Lisa Beaton, Dr Celine Lewis, Jana Gurasashvili and Louise Fish: Hope for those with "no primary findings"

There are a range of outcomes from a genomic test. The results
might provide a diagnosis, there may be a variant of uncertain
significance, where a genetic variant is likely the cause of the
condition, or there might be no particular gene found that is
linked to the phenotype or clinical condition - also known as a
"no primary finding" result. In this episode, our guests explore
the impact of a "no primary finding" result on families,
discussing the common experiences and expectations of parents and
patients who undergo that genetic testing, and the role that hope
plays in the experiences of children with rare and undiagnosed
conditions.


Today's host, Lisa Beaton, member of the Participant Panel at
Genomics England is joined by Dr Celine Lewis, Principal Research
Fellow in Genomics at UCL, Great Ormond Street Institute of Child
Health, Jana Gurasashvili, a Genetic Counsellor, and Louise Fish,
CEO of Genetic Alliance.


 


"I think it’s also really important to add that hope isn’t
necessarily lost when you don’t get a diagnostic result. And in a
sense, what can be really helpful is for genetic counsellors to
reframe that hope...sort of giving it a different context."


 


For more information on the SWAN UK project which supports
families with children that have been through genetic testing but
have not found a result following that genetic testing, visit
SWAN's website.

Read more about the study by Jana Gurasashvili and Dr Celine
Lewis: The disequilibrium of hope: a grounded theory analysis of
parents' experiences of receiving a "no primary finding" result
from genome sequencing.



 


You can download the transcript or read it below.


 


Lisa: Hello, welcome to the G Word. 


Lisa: I think in the back of my mind, subconsciously, I had hoped
that when we eventually got a diagnosis, it would – I don’t know,
bells and whistles, balloons going off, fireworks, etc. And then
the experience of a letter thumping on the doormat, and I
recognised the postmark quite quickly, and it was at that moment
I suddenly thought, “Oh gosh, I haven’t buried all these feelings
of hope.” Because I opened that letter with quite trembly hands,
and then this diagnosis or lack of diagnosis, you know, nothing
had been found, and it was a bit… I don’t know if it’s been
described as like a nail in the coffin experience, because I
really hadn’t realised I was still clinging to this hope all that
time, and then again it was, you know, another, “No, nothing’s
there.


Lisa: My name is Lisa Beaton and I’m a member of the participant
panel at Genomics England. On today’s episode, I’m joined by Dr
Celine Lewis, the principal research fellow in Genomics at UCL,
Great Ormond Street Institute of Child Health, Jana Gurasashvili,
a genetic counsellor, and Louise Fish, the CEO of Genetic
Alliance. Today we’ll be discussing the impact on parents with
children with rare conditions, who received a no primary findings
result after diagnostic whole genome sequencing. If you enjoy
today’s episode, we’d love your support. Please like, share and
rate us on wherever you listen to your podcasts.


Can I ask all of us here present to introduce themselves, please?


Celine: Hi everyone, I’m Celine, I’m a behavioural scientist in
genomics at UCL Institute of Child Health, and I currently hold
an NAHR advanced fellowship to look at the implementation of WGS,
or whole genome sequencing, in the NHS.


Jana: I’m Jana Gurasashvili and I’m a genetic counsellor at
Northwest Thames Regional Genetic Service, and prior to that I
was at Great Ormond Street, involved with consenting families to
the 100,000 Genomes Project, and I also have an ongoing interest
in the lived experience of patients and parents of genetic
counselling and rare disease.


Louise: Hi, I’m Louise Fish, I’m the chief executive of Genetic
Alliance UK, and we are an alliance of around 230 charities and
support groups that work with patients and families who have
particular rare conditions. We also run a really longstanding
project called SWAN UK, and SWAN stands for syndromes without a
name. And the SWAN UK project supports families with children
that have been through genetic testing but have not found a
result following that genetic testing. So, it’s clear they have a
genetic condition, but science hasn’t quite advanced far enough
yet to tell us what that means and what that will mean for their
child, and what that will mean for their family over the coming
years.


Lisa: And I personally can attest to the wonderful support that
SWAN UK can offer because, as the parent of a still undiagnosed
child, I have been involved myself with SWAN UK since my daughter
was around the age of three to four years old. It’s brilliant
being a part of my big SWAN UK family. We first realised that
there were some – I suppose something wrong with our daughter
when she was around two weeks of age, but it wasn’t something I
could specifically put my finger on. I couldn’t at that point
have taken her to a doctor and said, “I don’t know what’s wrong
but there’s something wrong.” I just knew in my heart of hearts,
probably because I have three elder children, that there were
issues, and things weren’t developing as they should. She cried a
lot, she screamed a lot, she never seemed to be comfortable in
any position when you held her, when she was asleep, when she was
upright. It didn’t seem to matter what you did, she was just a
rigid, stuck child, for want of a better word. And all my mum
senses were screaming, but it completely sounded ridiculous to
take her to a doctor saying, “She feels wrong.”


