THIS TRANSCRIPT WAS AI-GENERATED AND MAY CONTAIN ERRORS!

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Introduction and Guest Introductions

[00:00:06] Irina: Hello and welcome. This is the final episode of our genomics series. My name is Irina Varlan. I'm a clinical pharmacist. And together with my guests today, we're gonna try and cover some of the topics we haven't discussed so far in the first five episodes of the series. But before we start, could you please introduce yourself?

[00:00:30] Pooja: Hello, I'm Pooja Dasani. I'm a lead genomic counsellor for North Thames GMSA and a principal genetic counsellor based at Great Ormond Street Hospital. 

[00:00:39] Anwar: Hi, I'm Anwar Khan. I'm a GP, a frontline GP and trainer and one of the GP leads for Northern North Thames GMSA. 

[00:00:47] Irina: Thank you both. 

Recap of Previous Episodes

[00:01:01] Irina: We've had five episodes so far discussing genomics and genetics.

[00:01:06] I was thinking we could do like a mini recap before we move on to some of the topics we plan on touching today. I'm guessing both of you have had a chance to listen to all the episodes and Anwar you were a guest on a few of the other ones. Is there anything in particular that stayed with you from the episodes you did or from the ones that you listened to?

[00:01:24] I 

Importance of Genomics in Primary Care

[00:01:24] Anwar: think anybody in primary care when they're seeing patients need to think genomics. Patients deserve the best care possible and there's lots of advance in genomics that we need to avail our patients for. 

[00:01:36] Pooja: Okay, Pooja? I absolutely agree. I think, you know, we've always thought about genetics and genomics as a niche subject that sits outside of everyday care.

[00:01:46] But in reality, it's a part of every health condition, every sort of patient that we see in some format. So it's worth thinking about it each time and does it apply? 

[00:01:56] Irina: I see. Thank you both for your input. I think for me, um, I suppose what stayed with me particularly was the breast cancer case from episode four, I think, and how important it was to be aware of what's available in primary care when the patient first comes to you and identify early.

[00:02:13] And how important family history is basically how important it is to listen to the patient to make sure you highlight all the relevant information. And for a few good years, genomics was very much a thing for specialized fields. So you, you heard about it in, in oncology, in rare diseases, but it wasn't necessarily something you had in mind when you had a day to day encounter with a patient.

[00:02:36] It wasn't something so commonly. Discussed as it is now. 

[00:02:41] Anwar: Genomics is, uh, is often being taught at med school as part of biochemistry. And yet, really, there's a lot more practical applications. And remember, in primary care, we deal with families. Family history should be natural to us, really. And I think it's really important that we're curious about our patients and their families.

[00:03:03] And we actually encourage our patients. to think, uh, genomics as well. Uh, any thoughts, Pooja, what do you think when you come across, I mean, you obviously see the ones that we've referred to, don't you? 

[00:03:16] Pooja: Yeah, absolutely. And I think, you know, primary care, you're so used to listening to so many different stories from individual family members.

[00:03:24] It's just kind of thinking about those in the context of what's applicable and what fits, um, is, is that sort of, specialist knowledge that you need, isn't it? To condense all of that information that you gather in your uh, very quick appointments and how do you put it across and get that referral across when it's appropriate or even when it's not appropriate to kind of think about, you know, why is the patient anxious around genomics and what is it that they've heard that's suddenly making them think Oh, I really need a referral.

[00:03:54] Anwar: Interestingly, in the late 80s, when I was a proper geneticist, that I used to learn a lot from my patients about their conditions rather than the textbooks. Um, but when we're talking genetic referrals, Pooja, just remind me of your audit that generated the GP leads to develop a genetic referral form.

Genetic Referrals and Forms

[00:04:12] Anwar: Should we just talk about genetics referral form? Because that might actually give a clue as to what type of things we can manage ourselves with. And what type of things we need, do need to refer to specialists like you Pooja, what do you think? 

[00:04:24] Pooja: Yeah, absolutely. I mean, it kind of came out of a conversation that we're kind of having now, isn't it?

[00:04:28] It was that kind of a little chat where we were talking about our frustrations in, in care where, you know, we were getting a number of referrals from primary care and clinical genetics that weren't quite appropriate. And similarly, Anwar, I know you were saying that You know, you're not always sure and you know, which ones you can deal with and which ones need to come to clinical genetics.

[00:04:48] So, I suppose what we did as a part of that was really audit the referrals that we were receiving for primary care and look at what the themes were, you know, what was happening? What was the information that was there? either available or missing, and actually what your frustrations were as well at the same time to try and address those.

[00:05:08] Um, and jointly we've developed some referral forms, haven't we, Anwar, that sit within the practice. 

