Finding out the name of the gene variant in the family

This section covers people’s experiences of finding out the genetic variant of MND in the family, including:

  • Routes to finding out
  • Feelings on finding out the name of the gene variant
  • “If it’s going to be any gene, that’s probably the best one to have”: feelings around the genetic variant in the family
  • Not knowing the genetic variant of inherited MND in the family

Some people knew or suspected there was an inherited form of MND in the family before finding out that a gene had been identified.

Routes to finding out

People we interviewed found out the name of the gene variant in the family through various routes. Some people found out through having genetic testing after their own diagnosis. In certain cases, people in this situation might not have a known family history of MND, particularly where neurology clinics offer routine genetic testing to all people with MND.

Others found out through a close relative being tested; people were sometimes told by a family member or were present when a relative with MND was given the results of their genetic test. A few individuals found out through more remote family members getting in touch. After her cousin was diagnosed with MND, Lillian received a letter from the cousin’s partner saying that she’d had genetic testing, which showed she carried the C9orf72 gene variant.

After years of questioning whether there was an inherited form of MND in her family, knowing the name of a gene made it “real”. This was “devastating news” for Lillian, but also a “springboard to make decisions”.

When my cousin knew she’d got motor neurone disease… she wrote to my mum and said, “I’m really sorry to have to tell you I’ve got motor neurone disease.”

At that stage I thought, “This is odd, this is weird”, and it just increased my slight fear about familial motor neurone disease, but at that stage she hasn’t said there’s a gene. And it was when her husband got in contact with me, sent me an email just giving me an update on my cousin after she stopped being able to write and just saying, “she’s now supported…” and whatever “…but they have identified a gene and it’s this one, and there is genetic counselling and whatever available if you’re interested in doing it”.

That was a bit of a bombshell because it changed a worry about something you didn’t know about that wasn’t quantifiable into a really hard quantifiable fact, that there was a gene, that there was a 50/50 likelihood of having inherited it from your parents, or your affected parent. And it just made it very real, it brought it into reality, it gave it a name, it gave it an identity, it gave me something to look on the internet for.

I was thinking there’s something more to this already, so the anxiety was up to about 50%. But when you get the email to say, “This is what it is”, in some ways that was a comfort because actually you’ve got, “You’re right”, everything I’ve been niggling about for many, many years has suddenly come into being, and I knew there was something there. And it is devastating news, but it’s also a springboard to make decisions really, and understand what’s going on and the likelihood of there being better treatment once you’re affected, or even the massive likelihood of gene silencing.

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Some people were told the results of their relative’s genetic test by a healthcare professional. Kelly and Jade were told by their genetic counsellors, who had been given permission by a family member to share this information. Because Sam’s relative died before their genetic test results came back, Sam was given this information directly.

Being told the genetic variant responsible for MND in the family was “more of a bombshell” than Sam expected.

I felt really, really upset. Well, I don’t really get hugely upset, I mean I find it, I found myself really shocked because it wasn’t any new information, apart from the name of the gene. So I was kind of expecting the call and expecting to find out the name of the gene and it would just be stuff I already knew, but I think in the way that it was presented or perhaps just it being very real when you actually know the gene is existing, I found myself very shocked and anxious for about a, well, at least four or five days, I’d say. I mean I was still carrying on my normal life, but it was much more of a bombshell than I had expected.

I suppose before finding out that it was the C9 gene there was a sort of tiny chance that it was just a complete coincidence that two family members had died of the same thing even though I didn’t really believe that coincidence had happened. I suppose knowing the actual gene was upsetting because it’s kind of making it much more real, it’s kind of revisiting the… it’s sort of yeah, it’s kind of in your face I suppose.

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Another person was given the results of her mum’s genetic test after a virtual appointment with her consultant. He asked her to stay behind and told her that her mum’s MND and frontotemporal dementia (FTD) diagnosis was caused by the C9orf72 gene variant. She agreed with him that it would be best to wait to share this information with her dad, who was under a lot of pressure as a primary caregiver. Other people also talked about sharing genetic test results after a diagnosis of inherited MND.