And I think that’s quite a SWAN UK experience, from chatting to
other families with similar situations. The parents just know
that there’s something not right, but it can be very isolating
not to be able to identify kind of where that starts and what it
is. In our case, it wasn’t until our daughter was nine weeks old
that things became much more obvious, that there were
developmental concerns physically and medically, and at that
point we went from my sort of mutterings that there was something
wrong but I wasn’t sure what it was, to a sudden hospital
admission with quite a shocking turn of events. From something
that had started out quite normally, as a routine visit to the
baby clinic, to suddenly being seen by a troop of different
paediatricians, and doctors coming in and out constantly, asking
different questions, and sending us off all over the building for
different tests and x-rays and imaging. And being given a partial
diagnosis that our daughter had a condition called
arthrogryposis, but it was clear that there was much more going
on than that, and we would need referring to many more different
fields. And that day really our diagnostic odyssey, for want of a
better word, began.


So actually, in terms of that diagnostic odyssey, many parents of
children with rare undiagnosed conditions experience this, and
when we agree to have genetic testing, we feel that we are going
to get these answers straight away, and that every appointment
that you go along to is going to be the one that brings you the
answers. But certainly in our experience kind of 15 years on,
that’s not been the story at all. Celine, can I ask you to
explain what the words no primary findings actually mean when a
parent receives that regarding their child?


Celine: So, there’s a range of different possible outcomes from a
genomic test. So, the results might provide a diagnosis to that
patient and family, or other situations, there might be a variant
of uncertain significance, so we don’t necessarily know if the
gene that we found, a genetic variant is the likely cause of the
condition, or we might find no particular gene at all that we
think is linked to the child’s phenotype or clinical condition.
So, that’s what we mean really when we’re sort of saying no
primary finding.


Lisa: Louise, would you be kind enough to explain what you think
the impact of no primary findings means to families like my own,
parents who don’t have a genetic likelihood cause, just a gene
thrown up to diagnose their child?


Louise: Yeah, I think it’s a huge challenge for families, and
you’ll obviously know that from your own experience. People go to
have genetic testing hoping it will give them some answers, first
and foremost, just to kind of understand, you know, what
condition their child has and what the likely impact that’s going
to be on their child and on the child’s life, and on the family’s
wider life. And I think one of the things that we really ask
genetic counsellors and geneticists to do is help people
understand before the genetic testing takes place that there may
be nothing found from it, so that that kind of expectation is
built in. Because people hope that they will get a diagnosis that
will give them answers about what the impact of the condition
will be on their lives. In a best-case scenario, access to a
particular treatment that might be a huge help for their child,
but at the very least, access to a range of services and support
for their child. So, that kind of diagnosis is often seen by
families as the key to unlocking a range of services and support
that will help them and their families at what is the beginning
of a lifelong journey.


And I think when families get no diagnosis, there’s a real
concern on behalf of families, a, that they don’t understand how
their child’s going to be affected by the condition. What we’re
really careful to say to families is, “Just ‘cos you don’t have a
diagnosis with a name, your child is still the same person they
were before. They still have exactly the same bundle of needs as
they had before, and you will still need to work with the NHS and
with wider services to make sure that they can access speech and
language therapy, and physiotherapy, and all of the services that
they are going to need and you are going to need to help them
live their lives to the full.” But I think that moment of not
getting a diagnosis is when people feel I think real – the
uncertainty continues, and uncertainty, we know, is a really hard
thing to live with, and the lack of clarity about which services
you’ll be able to access. So, I think psychologically it’s a
massive impact on the family not to have the answers that they
were looking for, or the key to the services that they were
hoping would be there.


Lisa: Thank you, Louise, yeah, I would definitely agree with
that. We had a no primary findings result in I think it was 2019.
It was a really bittersweet moment because my daughter’s list of
various different conditions kind of – by this point, named parts
of difficulties for her spans over sort of two pages of A4, and
yet on the letter back from the genomics service, it just says
that, you know, nothing causative has been found. And so part of
you is left wondering, well, how can there be all these different
conditions or difficulties, and yet there’s still nothing there?
And I know personally, I had comments when she was much younger,
every time a test came back, where people would say things like,
“Oh well, that’s great news,” and to some extent it was great
news that something hadn’t been found, but also if that hadn’t
been found, what was still out there? And that fear of kind of
the unknown was extremely difficult.