[00:05:15] Anwar: Absolutely. And it's based on common ways of referrals because actually a lot of our data is on the computer system so it can auto populate. So all the healthcare practitioner needs to do, whether it's a nurse, pharmacist, GP, is think genomics.

[00:05:29] Once you've thought genomics, get onto the referral form and then you can say, is it a general genetics referral or a cancer genetics? And on the form, you do have. Should we say suggestions as to what's appropriate or not. So for example, if you've got someone with alpha 1 antitrypsin deficiency, that's not appropriate genetics and actually there is a hyperlink.

[00:05:51] You click on that and you can test for that in general practice. The other things we can do in general practice are familial hypercholesterolemia, isolated arrhythmias and cardiomyopathies. We probably need to go to the cardiac condition people. Haemochromatosis, general practice, but you can, uh, gastro and haematology can do that.

[00:06:10] Haemoglobinopathies, again, through haematology. Haemophilia through haematology. Recurrent miscarriages through gynae. But the rest of them, I think we refer to you in genetics. 

Family History and Genetic Testing

[00:06:22] Anwar: And I think one of the things I'm finding really helpful is asking my patients. to draw their pedigree and, and we then attach it on, which has been quite good fun by the way.

[00:06:34] I've done a couple that way. My patients are beginning to think, Oh, that's how you draw it. So I've been teaching my patients how to draw family pedigree. 

[00:06:40] Pooja: Oh, it's quite a, it's quite an interesting thing these days, isn't it? People come with their family histories drawn up through different tools that they've been using online.

[00:06:48] And they've been digging a lot about their family history, which is great, but also obviously raises anxiety as well at the same time, things that they didn't know about. I suppose just to add to what you were saying is the other condition that we can test for in primary care is to carry a test for cystic fibrosis.

[00:07:02] And that's a new addition to the national genomic test directory. And I'm sure you've heard about the genomic test directory over the last few episodes. And that's kind of one of those iterative processes, you know, it constantly changes. And cystic fibrosis is one of those things that was added to the test directory not that long ago. As a condition that can be tested in primary care. 

National Genomic Test Directory

[00:07:20] Anwar: Actually, that's a really good point about the National Test Directory because actually it does ensure equitable access to testing irrespective of where you live. One of the things that we're looking at researching into, um, EDI issues in genetic testing because it, it is possible to end up with a group of people being afraid of genetic tests or not being aware of it and their higher education.

[00:07:43] But maybe we can talk about cultural differences later in our talk. But yeah, I think National Test Service is really good. The other thing, Pooja, what do you think of G-notes? 

[00:07:52] Pooja: That's such a fantastic quick resource to use now, isn't it? Um, I don't know whether, you know, whether you've looked at it, Irina, have you, have you ever tried it?

[00:08:03] Irina: No, I haven't. No. 

[00:08:04] Pooja: Yeah. So G, G notes is a great set of resources that's been developed by the genomic education program in conjunction with clinicians who are experts in the conditions. Uh, and these are quick resources that you can use, uh, whilst you've got a patient in front of you as a, as, as a way of kind of working out what. Do you need to do when somebody mentions a condition that might be something you've probably never heard about in the past, or you're not quite sure what you're doing with them, or even you're working out. Is this actually relevant? So it's a fantastic resource. Thank you. 

[00:08:36] Anwar: Pooja, I wonder on this note whether or not we can talk about if a patient comes and says my niece has got cystic fibrosis, because that we can test ourselves.

[00:08:45] Would it be helpful just to go through as an example of what we can do and, and it maybe then lead on to how can you read the result? Because I think again, just like we order full blood count, we learn how to read it. Would that be an example that we can go through? 

[00:09:01] Pooja: Sure, certainly. And actually, that's a really good point that you mentioned about the referral form. And it's quite a, you know, you're just an easy, just check by check, you know, does it meet one? Does no, does it meet two? No. And all of this is built in using the test directory. So it's quite intuitive using that actually, is this person going to be eligible for a referral based on a test that they can have, but the two main criteria broadly are does the individual have a family history of a condition like cystic fibrosis as Anwar just mentioned or any other condition?

[00:09:32] Or does this person themselves have a genetic condition or a suspected genetic condition? And they are the two broad criteria that Um, and they can be narrowed down by asking further questions or possibly drawing a family tree like Anwar has been talking about. 

[00:09:46] Anwar: On that note of the National Test Directory, the form actually has the National Test Directory codes.

[00:09:52] So for example, personal history of breast cancer, it's got a hyperlink to the National Test Directory of R208, for example, and you just click on it. You don't have to remember anything. You just click on the hyperlink is what we're saying. So, So Pooja, let's just go back to, uh, the patient coming in, and you have to pretend you're a GP now, because I'm going to get you to go through the thing.