Talking about inherited MND in the family can be difficult, and a few people such as Paul and Adam  described how a gene variant linked to the disease had been identified in a relative, but they weren’t told about it at the time. Adam found out after asking directly and Paul  when a close family member was diagnosed.

Although her cousin had genetic testing which confirmed she had an inherited form of MND, Paul’s mum did not share this with him until after she was diagnosed too.

So, it was very much an unspoken matter because my mum was quite quiet anyway, quite introverted. So, when her cousin suffered and was diagnosed, and I say suffered because by the time my mum wanted to engage with us, her cousin was in a hospice, and had gone through bulbar onset and was towards the end stages, but my mum never wanted to discuss the diagnosis, and she didn’t want to discuss the familial nature of it.

I never really had an opportunity to ask why because when my mum was talking about her diagnosis I was more interested in supporting her than saying, “Why didn’t you engage with us about this earlier?”, and, and about [her cousin’s] sort of position because mum knew at that time that [her cousin] had a familial DNA gene, but she hadn’t really shared that with us until she herself was diagnosed.

So my uncle’s death was unexplained, [her cousin’s] death was explained but to us later. So we were coming to terms, the familial element of the MND was masked by the fact of my mum’s deteriorating condition, looking after her and looking after my dad, it was there in the background but it wasn’t actually something we were really engaging with, and probably didn’t do so until after my mum had passed because that’s a roller coaster both with what you’re planning to do but in timing things before certain aspects of physical deterioration. So, I don’t think if I’m honest that even now four years later we’ve fully grasped the implications.

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When his mum was diagnosed with MND shortly after his aunt died of FTD, Adam joined an online forum to find information about how to support her. Through talking to others, he “pieced things together”, and realised there could be genetic condition in the family. He went to his mum with questions, and she told him that she had previously tested positive for the C9orf72 gene variant. He realised other members of the family including his grandfather and great aunt had also been affected.

Other people we spoke to learnt the name of the gene variant through overhearing conversations. Not everyone could remember how they found out.

Whilst some like Lexi were keen for relatives with MND to have genetic testing, a few people felt that such decisions had been made without giving enough consideration to the possible implications for family members, who then had the knowledge that they could have an increased risk of developing the disease.

Feelings on finding out the name of the gene variant

People described a range of emotions on finding out that a gene variant linked to inherited MND had been identified in the family. Receiving the news that they or other relatives were at an increased genetic risk of developing the disease in the future was a “bombshell” for some. Even where they had suspected it, people described knowing for sure as “shocking”, “upsetting” and “scary”. Whilst Lillian felt knowing the name of the gene made it feel “real”, Jade thought this made it “less scary”.

Finding out the name of the C9orf72 gene variant in her family makes it “less scary”. Jade feels reassured that it is known about and being targeted by research.

When you give something a name, it makes you a bit more confident, doesn’t it? If it doesn’t have a name, it means you don’t know anything about it. But these guys have a name for it, they know what it is, they know how it attacks the cells in the body, and they’re watching it and they’re making real ground-breaking research with it. So it’s reassuring to know it has a name and that we know about it. It’s like we’re not just trying to put our hands out in the dark and find something; we know what this is. That makes it less scary.

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Given their family history, some people weren’t surprised to be told that a gene variant had been identified; they felt this just confirmed what they already knew. Although she “knew what was coming” before she was told, Louisa felt that knowing for sure that her mum carried the C9of72 genetic variant “took the hope away” that it could have been a coincidence. For Dani, finding out about the SOD1 gene variant in the family felt like a “distant thing” at first.

Not everyone realised that there was an inherited form of MND in the family before finding out the results of genetic testing. After Georgia’s mum and aunt were diagnosed with MND, the hospital involved in their care carried out genetic testing. Georgia Z didn’t know much about MND and didn’t realise it was inherited until they got the results. She describes this as “surreal”, “I just couldn’t really believe out of all the families in the world, it was ours”.