And also paradoxically, there was a sense of some very well
meaning people saying things like, “Oh well, if they haven’t
found anything then there can’t be too much wrong.” But yeah, I
have a child who is tube fed and on multiple different
medications, and cared for basically for 24 hours a day, so that
doesn’t really fit in with the picture of there not being very
much wrong from a personal perspective. And I think it can make
you as a parent/carer feel perhaps there’s a tendency to downplay
that there is an issue and that perhaps, you know, you’re making
it up, for want of a better word, and that sense of isolation
around that can certainly be problematic. Celine, if I can come
to you, that diagnostic odyssey, what are the common experiences
and expectations of parents and patients who undergo that genetic
testing from your perspective?


Celine: Well, I think sort of parents go into genetics testing
for a whole range of reasons really, and Louise has already
alluded to many of these. Ones that I’ve come across in my own
work include wanting to know why their child has a particular
health problem, so that that child can access the most suitable
treatments or therapies, or even access clinical trials. Even
relief from guilt for many parents, a validation that the parents
hadn’t done anything wrong during their pregnancy to cause the
child’s condition, and that’s hugely important really, to try and
get that relief from guilt. Also to know whether future children
might be affected by the same condition, and then more social
reasons really, for example, making contact with other parents
through support groups, or access to social and educational
support.


And I think there’s also a drive from many parents to feel that
they’re doing everything absolutely possible for their child. I
mean, particularly with something like the 100,000 Genomes
Project, it was really a sort of first of its kind project, where
patients were on a significant scale able to access this new
whole genome sequencing technology. So, many of the parents
taking part in that project felt like pioneers, and there was
really a lot of expectations around whole genome sequencing in
delivering a diagnosis for those parents who’d previously not
been able to get hold of one.


Lisa: Yes, I strongly can resonate with a number of the points
you made there, particularly the feelings of guilt. I must have
asked myself a thousand times whether, you know, something I did
do, something I didn’t do, something I thought of, something I
hadn’t thought of [laughter], all those questions that swirl
around, particularly in the small hours of the night when you
feel particularly alone. And yes, I can completely relate to
that. And also although SWAN UK is primarily for children and
parent/carers whose children don’t have a diagnosis, actually a
number of the parent/carers on there will have children with
diagnoses that are so very rare that absolutely, you know, very,
very little is known. They might be the only parent – the
diagnosis, for want of a better word, they may have received may
just be a series of kind of numbers and genetic dot-dashes,
forgive my layman’s terms there, but it may not actually help
them any further along in terms of feeling that they know
anything further or the direction of, you know, where that will
lead their children, and that can feel very, very isolating, I’m
sure, probably just as much for those of us who don’t have that
diagnosis.


Louise: Yeah, just to add to that, I think that’s absolutely
right, Lisa, and I just want to give a shoutout – at SWAN UK, we
tend to support families who don’t have a diagnosis at all, or,
as you say, a small number of families who do but have been part
of the SWAN UK family for so long that we’re very happy to keep
them because of the support they’re finding from other parents.
We work really closely with another of our members, Unique, who
are a charity that support parents in exactly the situation
you’ve talked about, where people have finally got a diagnosis
and it’s that kind of relief of having a name, but it’s a super
long name, and you find out you’re one of only three families in
the world with that diagnosis. And so although there’s a real I
think comfort for people, perhaps if you have a five year old and
you’re meeting a family who have a 13 year old and a family of a
19 year old, then you start to see a little bit about how your
child might develop, but there’s not enough kids affected that
you can be really certain about that.


So, it gives you a little bit more information, but not the kind
of wealth of information you were hoping for about how your
child’s going to be impacted by a particular condition, and what
the future might hold for you and for them. So, SWAN UK and
Unique very much work alongside each other to kind of support
families on whichever part of that journey they’re on, because
there’s still a huge amount of uncertainty for families with
those super rare conditions, as you say.


Lisa: Definitely, and I’m sure you’ll be familiar, Louise,
yourself if you get time to go on the online communities and
seeing the question that pops up quite regularly when somebody
has received a diagnosis of, “Can we still remain part of the
SWAN UK family?” And they very much use that word, family,
because I think they do feel that, although all our children are
different, there are children with physical, medical, cognitive,
a combination of all the above syndromes, conditions, etc, they
feel that kind of embrace of all being in a collective club of
rare and unique and undiagnosed, and that’s very comforting to
the members.


Louise: Absolutely, yeah, I think that sense of belonging and
being able to reach out to other families that you’ve been on
that journey with for many, many years. You know, many of our
families join when their children are like one or two, and
they’re still with us when, you know, their children are 26, 27
[laughter], and that sense of having that community and that
family and that belonging is really, really important to people,
I agree. It makes a big difference psychologically to be part of
a community you can reach out to and ask the questions that
perhaps you can’t ask to other people.


Lisa: Celine, can I ask you how many patients for the 100,000
Genome Project have had a no primary findings diagnosis back?