[00:10:12] Pooja: That's a bit of an upgrade. 

Cystic fibrosis example

[00:10:15] Anwar: So, patient comes in and says, my niece has got cystic fibrosis, what can I do? So, what are the facilities available for the GP to do? 

[00:10:23] Pooja: So I suppose the first question that you're asking is, You've got a patient, you're saying, my niece has got cystic fibrosis. Has the patient had genetic testing?

[00:10:33] Do we know what the gene variants are? That all the gene changes are that cause the cystic fibrosis. And the reason that's really, really important is because the cystic fibrosis gene is quite long and there's lots and lots of variants that can occur within the cystic fibrosis genes. And they're also variable.

[00:10:52] So not all variants will cause classic cystic fibrosis. There can also be sort of adult onset or milder cystic fibrosis. So you kind of need to know a little bit about it to be able to offer the right test. You then ask the question about family history in the sense of who else in the family has been tested.

[00:11:09] Because Yes, you can offer the test to the patient that's in front of you, but in reality, there are a number of intervening relatives that would be more appropriate to test first. Because if you did test your patient first, and you found that this patient was a carrier, you inadvertently actually reveal the results of the intervening relatives who haven't had a chance to have a test.

[00:11:31] But once you've done all of that, and actually the appropriate family members in between have been tested, yes, you can offer a blood test to your patient with the appropriate consent that you'll be offering them a carrier test for common cystic fibrosis gene variants, assuming that the variant in the family is one of those.

[00:11:49] And the reason we do that is because, actually, as I said, cystic fibrosis gene is rather long. We don't sequence the whole gene fully because it's not necessary. 50 gene variants is enough, um, and usually covers a very significant proportion of all cystic fibrosis gene carriers. So, and that depends on the ethnicity of the person.

[00:12:11] Anwar: That's why it's important we record the ethnicity. The other thing Pooja, I noticed on the results bit, when we get it, they don't say, They say risk drops from that to that not yay or nay. Can you explain why we don't do that? 

[00:12:27] Pooja: Yeah, so it usually uses the words at the risk has been reduced from usually if you're talking about a patient who was white British.

[00:12:36] The risk has been reduced from 1 in 25 to maybe 1 in 72. And that depends on how much information about the family history you've provided. And the reason for that is because what we're doing is we're offering testing for 50 of the most common gene variants. We're not doing a full sequence, so we're not looking at every single gene variant in the cystic fibrosis gene.

[00:12:55] So they can never say that the person's never a carrier. It's just reducing the risk because we've looked at all the common ones and they weren't present. 

[00:13:02] Anwar: So, and the other thing is about timing, isn't it? Uh, I think, you know, when people come with that, when they're pregnant, that makes things a little more hairy, doesn't it?

[00:13:11] Whereas if they're not pregnant, but we can order urgent tests, can't we? 

[00:13:15] Pooja: Yeah, absolutely. So you're right. Ideally, we want to see people that You know, how are planning a pregnancy rather than pregnant because you've got a bit more time for that decision making to be able to offer the right test at the right time and more options available.

[00:13:33] But, of course, if people do come to you when they're pregnant, it's, you know, you can offer an urgent pregnancy test. carrier test, and that can be done sort of as quickly as sort of a turnaround of two weeks rather than the usual four to six weeks. So yeah, it's, it's quite important to, to have those conversations early enough, but of course, most people think that it's not relevant until, until they do become pregnant.

[00:13:55] Anwar: Absolutely. Irina, I mean, we use things like alleles and polygenic scores. Are you happy with some of those terms or do you want our expert Pooja to explain? 

[00:14:06] Irina: Yes, I, um, wanted to jump in and ask about that, but I wanted to first ask a question about our imaginary patient. You mentioned that there would be a number of relatives that would be more suitable to be tested first before our patient.

[00:14:21] It obviously touches on a few. Topics here, because you could have a patient choice to test or not to test. Maybe some relatives aren't interested in finding out, they would like, you know, life to surprise them, rather than knowing exactly what disease could happen or could not happen to them. But what do you do in this case if your patient really wants to know, and maybe, let's say, the other three or four relatives don't want to test, don't see the urgency in it?

[00:14:45] Pooja: Yeah, I think that's a really, really good question. And of course, you know, as much as we talk about this in the family history and genetic sense, families are not straightforward, are they, you know, they could be living in various parts of the world, they might not be talking to each other. So many different things can happen in families.

[00:15:02] I suppose the conversations we would usually have would be things, exactly what we've just said, why it's more appropriate to test other family members, because actually you don't want to be revealing something that, um, you know, cause it's their choice to not to find out or to find out. So you kind of don't want to take away another individual's right not to know.