Although there could be difficult emotions, some people saw benefits to knowing which gene associated with MND was in the family. Adam said, “You have to be realistic and pragmatic, so I think the hopelessness and the anxiety are definitely there, but there’s also a kind of a proactive instinct that I had to learn about things early, how things would progress, what steps we can take”. Louisa felt a bit conflicted, “I guess it’s better to know so I can try and do something about it… I have absolutely no idea what I can do about it, apart from be involved in research and fundraise as much as I can…. although I’m probably motivated enough to do it anyway”.

The identification of a gene variant linked to inherited MND also meant family members could consider pre-symptomatic genetic testing to find out if they had inherited it. Anthony was glad to have this option after finding out his mum’s condition was caused by the C9orf72 gene variant. Some people, like Harriet were considering genetic testing before or during pregnancy to avoid passing on the gene variant to a future child, though not everyone we talked to felt this was important or necessary. Individuals sometimes felt knowing could help them or their relatives make informed reproductive choices.

Other people knew that their family member had been diagnosed with an inherited form of MND, but they didn’t think too much about the inherited aspect until later on.

When his mum was diagnosed with inherited MND, Richard “boxed it off” and focused on supporting her. After she died, he wrote to her neurologist to ask what gene had been identified.

It was obviously a very raw emotional time, as well, so… but I think I mentioned earlier, it was, it sort of… So the news broke it was, okay, we knew mum had MND, now it transpires its inherited MND. That’s when I sort of boxed it off to revisit it. So, it was undeniably there, and I would start, I did a lot more reading about it and…

So I did that for my self-interest and getting as much knowledge as I could. But at that point in time, it was all about how can we look after my mum. So there was nothing that, it wasn’t as if there was a road I could go down that would sort of help my scenario. That was what it was, and yeah, I’d be lying if it wasn’t on my mind. But it was almost, let’s park that over there. Let’s look after my mum and do what we can with… to help my dad, as well, and then almost let’s revisit that once that’s the only thing that’s on the table.

I think an indicator of how little it was discussed was we had to write to [consultant neurologist] to find out exactly which gene it was, just for our sort of curiosity and how I manage it myself going forward with my family. So, I think that calls out how little it was discussed. It was: “We’ve had the test; it’s genetic; let’s move on with life.”

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Richard points out that knowing he could have an increased chance of developing MND has been a “burden” over time, though he has managed to get to a place where he doesn’t focus on it.

“If it’s going to be any gene, that’s probably the best one to have”: feelings around the genetic variant in the family

C9orf72 was the most common gene variant amongst the people we spoke to, and a few came from a family who had been affected by SOD1. Not everyone could remember the name of the gene in the family, though some people knew they had been told. In other families, a genetic cause of the disease had not been identified, which will be covered below.

The identification of a known genetic variant in the family like C9orf72 or SOD1 could seem a “positive thing” and “almost a relief”. People emphasised ongoing research around inherited forms of MND, which they hoped might mean that they or their family members could benefit from a treatment or cure. John described finding out his condition was caused by the C9orf72 gene variant: “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. In fact, the very first of those which 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”.

For people with MND, it could feel almost like a race for an effective therapy to become available. David had “mixed feelings” on finding out that he had C9orf72-related MND. He said, “My challenge is can I survive long enough to experience the benefits of the research into my genetic mutation?”

Knowing the name of the genetic variant in the family enabled people to look into it further, by researching on the internet or reading scientific papers. Kelly felt that knowing this information “opened up a door for me to understand it”. For Helen, knowing led to new questions.

Helen had never considered that there might be multiple genes which could cause MND. Finding out that her mother-in-law had the C9orf72 genetic variant “opened a whole world of questions”.

(Text edited by Helen)

It sounds so bizarre, but it just didn’t like… It just, whether we’d like just subconsciously put that to the back of our mind to not think about it, I don’t know. I think maybe we just thought there was one gene, one genetic mutation, and his mum had that gene and that’s what it was, and whatever that one gene was is the one that he was at risk of having.