Celine: Well, back in 2021, there was a paper published in the
New England Journal of Medicine, which reported that, in the
initial pilot for the 100K, a diagnosis was found for around 25
percent of rare disease participants, and other studies looking
at the diagnostic yield of whole genome sequencing have put the
number anywhere between 25 percent to 55 percent, depending on
the clinical indication. And we know that even already from the
100,000 Genomes Project, this pioneering project has led to more
than 6,000 diagnoses being identified, and that number will
obviously continue to go up as they explore the data and gather
new insights. However, that still obviously leaves a significant
number that won’t get a result from whole genome sequencing, as
many as half of those rare disease patients, and that was really
the basis of the study that Jana and I worked on.


So, we felt that there had been so much research really looking
at the experience of parents who do receive a genetic diagnosis,
and that a lot of attention rightfully does focus on the amazing
successes of the 100,000 Genomes Project and genomic medicine
more broadly, but actually that there is a considerable number of
patients and parents and families who don’t get a result, and we
felt that it was important that we also focus on those parents
and patients, and try and understand their experiences.


Lisa: Yes, you can feel, if your child, for example, is under
multiple different care specialists, that it can be quite hard,
when you’ve just got this list of different names of things that
are wrong, that you feel very much still out on the limb and
forgotten about. But it’s clear that, from your work, you’re
identifying that and pointing that back to the specialists, the
consultants, to remind them that these parents and these children
are still finding their ways through. Can I ask you, Jana, the
study that was conducted, what would you say the main things from
that study told us? Can you describe some of the emotions
experienced by the parents, and what challenges that they have
faced along that receiving the no primary findings diagnosis?


Jana: Yes. So, many participants really felt very strong
disappointment and sadness on receiving that no result, and for
many, it kind of reflected the feelings they had had when they
first realised they had a child and there was no diagnosis for
their condition. And as Celine said, this was such a new
technology that people had invested a lot of hope in, and so many
felt that it had been their last chance of finding a reason for
their child’s condition, and that they’d come to the end of the
road with that no primary finding result. And, well, one person
described it as another door shut. And people talked about the
actual toll taken, the emotional and physical toll, and one
person described feeling low for several weeks following the
result. And some talked about the timing of the result. Somebody
got it as a letter just before Christmas, and so their whole
family holiday that they’d prepared was marred by getting that
news just before Christmas.


And it often seemed to leave parents feeling isolated and unable
to contribute to normal parental roles, such as going to parent
groups, etc, because they felt that other mothers particularly -
as it’s mothers we were speaking to, other mothers, their
experience of motherhood was so incredibly different to their
own, and they felt a lack of support. And one parent actually
talked about wanting to lock everyone in the house just to escape
the feeling of judgement and pity from outside the front door.
And some parents talked about finding it hard when other people
would post on support groups that they had got results from the
100,000 Genomes Project, which was very difficult. And some
talked about hope as finding it hard to keep hopeful but needing
to keep hopeful. So, they talked of hanging onto a little bit of
hope, as though that was quite an intense thing, which I think,
Celine, you’ll agree, that made us able to kind of identify that
hope was really part of a coping mechanism for this whole process
of going through this diagnostic odyssey.


Celine: Yeah, people sort of talked about not wanting to let go
of hope and the importance of hope, and that without hope, there
was no sense of wanting to continue this journey of trying to
find a diagnosis, and that it was still very important to people.
And I think that parents did understand that, even though a no
primary findings result now, that doesn’t necessarily mean that
they won’t get a diagnosis at some point in the future. So,
there’s obviously the opportunity to do future reanalysis of the
genome, particularly as we understand more about the function of
different genes, and as new genes are added to many of the panels
that we’re using in whole genome sequencing. So, I don’t think
not finding a result means that there is no hope in these
circumstances, but for many parents, they did talk about hope
being too painful, and not wanting to be let down again, and
really preferred to focus on the here and the now rather than
necessarily focus on the future.


Lisa: Yes, I can only speak from my own experience here, but I
think I primed myself to actually forget about going on the
100,000 genomes sequencing because, having undergone genetic
testing for certain conditions that they were quite convinced my
daughter had from around the age of four months through to around
the age of three years, I’d gone to so many appointments and
thought, “Oh, this’ll be the time that I turn up and somebody
will tell me this is what is the diagnosis.” And when I then
joined the 100,000 Genomes Project in 2015 with my husband and my
daughter, the genetic experience, the discussions that we had at
the time were very helpful in that it was made quite clear to me
that potentially we wouldn’t get a finding, and actually that any
information that did come forward was perhaps unlikely to be
hugely beneficial to our family at that point. So, I was quite
clear what potential finding would mean to us.