[00:15:22] More often than not, the reason people haven't been tested is because they're not aware. They haven't thought about it in that sense. They haven't really. I've been thinking that actually, if I have a test, it will reveal so and so's result. Usually, when you have those conversations, people are like, Ah, I thought that completely makes sense.

[00:15:38] Why don't I go away and have a conversation with my mom or my dad or whoever the intervening relative is? And often they're open to it. If they're absolutely clear they've been given the choice, They know that this is a possibility, and they do not want a genetic test, then you have to look at the patient themselves.

[00:15:56] Is it relevant for them? How appropriate is it? Are they planning a pregnancy? You know, and you have to think about their own rights at the end of the day, their own autonomy to make that choice. But you try and maintain that family relationship and culture as much as possible before you jump into that step.

Genetic terms revisited

[00:16:13] Irina: Thank you. And, uh, regarding the technical terms, would you be all right to cover Aleles and polygenic risk score, which we've been hearing about, I think, in previous episodes as well. And if I'm not wrong, we've briefly covered cystic fibrosis in the episode with familial hypercholesterolemia. And I don't know if you, Anwar, mentioned then that it is an autosomal recessive disease. And what does that mean? Okay. 

[00:16:38] Pooja: Yeah, so autosomal recessive, uh, genetic condition basically means that you need two copies of your gene to have variants present for the individual to be affected. So all of us have two copies of every single one of our genes. And for conditions that are autosomal dominant, you only need a gene change in one of those copies to, to be at risk of developing that condition.

[00:17:01] Whereas autosomal recessive means that you need two copies. the changes in both of those copies to actually have the condition. So parents of a child who's got cystic fibrosis are likely to be carriers of the condition, which means that they've got one copy of the gene change and the other gene is working, perfectly well. I see. 

[00:17:21] Irina: Thank you for explaining that. 

[00:17:22] Anwar: Were there any others? I think you mentioned polygenic score. Yes. Polygenic 

[00:17:27] Pooja: risk score and alleles. I know we've, we've talked a lot about them in the previous episodes. I dunno whether you want to have a goal at explaining them in simple terms. 

[00:17:35] Anwar: Me? No, I, I don't understand it enough to say

[00:17:39] So I, it's interesting, isn't it, when we don't understand something. We do use jargon, don't we? So, um, I, I'm gonna resort to jargon. So therefore, Puja is giving you, or an expert at putting. complex things in lay language, would you mind having a go? 

[00:17:52] Pooja: Sure. And I think that's one of the things I do. I very rarely use the terms myself because I try to explain it.

[00:17:59] Um, so yeah, so I suppose polygenic risk score, um, the idea is that, that it's a scoring system where multiple genes might have an impact on each other alongside environmental factors that combine together. It's not something that currently is used in clinical practice on a day to day. It's not something that we sort of level, but it's something that we're looking at for certain conditions like in cancer, which is where we heard about it previously, and it's coming in, and it's a lot that's talked about in research, but it's, it's unlikely that you'll be using this term very often in your day to day practice

[00:18:32] and alleles, I suppose, the kind of things we were talking about earlier, um, about the fact that, you know, these gene changes are on two different copies of the gene, it's that we're talking about the copies, the alleles of, of that specific chromosome or that gene that we're talking about now.

[00:18:47] Irina: Thank you very much for that Pooja. 

Pharmacogenomics in Primary Care

[00:18:49] Irina: So we've discussed a lot about genetic testing, the importance of it, the different diseases, but we didn't talk at all about pharmacogenetics, pharmacogenomics. Can we briefly cover that? I'm not a specialist in genomics, from what I've been reading lately and from listening to the episodes. To me, that's the bit of genomics that maybe brings it closer to doing something in primary care and choosing a certain medicine and personalizing treatment for a patient. And I know this has been happening for a while in oncology and other services, but it feels like we're very close to, to actually having a broader use of these tests and, but let's start with what pharmacogenetics is.

[00:19:32] Anwar: Before I do that, I just wonder whether I can chip in first, Pooja, and one is that in primary care, we see 90 percent of the population, means we all in primary care need to be aware of pharmacogenomics. Why? 

[00:19:45] There's potential to improve treatment outcomes. 

[00:19:48] Secondly, enhance patient safety. 

[00:19:52] Thirdly, reduce healthcare costs by not prescribing drugs that are not tolerated.

[00:19:57] And fourthly, to align their practice with evolving standards in personalized medicine. What do we mean by personalized medicine? That really means that the medicines are tailored to the individual rather than giving everybody a simple statin. Yeah. Many of whom will get muscle aches, et cetera. So really what we're saying is integrating pharmacogenomics into primary care is leading to more precise and effective care.