It just never really crossed our minds to look into it at that point in that much depth to even get to the stage of thinking, “Oh, there’s like lots of different genes and…” and when we realised, it was like, “Whoa, we really need to be looking into this” you know. There’s like five main genes out there. Which one is ours? Like there’s a whole world out there. There’s, you know, Facebook forums and groups and research things and trials and we’d been oblivious to all of this. It had sort of passed us by and once, but once we knew that, it was, you know, there was no stopping us then, I think. It was like, it opened a whole world of questions for us and our family that have sort of been answered then the past couple of years.

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Whilst some people were very active in seeking information around inherited MND, other people we talked to didn’t want to know too much.

Not everyone felt it was important or useful to know the name of the gene variant in the family. Maggie didn’t have any hopes for her brother’s genetic test at the time. She said, “It really made no difference, he’s got motor neurone disease, I knew the pathways and the rest of it was just noises in the wind”. For JW, “there was nothing positive at the time”; his focus was on looking after his wife Jean. Not everybody knew much about the different genes associated with inherited MND.

Not knowing the genetic variant of inherited MND in the family

In some families, the genetic variant of inherited MND may not be known, either because genetic testing was not carried out (it may not have been available at the time a relative was diagnosed) or because tests for all the known gene variants came back negative. In cases like this, people may still have to assume that there is an inherited form of MND in the family based on a strong family history.

Some people didn’t think that their relative with MND had had genetic testing. Angi doesn’t remember genetic testing being offered when her mother and sister were diagnosed with MND in a short space of time. As her father also died of MND when she was young, she would like to have known if there was a genetic link. Mary lost her father and grandmother to MND but doesn’t think her father had genetic testing; only the SOD1 gene variant had been discovered at the time of his illness. Although Mary is not sure she would want to have pre-symptomatic genetic testing, part of her wishes a gene had been identified.

However, not everyone wanted to know the genetic variant that could have contributed to the disease in their relatives; William didn’t feel that knowing would be helpful.

William’s dad died of MND when he was a teenager but tested negative for the SOD1 gene variant. After reading a scientific paper some years later, William realised that he could be at risk of developing the disease.

There was a review article in a journal about motor neurone disease written by a specialist in Sheffield. And my mum passed it to me, just kind of in the way that, “Oh, you might find this interesting,” which was just a bit unusual because it wasn’t something we’d really talked about in the family. And in there was comments about inheritance and how much, how little is known, really. And I have to say, at that stage, I remember that being quite upsetting… My understanding was that the gene test had been negative and that we were basically safe as far as we knew, and then I was getting forwarded this article by my mum, saying that actually you’re not safe. Well, not likely. So at that stage I went to genetics locally.
 
So yeah, I went for an appointment there and sort of discussed some issues a little bit, and they weren’t too… I mean, they were well-intentioned but maybe not all that helpful, to be honest. They went back to the hospital my dad had been seen in and asked about the genetic test he’d had, and they were unable to trace anything. And it was unclear to me whether that meant that he hadn’t actually had the test or whether it had just been lost in the records somewhere. And they weren’t really, we didn’t really further explore whether I could be tested at that point. And it’s not something I’ve come back to, and that goes back now sort of 20 years ago, that I was at Genetics. So, things will have changed a lot since then.
 
I’m not sure that would really be very helpful to me. And to be honest, I would probably rather not know. I mean, it wasn’t… I think even if I had a bit of information that could say I’m definitely going to develop such and such at such an age, that would be pretty grim. And then just to add in this sort of uncertainty of it, where you might do or you might not, or it might be something a bit different, you know, that would be even worse, kind of thing. So, I just think its best just to leave it alone at the moment, yeah.

 

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Some people with MND, like Hugh and Stuart, had genetic testing but received a negative or an inconclusive result. Hugh felt “disappointed” that a specific gene had not been identified, as it meant family members could not consider reproductive options, such as genetic testing before or during pregnancy. Stuart felt “relieved” that his results were inconclusive, but his wife Niki found it a difficult position to be in.

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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People’s experiences of receiving a negative result are explored further in the section on genetic testing after a diagnosis of MND.

Finding out about inherited MND in the family

This section covers people’s experiences of finding out about inherited MND (Motor Neurone Disease) in the family, including: Finding out about inherited MND through one’s...