But I think in the back of my mind, subconsciously, I had hoped
that, when we eventually got a diagnosis, it would – I don’t
know, bells, whistles, balloons going up, fireworks, etc. And
then the experience of a letter thumping on the doormat, and I
recognised the postmark quite quickly, and it was at that moment
I suddenly thought, “Oh gosh, I haven’t buried all these feelings
of hope.” Because I opened that letter with quite trembly hands,
and then this diagnosis or lack of diagnosis, you know, nothing
had been found, and it was a bit… I don’t know if it’s been
described as like a nail in the coffin experience, because I
really hadn’t realised I was still clinging to this hope all that
time, and then again it was, you know, another, “No, nothing’s
there.”


And I think because of the work I’ve undertaken with SWAN UK as a
volunteer, and being quite involved in wanting to sort of educate
myself and learn more, I did understand that, even though we had
no primary findings, it didn’t mean that the study, everything
was closed to us. It didn’t mean, you know, that things won’t
still be looked for. But equally, at the same time, it just meant
that we had nothing yet to pin anything on at that point. And I
think it’s quite hard to pick yourself up and dust yourself off
again, to be like, “Okay, we’re still here, we’re still circling
that drain,” as it were.


I think actually that takes us on quite nicely really, about what
role hope has in the experiences of a child with rare and
undiagnosed conditions. And again if I can just say that there’s
hope and there’s realism, and somewhere along the way, if you’ve
been on the journey for quite a long period of time like
ourselves, you have to try and find a way of living with that
hope and realism all at the same time. So, we’re still hopeful
that one day we might get some answers, but we’re realistic that
day to day we need to focus on the difficulties or the
experiences that my daughter has, so that we can manage to give
her the skills to live her life to the very best of her
abilities. Certainly, that’s our experience. And also I think if
I’d let myself dwell forever on not having a diagnosis or a
pathway specifically for that, it would have been quite difficult
to carry on, pick ourselves up every day. What would you think
about the role of hope there, Louise? What would you say your
experience is from chatting to fellow parent/carers?


Louise: Yeah, I think you’ve described it really eloquently and
better than I’ll be able to do, but when we talk to people, the
phrase I always have in my head is kind of hope for tomorrow and
help for today are the two things that people are looking for.
So, making sure that that hope for tomorrow’s still there both in
terms of, you know, the NHS being really clear that it will
provide support for individuals without a diagnosis, and there
may be opportunities for reanalysis in the future as science
makes future progress. And, you know, there is progress being
made so fast at the moment in genomics and that’s really welcome.
So, making sure that people who’ve already had whole genome
sequencing but not found anything continue to have access to that
potential reanalysis I think is really important.


As you’ve rightly said, Lisa, as well, thinking through in terms
of hope for tomorrow, the opportunity to take part in clinical
trials and to make that as easy as possible where treatments are
being delivered, to have the opportunities to take part in trials
for non-condition specific treatments, whether that’s for
epilepsy, which affects people across a whole range of
conditions, or sleeplessness, which affects people across a whole
range of genetic conditions. You know, there are both trials that
only people who have a particular condition can take part in, and
trials that are open more broadly, so making sure those
opportunities are available as well, so that people have that
kind of hope for the future.


But alongside that, I think it’s really important for the NHS to
be clear with people about what help for today will continue to
be available, and so we are working really hard with the NHS to
emphasise the fact that when no diagnosis is possible, the NHS
still needs to be clear to people about how they will be
supported, whether that’s through the genetics team or a
particular discipline, perhaps the one that is the closest fit
for their child’s biggest need, whatever that may be, that they
can still access more joined up care. So, you know, who is the
person in the NHS, if you don’t have a diagnosis, who’s going to
help you secure referrals to speech and language therapy, to
physiotherapy, to learning disability nurses, and to the package
of care that your child may need.


Who is the clinician, if you don’t have a clear diagnosis, who’s
going to be the person with the authority and the confidence to
lead the multidisciplinary team, maybe up to 30 healthcare
professionals who are going to support your child. You know, who
is going to be the lead clinician that’s going to pull that
multidisciplinary team together and make sure that your child’s
not being prescribed stuff that’s contraindicated, or that’s
going to help one element of their condition but make another
element worse. So, we are really trying to work with the NHS to
make sure they’re thinking through, where will that support be
for the family in terms of their healthcare.


And alongside that, you know, many wider services like schools or
social care or employers welcome the chance to talk to a
geneticist or a genetic counsellor or nurse to understand what
adjustments they might need to make for someone who clearly has a
genetic condition but doesn’t have a clear diagnosis. And so
we’re trying to kind of make sure the NHS is both focused on the
kind of science side and making sure that the hope for future
findings is there, but also the help side, and making sure that
the right package of care is still available for families who
clearly have a genetic condition.