[00:20:23] And as I said earlier, we're the first point of call of patients, and therefore we need to be aware of that. Now, at the moment, as far as, and I'm not a geneticist, I'm still a jobbing GP, but I've heard of tests for, uh, gentamicin sensitivity, for example, which is not very primary care. It's really for neonates, and, uh, what's happened before is people have given the same standards as gentamicin.

[00:20:46] Some neonates get deaf when they've got sepsis and others don't. So what Manchester has done is be able to find out patients that are sensitive to gentamicin and give them a reduced dose. I hear, and again I'm not a pharmacogenomics person, that there are tests that will be coming about sensitivities of statins.

[00:21:04] So, if we find that, then we're not going to be wasting money giving Simvastatin when really we should have gone straight to Rosuva[statin], which is the more expensive version. I think it's only just coming in, so you'll, over the next, I would say, three to five years, more and more of these tests will come. We call them point of care testing, in other words, little spot tests you do in the surgery.

[00:21:26] That's what I think is going to happen in the future, before we start giving up drugs. And also remember If we give up medicines that give side effects, it puts patients off taking medicines of any of that class. So there's also that confidence as well. So I think what I would say from my perspective, it's all going to come into primary care and me mentioning it now is to get you all ready for it.

[00:21:48] Not many applications at the moment, but Pooja, please correct me if I'm wrong. 

[00:21:53] Pooja: No, you're absolutely right. So pharmacogenetics, pharmacogenomics, we often sort of use those terms interchangeably in a way, but the idea really is, is that combined study between pharmacology and genomics and looking at the individual's genomes and kind of working out the changes within that genome that might have an impact on how they respond to certain kinds of treatment.

[00:22:19] So it's kind of stratifying it and making sure it's completely tailored to that patient to avoid those sort of harmful adverse. events for them. Um, and I suppose you're right. It's not something that's, uh, regularly used for everything, but there are a few examples. I keep talking about the National Genomic Test Directory and there are currently four indications where we use, uh, pharmacogenomics.

[00:22:43] So most of them sit within cancer at the moment. So DPYD is an example where, you know, it's, It's commonly, uh, tested for within, uh, sort of gastrointestinal, uh, breast and head and neck cancers. So it's, it's commonly done and it's actually coming into practice. and it's a great example of it. And then of course there's a couple of them, sort of, there's another one in, um, acute lymphoblastic, leukemias again within the cancer setting, but also Mt. Rnr, one for AMG glycosides, which is sort of associated with a mitochondrial DNA mutation. In, in sensory neural deafness. So again, there's a few examples, and these are just very early days, but it's, it's kind of where we're going, and the more we learn about our genome, the more we learn about these variants, and how it impacts treatment, this, this is kind of something that's going to really exactly as Anwar said, you know, this is going to come into primary care, point of care, it's going to be talked about a lot more.

[00:23:41] Irina: Can I ask you something there, Pooja? This is, maybe you already know this, but what's the turnaround for a genetic test? Like, for example, in, um, TBUID, uh, testing, that's for the 5 fluorouracil chemotherapy, isn't it? That's right. So, you, of course, determine the diagnosis of the patient, then you test them to establish if it's, uh, appropriate or not for them to be treated with that, or either if it's going to be more toxic or not, so you dose reduce appropriately.

[00:24:06] In the example with TBUID, The gentamicin effect on babies. Obviously that's more acute scenario. Like it's a baby, he's got an infection. What do you do? Is this a test that happens at birth? Like as part of the heel prick thing, or is it something you have to test then and you get the results ASAP? So you know what you treat with.

[00:24:24] Pooja: Yeah. It's associated with the infection or the particular condition at the time, rather than something that's on heel prick, because it's not familial. It's something that is in response for a treatment, right? And the turnaround time, the question that you asked is within. A few days. It's not, it's not like other genetic testing that you will offer. So I guess there's two differences isn't there? There's this sort of germline genetic testing in families where there's a history of a condition. So you're doing a more sort of broader test looking at. Something that's inherited, whereas these genetic changes are not usually that something that's inherited as such in, in the familial manner, but they are more appropriate for changes within the genome to work out whether they're going to, uh, respond to a certain type of drug.

[00:25:09] So, uh, yeah, the turnaround time is much, much quicker. 

The Generation Study

[00:25:13] Anwar: On a related note, Irina, you've just reminded me of the generation study, where we will be. testing for more than 200 conditions on that heel print. Now that is going to be a game changer and I think, uh, the NHS is trying to recruit about 100, 000 babies for this project.

[00:25:34] It's already begun. I forgot when it began. Uh, you'll probably tell me, but it's going to run until next March. And I personally think that's going to be a real game changer because what we'll be able to do is pick up rare conditions very early. And therefore, the point of picking up early is you put good management plans before disability sets in.

