it’s the most common mutation, and there’s a huge amount of research going on into treatments. And in fact, the very first of those with real promise are being trialled around this country right now. So, there is hope, maybe not for me, but for siblings and their children, there’s definite hope”. However, finding out could also be upsetting and difficult.

After being told she carried the C9orf72 gene variant, Sarah felt “guilty”. She said it was disappointing, “but at least there’s proactive things you can do about it”.

It didn’t occur to me it would be inherited until I started reading when I’d been diagnosed, because it, it could have just been unlucky. I could have had a different gene. And when my dad was being tested, he was undergoing research for epidemiology tests, like was it mercury, was it travel, was it the vaccinations he’d had or where he had been in the world? They were looking at all those things that were linking it to be triggered. So my, because I worked in the field with children’s nursing, adult nursing didn’t really… apart from donating money to the MND Association after losing my dad, it didn’t really occur to me that it was going to be inherited at the beginning of the journey. 

I felt guilty and, and sad in a way that I hadn’t been able to stop the process of the gene pathway through the family. But it’s quite good that my children haven’t yet had children and that two of my nephews haven’t had children, so there’s still a chance to knock it on the head from the other members of the family.

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Often, people weren’t surprised to receive a positive result because of their family history. As John said, having the test was “confirmation”. Dani was sure that she carried the SOD1 gene variant which had caused the disease in her siblings, but having this confirmed was “the final nail in the coffin”. JW wasn’t surprised to find out that his wife had the C9orf72 genetic variant, “I’m 99% certain at the time that we knew what the letter would say… It was just another of a long line of disappointments”.

For other people we spoke to, genetic testing failed to identify genetic variant responsible for their condition. Hugh felt disappointed to be told he didn’t carry any of the known genetic variants associated with inherited MND, because it meant family members could not consider reproductive options, such as genetic testing before or during pregnancy. He said, “I hoped it would be one of the known gene variants so yeah, we could set about getting rid of MND in the family”. After she was diagnosed in 2012, Alison was only tested for the C9orf72 gene variant (though it is now common for people with MND to be tested for panels of gene variants).

When she was diagnosed with MND, Alison was only tested for the C9orf72 gene variant. She feels she should be offered further genetic testing, which could provide information for her grandchildren.

The possibilities of further genetic testing, because it would be useful. We’ve got three grandchildren now and we could have that information for them, you know?  At the sort of age when they want it. I must admit, my daughters were… when I told them that I was going to be tested for C9orf, both of them sort of said, “Well, we’ll think about it, we’ll let you know if we want to know what the outcome is,” which I think is, you know, an understandable response. But I think if people have got that information at a younger age, from a step back, from a distance, if you like, I think it would be nice for my grandchildren to know what the situation is.

But nobody thinks to volunteer, I think clinics are under such pressure that nobody thinks to go, “Oh, look, you were only tested for the one genotype, we’ve got…” I don’t know how many we’re up to now, 19 I think when I last looked. Some of them associated with frontotemporal dementia, some of them not. So and certainly my great uncle, his presentation was not with frontotemporal dementia, it was more like an ALS, like me.

We need to know that there’s something useful to be gained by knowing, really. And I think what’s useful for them to be gained, is for their children to know and to be able to take a decision on whether, in the fullness of time, they choose to have children of their own or not. That’s really as far as it goes.

I’m certainly… I look upon it as one of the few constructive things that I could do now, really, for them, is to sort of stamp my foot a bit and say, you know, “Test me for all the known genotypes,” really. I’d rather they had that information. That does mean that obviously, I’m not going to just go and tell five year olds and seven year olds, I would need to discuss it with their parents and that means that their parents would need to be accepting of that information. But I think in the interests of research, it would be useful information as well, you know? I really do.

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Niki’s husband Stuart was relieved when his genetic testing results were inconclusive, but she finds the uncertainty difficult to deal with.

I always thought of it in my own head as a motor neurone disease. So at that point, one began to think, yes. And then because Stuart didn’t want to accept the first diagnosis given to him by his original consultant, when he was told, “I think we need to be considering this as a motor neurone disease,” he didn’t want to accept that, so we went for a second opinion.  And that was extremely helpful, not in terms of reversing what we’d been told, but in terms of confronting us with the fact that we needed to have genetic testing, or he needed to have genetic testing. So it covered the bases that hadn’t been covered before, so that must have been nearly two years into Stuart’s illness. In my own mind from early on, because of the little bit of knowledge of neurology that I have, it had always been motor neurone, so the genetic possibility had been there. For him, not until he was told that genetic testing would be an important thing to have done.