Lisa: Actually Louise, yeah, you’ve really summed it up
excellently there, and whilst I am hugely grateful to the NHS and
the various services, I can say, hand on my heart, my daughter
has a huge number of professionals involved, both from the health
side of things and social care side of things, and actually the
person that kind of holds all that together is myself. And
because we’re under multiple different teams, every time a new
medication, for example, is prescribed, I need to go back to our
lead team, which in this case happens to be neuromuscular, and
check that, for example, if gastroenterology have prescribed a
medication, that it’s not contraindicated from a neuromuscular
side of things and so forth.


It’s all a bit like having sort of interlocking parts of a
jigsaw, but perhaps no picture to follow [laughter], and that can
be quite an isolating experience. And certainly, having chatted
to fellow parent/carers, I know that’s their experience as well.
And I imagine, Celine and Jana, you found sort of similar
experiences when conducting the research.


Celine: Yeah, so my PhD actually was focusing on the sort of
journey for parents as they go through the diagnostic process,
and one of the things that came out really strongly from that
body of work was how the parents were really carving their own
care pathway, how they had to sort of push and fight to access
services, but at the same time were the gatekeepers for their
child’s health. Having to make sure all the various teams and
clinicians were kept up to date with all the different tests that
they had and all the results. And, you know, at times, this could
be really frustrating for a lot of parents, ‘cos they had to keep
repeating their story over and over again, particularly ‘cos they
didn’t have a diagnosis. So, these parents really were having a
very different parental experience to many of their friends and
family, because their experience of being a parent to a child
with an undiagnosed condition was really sort of as being a
patient advocate, and as having to push and fight to access
services.


Lisa: Yeah, it’s quite a unique experience. You are the
specialist for your own child in that sense, I think would be the
way I’d describe it. And I suppose over the years, I’ve got so
used to sort of trotting out different medical explanations in
terms that you can almost sound like you know what you’re doing
[laughter]. And a few times when I’ve been at medical
appointments, and perhaps we’ve met a new specialist or
consultant, they’ve said, “Oh, what’s your field? What’s your
area of expertise?” And actually you just think, “No, I’m just a
specialist in my own child” [laughter]. But that’s quite an
empowering feeling actually, so I guess that plays back into the
feelings around hope and expectation, even with having an
undiagnosed child.


Lisa:    When I was recruited to the 100,000 Genome
Programme, we didn’t actually as a family receive genetic
counselling specifically, and I know that this is something that
is incredibly important to many families, and how that can
support you sort of going forward. We were quite lucky in our
experience in that we knew that our daughter was definitely going
to be our last child, so we didn’t have the thoughts and
insecurities around potentially what it might mean for any future
children that we had. But certainly as my daughter has got older
and she’s asking her own questions, and our older children are at
a stage in life where they’re looking at potentially having
families in the future, I know that those things have come up,
and we’re just still exploring what that will mean in the bigger
picture. But can you tell us, Jana, really what can genetic
counsellors do to help parents feel less isolated and better to
cope with the uncertainty surrounding their child’s condition?


Jana: Yes, well, I’m sorry to hear you didn’t have any genetic
counselling prior to going on the 100,000 Genomes Project,
because that consent conversation right at the beginning, before
the whole genome sequencing, is really important. It’s important
to know what the range of outcomes may be, so that it may be that
you might get a result, you might get a variant of uncertain
significance, or you might get no result. And parents in our
study did suggest that their sense of isolation when they got a
no primary finding result would have been alleviated if they’d
known how many were not getting results. So I think in the longer
run, it’s 40 percent perhaps received a result, so that’s 60
percent that didn’t receive a result, so those parents were not
alone, but they felt very alone. And some suggested if they’d
just had a leaflet really explaining that, and explaining that
they’d still contributed to research and that that had been, you
know, a good outcome in a sense, then they would have felt better
about it.


So, a lot of work can be done before the testing really, to
explore how you might feel on that range of results, and then
that way sort of prepare parents for how they’re going to feel,
and perhaps that helps them to have things in place, to know that
it might be a vulnerable time with that letter, although that was
particular for the 100,000 Genomes Project, to get the result in
a letter in that way, and as you described, after such a long
time, that you’d been able to forget that you’d been on the
project. But to actually be a little bit prepared that it make
take its toll on you might actually help with preparing oneself.
It also might be helpful to include ways of promoting ways to
enhance health and wellbeing for parents in terms of practical
support, such as those things that you’re already attempting to
access, like the respite services, school support, support
groups, and thinking about psychological wellbeing and ways of
managing stress, psychological support for parents, and possibly
spirituality based resources as well.