[00:25:59] Pooja: Yeah, absolutely. And it's, it's exactly right. So it's a pilot project that's been run by Genomics England and associated with NHS partners, um, and it's available within certain trusts at the moment, because it is a pilot project until until next year. And the conditions, the way they were picked up. Or agreed upon was exactly that in in cases or in situations where management plans early would actually have a significant impact on their treatment and and how that child or the baby might develop over time.

[00:26:30] So, um, it's not for conditions that wouldn't necessarily have that direct implication or impact, but it's really for those that will be. Yeah, that'll be, it'll be very, very helpful for. 

[00:26:41] Anwar: It's interesting in the, I think it's the last episode, Angela really talked about this sort of early diagnosis is going to prevent that diagnostic odyssey.

[00:26:51] Yeah. Because remember, you know, you know, patients do say, well, why have you gone so many tests over so many years? Because we go through a diagnostic process. But actually if you're then picking up causative genes. Very early, you're going to save costs on unnecessary tests that we've done on that Odyssey.

[00:27:07] So, I think this medicine is going to be totally revitalized, uh, with these advances. So, that's what we all need to know about them. 

[00:27:16] Irina: Thank you both. I think what I'm also hearing from you two and from the previous episodes is that looking at genetic tests is potentially going to become more Something that we all need to get used to, similarly to how we look at a full blood count or UNEs in the sense that we, we would need to understand them and then establish what the best treatment is for that particular patient and choose the medication according to that profile.

Patient Communication and Ethical Considerations

[00:27:41] Irina: Also, one of the other topics that I wanted to touch on from a pharmacy perspective is language. You mentioned Pooja earlier that you don't tend to use all these specialized terms. Is, is. easy to speak to somebody who knows about it, about a defect that happens into a gene. But actually when you're sat in front of the patient, it could become very personal.

[00:28:01] So I think it's really important how you choose the words, how you share the message. And one of the, the other bit that I wanted to get back to, uh, we will, discussing patients and ethical consideration and patient autonomy earlier. How would you go about, so let's say you have a consultation, you have a patient in front of you, you know nothing about their understanding about genetics and genomics.

[00:28:23] How do you make sure you get the best outcome for your patient? How do you share the news? How do you explain this? How do you keep them opened for testing? And if they do say no, what do you do then? 

[00:28:35] Anwar: I wouldn't use the word defects. Defects suggest. Blame. So that's one thing. Uh, I think the other thing, and you really, uh, hit the nail on the head when you talk to cultural bits and where people come from, because I think there are religious and cultural behaviors they've learned from previous generations, and they think, well, that's not for us, that's God's will, etc.

[00:28:58] And absolutely right, they may well be God's will, but the fact that there's a defective gene. I've used the same word, but I'm emphasizing it. Does not, should not mean blame. 

[00:29:10] And a classic one is where people are saying, Well, consanguineous marriages cause more genetic conditions. Actually, that's not the case. It's just the increase of it. There is, but not a massive increase. So we shouldn't be blaming people for marrying cousins. But what we should say, there's an increased risk. and be aware of it. I, so I think there's an issue about information giving and Pooja is an expert on consent, et cetera. But the thing I would be talking about is I'm giving information for them to make a decision.

[00:29:41] And, and genetic counselors will often talk to this non directive approach. Pooja, can I just hand over on that one? Cause that's, that's a very difficult task, isn't it? Cause when patients come to a doctor, they expect an opinion Uh, et cetera. But actually, genetic decisions are so personal. They do need a non directive approach and I've always found it difficult to do.

[00:30:04] Pooja: Yep, you're absolutely right and I think, uh, we certainly get the same questions like you do, you know, but what would you do if you were in my position, day? But it is definitely one of the pillars of genetic counselling. We, you know, in most cases a non directive approach to genetics is crucial because at the end of the day, Yes, we might have an understanding about the gene, we might have an understanding about what it actually means, um, in terms of the management, the treatment, the long term planning.

[00:30:33] But how that fits in with that patient or that family or the culture of the family or that even the timing of testing for that family, we're not experts in that. They are. And I certainly have families that I'll be seeing, you know, over a period of time where at one point they've understood it. They've been open to information.

[00:30:52] But the timing just wasn't right. They've got all these other changes that are going through within their life, and just another little piece of information about genetics that opens up a can of worms for them is going to tip them over the balance. They don't want that information at that point, but they will come in a few years time when they've, Thought about it, process it, work through it, and feel more ready to be able to cope with that information.

[00:31:14] So I guess it's, it's just about being open. And the point that you raised very rightly about language, how do you keep that non directive? It's about presenting information with both sides of the coin. Yes, there is a one in four chance of this condition happening, but there's also a three in four chance that it won't happen, it's keeping all of those options open at each time.