And then, obviously, that was like the world had fallen in because the implications of that are huge. Even though there’s great hope for the future and even though our ability to diagnose and manage even these very severe forms of neurological disorders will get better and better and our understanding will get better and better, you are still thinking, you know, of all the generations to come. Because obviously, you know, your children, your grandchildren and then beyond them, that is your legacy, you don’t want your legacy to be attached to something like potential inherited motor neurone disease. So that, you know, that takes a massive adjustment and was probably the bitterest blow for Stuart that there had been. And so it was a great, it was a great relief for him to get the inconclusive test results back because he could then construe them as being everything’s okay, because the report actually sort of reads in both ways. I find the inconclusiveness very difficult because, you know, you genuinely just don’t know. And since each family member in my husband’s family appears to have had such a different experience of a motor neurone disease, you know, might that be the same for members of our ongoing immediate family, you know, might they be at risk from lots of different variants, if there is such a thing.

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Although Stuart has passed away, Niki plans to keep the conversation on inherited MND and genetic testing open with their children.

Being involved in decision-making around genetic testing after a family member’s diagnosis: experiences of other relatives

Families had different approaches to communicating around genetic testing after a diagnosis of MND. Some people described talking about it within the family before making a decision to go ahead. When his mum was diagnosed with MND, Anthony and his wife were involved in discussions around genetic testing. They wanted her to have the genetic test, which his mum was happy to do. Sam had been keen for their relative to have the test and said, “I was very keen for them to have the genetic test because then it opened up our options a lot… we already knew almost for sure that we had a genetic inherited risk, so knowing which gene it was…. seemed like a logical thing to do for me”. Lexi thinks her mum had genetic testing alongside other investigations when she was diagnosed. She can’t remember whether her mum had the option of not having the test, but thinks it is important to understand.

Louisa and Richard were both aware that their parents were going to have genetic testing after their diagnoses but feel that more time should have been taken to discuss the implications. Richard wasn’t involved in conversations around genetic testing when his mum was diagnosed. He questions whether this should have been discussed with the wider family, as he now has the “burden” of knowing that he could have inherited the C9orf72 gene variant. As Louisa says, “It’s just a blood test result but it’s not really just a blood test result, do you know what I mean?”

In hindsight, Louisa feels that the decision for her mum to have genetic testing after her diagnosis was made too quickly. The test results are “a big nugget of information that I don’t know what to do with”.

That was quite quick actually, and in hindsight it was probably too quick. It was a case of, “We can do your blood tests and one of them can include looking at your genes, what you might have, given that your mum, your gran” – my grandma – “Your mum had it”. And the doctor asked a lot about anyone else, like her parents that had had a diagnosis of dementia or motor neurone disease. It probably lasted about a minute or two, I mean to give him the benefit of the doubt it maybe went up to five, with going back into the family history and stuff …. And then it was just like, “Yeah, well I guess so”.
 
Then the next thing… I maybe helped my mum say yes to that, I don’t know, I couldn’t be 100% sure to be honest. I feel like it just happened quickly, it was a blood test that she could have done and then it wasn’t really a lot about the impact of the information discussed at the point of testing, “Shall we test? This might bring up this problem and this problem and this problem”. Maybe there was a little, wasn’t enough of that or a lot of that.
 
I guess I feel like finding out its inherited is huge. There was so much gravity on the first neurologist not diagnosing my mum with motor neurone disease and waiting for a specialist to do that because of the gravity of the diagnosis, that I feel like that was pitched right. Yet, the inherited factor doesn’t have the same pitch. The gravity is the same for me – I mean it’s not the same, you’re not actually being told you’re going to get it – but the feeling that you get is like that.
 
So probably yeah, it needs to be… I know it’s held in high regard, I know that it’s not taken lightly that people give this information and I think that mum’s neurologist is amazing, his way of speaking with us and her is brilliant. I guess it’s just, what I’ve found is it’s just a big nugget of information that I’ve got now that I don’t know what to do with. So, something that would be like helpful about that would help.
 
Yeah. Are you thinking of anything specific?…
 
I’m not really thinking of anything in particular, I just feel more time dedicated to that information given. It’s just a blood test result but it’s not really just a blood test result, do you know what I mean? I don’t know, maybe your own appointment, separate appointment, because then I could speak about all my irrational thoughts and feelings, or rational, maybe one or the other, without being in front of mum and dad. There’s questions that I might’ve asked at the point of testing for genetics, doing the test, if my mum and dad hadn’t had been there.

 

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