And focusing maybe on what is known about the child’s condition
even without a diagnosis, so what’s likely to be beneficial, and
support parents in actively coping, such as what research they
might be able to access, and continued medical support. And also
actually having a named person within the genetics service, so
they have someone to go to for any follow-up that has a name, and
so they don’t feel isolated from the genetic service. And
signposting to those external resources, such as SWAN UK, can be
very important as well, of course.


Celine: I think it’s also really important to add that hope isn’t
necessarily lost when you don’t get a diagnostic result. And in a
sense, what can be really helpful is for genetic counsellors to
reframe that hope, if you like. So, one thing that we talk about
in our paper is that it might be useful for health professionals
to ask a question such as, “In light of the new information that
we now have from the whole genome sequencing result, what are you
hoping for now?” So in a way, it’s sort of reframing that hope,
sort of giving it a different context.


Lisa: Definitely, and I think one of the things as well is that,
because potentially for when parents were first recruited to a
study such as the 100,000 Genome specifically in this case, that
it might be quite a length of time between that initial
recruitment and when the actual result comes out. And of course,
in that time, with the advances in genetics, it’s sort of
somewhat of a Pandora’s box really, isn’t it, in that we’re
almost kind of finding the information out quicker than we
actually know how to process it and what it potentially means. So
actually if there’s a genetic counsellor available to speak to
those parents, or for those parents to be signposted to somebody
who can say, “Well look, since you were recruited, actually this
is happening, that’s happening,” or, “These research projects are
happening,” personally, I can say that is going to be really
helpful and handy, and would have been really useful. I just know
that for myself anyway and my family, that if there was a leaflet
or something that had given me a way of knowing how I could
contact somebody in the future, that would be really helpful.


What ways do genetic counsellors use in maintaining a delicate
balance between not creating false hope but also providing
meaningful support to parents? What would you say around that,
Jana?


Jana: I think as we’ve already touched on, it’s that managing
expectations from the outset when the test is offered. So, not
generating too much hype or excitement, but setting those
expectations, giving that information about the diagnostic yield.
Also, informing parents that what people do experience has been
described as a rollercoaster of emotions. It’s normal. You might
also want to explore people, not only what they’re hoping for,
but also the outcomes that they might be fearing, and giving them
a chance to voice those, because they can be very powerful things
as well. A diagnosis might not be what you want to hear, so there
can be a lot of ambivalence around wanting a diagnosis when it
might actually be a life limiting condition, that you didn’t
really want that certainty.


And also helping parents to explore how not receiving a result
might feel, so that they’ve actually rehearsed it a little bit,
and where they might go to when they need a bit of extra support.
So, they already know, “I go and talk to my friends, that’s where
I get my support from,” so that they’re kind of ready for it, and
that might help them with that sense of isolation, but also
validating these feelings. So, it’s okay, it’s okay to have that
dip, it’s okay to feel, that it’s something that many people
experience. And creating a safe space for people to feel that, so
if they want to talk to a professional or a friend, that those
feelings are validated.


And in that way, kind of with that pre-counselling really,
helping parents to develop their own set of resources, so they’ve
got those to draw on. And as you’ve mentioned, Lisa, it’s like
having your own resources also helps generate that feeling of
empowerment and control. And as Celine has said, it’s really
facilitating parents through that passage of reframing what
you’re hoping for, reframing what the future looks like, if you
had one picture of a future. You need to become comfortable with
the future you’re now looking at.


Lisa: Thank you, Jana. Louise, if I can ask you really, we’ve
already touched on the role that SWAN UK can play for parents
dealing with undiagnosed rare conditions, but perhaps if you
could home in on that and explain in more detail the main focus
of SWAN UK, and what that can do for parent/carers.


Louise: So, what SWAN UK primarily does is bring together parents
who are in a similar situation. So, we have a team of amazing
parent representatives, who Lisa is one, who help us shape the
support that SWAN UK can provide, and really make sure that it’s
based on a really strong understanding of what it’s like to be a
parent of a child with an undiagnosed genetic condition, and an
understanding of that kind of expertise that parents who have
been on that journey themselves will bring. So, we have a series
of Facebook groups. Some of them are for different regions, so
people come into contact with other parents in their area who are
going through similar circumstances. Some of them are more around
age. So, you know, we have Facebook groups for parents who are
waiting for a diagnosis or have got a new diagnosis, and then we
have a group called SWAN Graduates, which is for children who are
older and over 18, so their parents can come together and share
their experiences.


So, it’s really to help parents be able to talk to one another,
to share their experiences, to support one another, and often to
ask for advice. They’re often kind of practical questions about,
you know, “My child needs this kind of wheelchair, has anybody
been able to source that from somewhere?” “My child’s having real
difficulties eating at the moment, can anyone give some advice on
this particular challenge?” “This thing someone else has faced,
how did you approach it? Where did you reach out for support?”
So, that peer to peer advice and support is really at the heart
of SWAN UK.