[00:31:38] Anwar: It reminds me of an example of, it was about 21 years ago, where I saw a patient, uh, she had an ultrasound, and that showed thickening of the nuchal fold, and, and I talked about it, probably Downs, and I said, uh, you know, Downs varies, to very severely affected, to mildly affected, and I can't tell you. which one it'll be but that's what it looks like.

[00:32:05] The patient was against termination anyway and she was about I think 12 weeks in and said no I I'd rather she's my child I'd rather be she brought the child into the world. Lovely girl. She's still a patient. I see her quite regularly. Yes, she's got learning difficulties, but she's coping well. She goes to a school.

[00:32:25] She's not working independently, but I felt I couldn't make that decision for her. And she is very happy. She doesn't regret having a child with Down's. I suppose in retrospect, she was lucky not having a severely affected Down's because they vary. And that's the sort of difficulty I have as a doctor is trying to predict. what level of severity, but then it does remind me of a case recently in my part of the world Where there's a three year old with Downs who was seen and mum wasn't aware of a particular detail with Downs patients that there's often immune deficiencies and this patient got chicken pox and then Ended up with a group A strep infection and passed away.

[00:33:15] The mother was told that the lymph nodes that they had will resolve. And I think both the mother and the carers, the medical carers looking after it, didn't appreciate that particular diminished immune response in Down's. And I think that does lead to, and it's a very sad case, but it does lead to the issue about parents learning about the conditions that they're taking. children are suffering from, mainly because I think you can't expect every practitioner in primary care to know all the nuances of Down syndrome, like, you know, immune deficiency, bushfield spots, or whatever it is, uh, about them. But what we do need to do is, um, get the parents and relatives aware of this serious combination.

[00:33:58] I think the genetics department do a great job, but you know, sometimes we need to follow that up with written information. I must say I did do genetics about 38 years ago, 39 years ago, and I used to learn a lot more about patients condition, particularly Huntington's, from the patients. rather than the textbook, which only had a paragraph in it.

[00:34:17] Anyway, Pooja, any thoughts on my ramblings? I'm sorry I rambled on and on, but Not at all. it connected with that patient. 

[00:34:22] Pooja: Yeah, and it's, it's interesting, isn't it, how we reflect on these things as we, as we hear about them and actually think about other cases that kind of fit in. Um, but there are so many different genetic conditions.

[00:34:33] There are so many conditions as a whole that we see day to day. And we absolutely cannot expect that a, Primary care clinician is going to know every detail about every condition at any time that they're going to see the patient. So, yeah, exactly that. You know, we are listening to the parents, we're listening, listening to the family, but also then redirecting and referring, well, you're not quite sure and that's okay.

[00:34:59] You know, get, get them seen by the specialists that, you know, refer to us, refer to the appropriate clinical management teams who will be able to guide a little bit better. Um. And that's absolutely fine, and, and you're right, you know, patients will become experts because they'll know about it, they're living with it every single day, and they're hearing about it, they're living and breathing it every day.

[00:35:19] And it's just listening to those, those things that they come up with, and um, sort of being curious as to why they're thinking about it, where have they read about it, is there any reality within this, and how can we, how can we kind of go on and support them? 

[00:35:34] Irina: Thank you. That's the main message, to always have genetics in mind.

[00:35:38] Okay. And what do we do if you presented all the options to a patient, they've decided to go, say, against testing, do you still have the option? Like if you suspect there's a certain condition and the patient refuses to test, do you still have the option to, you know, go forward on the NHS and, or recommend the other treatment options that are available without having the knowledge?

[00:36:05] Pooja: That's a, that's an excellent question. And I think Yes, absolutely. And I think genetic testing is always a choice, whether it is diagnostic or predictive. It's, it's very unlike other things, really, in healthcare, where it's very much a patient choice as to whether they want to know why they have a genetic condition or why they may be a genetic condition in the family that they might be susceptible to.

[00:36:29] At the end of the day, We still treat the patient and their symptoms and manage them in the way that is appropriate, irrelevant of the genetic test results. If they choose not to have genetic testing, we still need to manage them appropriately based on what we know about them, their own symptoms, but also about their family history.

[00:36:46] So I can think of an example like breast cancer. You know, even if somebody hasn't chosen to have a, a test for a breast cancer gene that might be in the family. There is still a family history of breast cancer. That hasn't gone away. We've still got to offer them screening accordingly. We've still got to think about managing that risk accordingly.

[00:37:04] And that's something we would still be, you know, highly recommending and thinking about that genetic testing is. It's an option and it will, it might take that risk away and it might actually reassure them, but there are certainly some patients who don't want that label and don't, you know, there is still that stigma and kind of going back to that kind of cultural aspects of it.

[00:37:24] You know, people are still afraid of what that might mean. You know, are there going to be implications for them? What do people think about it? What's the society going to think about it? So there's a lot around it, which allows them to think about wider things than just a genetic test. 

[00:37:41] Anwar: It's important that the patients do have the options explained, because I think it's how you explain it and simplify it and not use jargon.

[00:37:52] Because I think for me, and I can think of at least one patient, this is from a long time ago, that were against, I'm talking of Huntington's by the way, which is a piece of research I did 40 years ago, was against it, but when I explained it to them as to why it would help improve their management. They actually took it on board. 

[00:38:10] So sometimes it's about patients not being told or not taking on board the relevant take home message because the options were unclear, jargon. And so therefore, I think, provided the options have been clearly laid out, it's the patient's prerogative. That's, I think, for me, the proviso.

[00:38:31] And it's not always done, uh, well laid out. 

[00:38:35] Pooja: Absolutely. That pros and cons list, isn't it, on each side? Absolutely. 

[00:38:39] Anwar: Absolutely. 

What if there isn't a cure?

[00:38:40] Irina: And I suppose knowing that there's something you can do about it also helps a great deal in making that decision because testing and realizing you have a condition that there's no cure for. I'm not sure it's going to increase your quality of life necessarily, but if you know there's something you can do about it now, there's a treatment available. It could change a patient's choice. Also, 

[00:39:02] Anwar: Irina, even if it's incurable, so I'm thinking of Huntington's where I have a special area of interest. for many years ago. Um, by having a precise diagnosis, you're able to institute management plans for an incurable disease and be proactive and preventive and put care plans in the, for example, adaptation to the house and that sort of stuff. So I, I don't think we should underestimate cure is not always about medical stuff.

[00:39:30] Uh, I think for me, more important than cure is care. 

[00:39:34] Pooja: I see. Thank you. Thanks for explaining that. And actually, with most genetic conditions, the way it stands, there isn't always going to be an immediate cure. management plan in the same way. There isn't going to be a treatment. There isn't going to be a cure.

[00:39:47] There isn't going to be therapy, which is what I think most people are looking for. That's the hope, isn't it? And that's where we're heading. We talk about these examples of pharmacogenomics, et cetera. , there are examples of gene therapy and yes, we're getting there, but that isn't the case for most conditions.

[00:40:01] It's very much about how is it going to impact their day to day? And actually there is a psychological benefit as well. If they're sitting there worrying about it all day, every day anyways. Is this going to help them come through that process a little bit more? 

[00:40:19] Irina: Thank you. 

Conclusion and Final Thoughts

[00:40:20] Irina: Should we wrap up our conversation and try and draw a few conclusions, a few points for people to take home to decide if they need to learn more about genetics, genomics?

[00:40:32] Give me your thoughts. 

[00:40:33] Anwar: I'll start then. So primary care providers should be well versed in genomics because of its increasing relevance to patient care. Personalized medicine, risk assessment, informed decision making, prevention, patient engagement, a holistic approach. So really what I'm saying, as genomics becomes more integrated into everyday health care, It's crucial that primary care providers stay informed to provide the best care possible for their patients.

[00:40:58] Pooja: And I suppose just adding to that, um, you know, thinking about the friendly clinical genetics team that still exists on the other end of it. We're still there and we're very happy to help and answer questions, um, when you get a little bit unstuck with it. So it's not that everything's handed over and, you know, hands up.

[00:41:17] We work together and make things better and improve it for our patients. 

[00:41:23] Irina: Thank you both very much. Thank you for your time. And thank you for agreeing to come on the episode today. It's been really interesting. Thank 

[00:41:30] Munir: And I couldn't agree more. It really has been interesting, so much to learn, and, and Pooja's right. It really is about that, isn't it? It is about working together so that we can improve patient care. And so grateful to Irina for holding the baton and allowing this episode to go forward at a time when, well, I had to be in Barcelona.

[00:41:55] I didn't want to delay the publication of this episode, and Claire, well, she had to be off for something even more important than that, and Irena was able to represent us, and also actually bring her own expertise in terms of a background in pharmacy. Also, thanks to Anwar, and to Pooja, and actually to everybody else who's contributed to this series.

[00:42:15] Really important series. On behalf of the Primary Care UK team, I'd like to thank Shazia for leading this team, and to the North Thames Genomic Medicine Service for sponsoring these six episodes. If there's one thing I'm taking away from all of this, it is that genomics most definitely is relevant for primary care clinicians, so I'm really glad we covered this.

[00:42:35] Next month, we'll move on to something different, but for now, just remember, as Anwar said, when patients come to consult you, think genomics.