And then what we try and provide around that is access sometimes
to information events, where there’s particular issues that are
affecting a lot of SWAN families. So, we hope over the coming
year to have a series of information events targeted at families
with children who don’t have a diagnosis, and some of it is just
trying to have social events and bring people together again.
We’ve had, for example, an active dads group in Wales, who’ve
been bowling and wanted to go axe throwing, and really they just
want to come together with other dads who are in the same
situation, and being able to talk to one another and provide
emotional support to one another.


So, that’s kind of the nub of SWAN UK and what we do, and then
alongside that, that kind of fits in with Genetic Alliance’s
wider goal, which is much more around campaigning for improved
services. So for example, the Genetic Alliance UK team has worked
really closely with commissioners in Wales, who actually
commissioned the first SWAN clinic, which is in Cardiff. That was
a two year pilot, to see what support could be provided both to
help SWAN families get a diagnosis, but far beyond that, to make
sure that the care for families who don’t have a diagnosis is
better joined up. And that we feel has been a real success.
Again, there hasn’t been a really high diagnostic yield, there
have been very few new diagnoses, but the support provided to the
families who are in contact with that clinic, in terms of helping
them access better joined up care both from the NHS and from
services more widely, has been brilliant. And we’re currently
working with NHS England in the UK, who are exploring an
opportunity to commission two SWAN clinics in England.


So, that trying to kind of improve services, and then the third
aspect of that is just working generally with the new genomic
medicine service alliances as they emerge across England, to try
and make sure they are thinking through what support they will
need to continue providing to families who’ve gone for whole
genome sequencing in future, not through a research project like
100,000 Genomes, but just through routine clinical practice and
routine clinical diagnostics, what support will they need to
provide for families who go through that process and don’t get an
answer. And that won’t change the support they will need from the
NHS. It will just mean that perhaps that clinic needs to play a
more active role in helping them access those services. So, all
of that kind of campaigning to have better services for family
who have an undiagnosed genetic condition continues as well.


Lisa: So, I think one of the things really just to finish off
today, is of course looking at the future. Considering
advancements in technology, would you say that future reanalysis
of the 100,000 Genome Project is going to yield additional
insights? Celine, can I ask you to comment on that?


Celine: Yes, absolutely. As we understand more about the role and
function of different genes, and as new genes are added to the
panels, we will definitely be able to provide a diagnosis for
more parents and more families. But I think we don’t yet
necessarily know exactly what that reanalysis will look like, and
it’s not really clear yet how this will work in practice.


Lisa: And Louise, would you have anything else to add to that at
all really?


Louise: No, I think it is just that hope for the future and kind
of help for today. I think the NHS needs to be equally clear
about, you know, there’s some amazing investment by the UK
government in genomic research, and that’s brilliant and we want
that to continue, but equally we want the investment to be taking
place into routine clinical services and diagnostic services, so
that we can talk to people both about the hope of potentially
getting a diagnosis in future, but making sure that the help
continues to be available for as long as they don’t have a
diagnosis, and that help for families who don’t have a diagnosis
is going to be just as important. And what we try to ask for is
both real clarity around what the NHS can provide, and really
clear signposting to organisations like SWAN for families that
continue to not have a diagnosis. And again, just to give an
equal shout out to Unique, who are able to support families who
have an ultrarare diagnosis, where perhaps they’re the only
person in the country with that particular diagnosis, or one of a
handful of families around the world. Signposting to that peer to
peer support will continue to be a really important part of the
process as well, so that families can help one another, learn
from one another, and just give each other support that they are
kind of sharing that same journey and walking alongside one
another on that journey as it continues.


Lisa: And bringing this podcast to a close, can I just ask you
really, any final thoughts, anything that you would sum up from
your experience of researching the no primary findings and where
we now are today?


Celine: I think the main thing for me is just to sort of make it
clear to parents that a diagnosis isn’t necessarily a magic wand,
even though it is obviously very important to a lot of parents.
But that even without a diagnosis, we still have the opportunity
to manage patients’ symptoms, and often a diagnosis doesn’t make
a substantial difference, because parents are sometimes left with
a lot of uncertainties and a lot of unanswered questions. So I
think, and as Louise and Jana have said before, it’s really sort
of on focusing what we do know, and thinking about what we can
offer and what support we can provide to parents and families
even without a diagnosis.


Lisa: Thank you very much to our guests today, Jana Gurasashvili,
Celine Lewis and Louise Fish, for joining me as we discussed the
impact of a no primary findings result. If you’d like to hear
more like this then please subscribe to the G Word on your
favourite podcast app. Thank you for listening. I’ve been your
host, Lisa Beaton. This podcast was edited by Mark Kendrick at
Ventoux Digital, and produced by Naimah Callachand.