Chapter 2 - Testing Pathway
To ensure decisions to consent or decline genomic testing are fully informed, families must be educated around the potential implications and considerations associated with these tests, alongside the benefits.
These benefits can be both clinical and psychological in nature:
Clinical benefits
Helps with disease identification
Clarifies prognoses and guides management
Provides information on recurrence risks in future pregnancies
Informs reproductive options and decision making > may impact both the patient and extended family
Can help avoid unnecessary renal biopsies and investigations
Assist in identifying healthy living related kidney donors
Psychological benefits
May give certainty in an uncertain setting
Provides options for disease / gene-specific support groups
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Renal genomic testing has benefits from a clinical perspective for both the families and clinicians. A genetic diagnosis may provide information on the genetic kidney condition, including potential associated health problems. It may provide information on prognosis or be used to guide management.
For some parents or patients, this may be important information to understand recurrence risks for future pregnancy planning and the availability of reproductive options to inform their reproductive decision making. This also can be relevant for members of the extended family.
It can often take time for families to attain a specific renal genetic diagnosis, so providing timely access to renal genomic testing can help in identifying the underlying genetic cause, which then helps families to avoid unnecessary renal biopsies and investigations.
Parents of children and adults with kidney disease do face uncertainties associated with having this disease. A genetic diagnosis may provide a degree of certainty and an understanding of why the genetic disease has occurred.
It can also help provide information to link families with condition specific support groups or for some patients and families, knowledge of their genetic kidney disease can inform suitable living related kidney donors who don't have the genetic risk to develop kidney disease.
However, discussing both these benefits and limitations with families can be challenging, as the amount of information parents need can vary.
In thinking about preparing patients and families for decision making about renal genomic testing, it’s really important to discuss both the benefits and limitations of testing. So, as genetic counsellors, we talk to parents about the timing of testing, how much information they need and what is the best time for them to receive that information. It's really about ensuring that patients and parents have enough information to make informed autonomous decisions in a patient centred way. Some patients or parents want to just quickly get information and sign the consent form and move to the next step to ensure that their child gets access to testing and knowledge about the renal genetic condition they're facing, and some people and patients want a lot more information, so we're really guided by the patient in understanding what they need.
Core Considerations
Families need to be informed of the range of possible results or outcomes of genetic testing
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Advice from a KidGen GC:
When speaking to families, I tend to talk about the fact that the test may find the cause of their own condition or their child's kidney condition and provide them with an average percentage pickup rate, and so for both adults and paediatric cases of kidney disease, there's about a 50% combined diagnostic rate for real genomic testing.
I talk about the fact that we may not find an explanation, and even sometimes when we do find an explanation, it may be hard to predict what exactly to expect in the future because it can be variable how kidney disease presents from one individual to the next.
And of course, the possibility of an incidental finding. So in other words, a renal genetic finding that is unexpected in relation to how the disease is presenting.
The other sort of key things that we try to get across as genetic counsellors is the fact that every now and then we do find uncertain results. So variants in a gene associated with kidney disease that don't we don't know the meaning of or whether that variant is contributing to the child or the person's renal condition, or whether it's not contributing.
Really though, with an uncertain result is important for individuals and parents to be aware to reengage with genetic services to ensure that reanalysis of the genetic information is undertaken in the future as knowledge and technology evolves and improves and changes.
The counselling also needs to highlight that genetic findings may have implications not only now, but into the future as well:
I'll explain the result may identify a variant that will tell them information about their or their child’s condition in the future, including the possibility that there could be a progressive condition and some conditions leading to renal failure.
For adults with renal disease, understanding if there is a genetic basis to their kidney disease can help with life planning, understanding if there is a risk of renal failure if they're thinking of planning to have a family in the future, or informing living related kidney donation if a person is going on is in renal failure or going into renal failure.
But the whole idea behind in having this conversation and trying to get the explanation for their kidney problem is to affect management, possibly now for the child or the patient, or into the future.
And the possible implications for the wider family also need to be explained:
Another key part of what we do as genetic counsellors is to think about the potential familial nature of genetic findings. Some conditions have a recessive inheritance pattern, which means that parents could be carriers of the condition, or an x-linked nature of inheritance in a family where a mother may also have a risk of renal disease in the future, as is the case for Alport syndrome, or dominant disease where an individual has one gene affecting their kidney risk and also variable presentation of that kidney disease in an individual and in the family.
So the outcomes of testing can be really important to discuss because it manages expectations and it also links into how the outcomes can help management of the kidney disease and the familial aspects.
So for nephrologists and nurses consenting patients as part of their routine care of a child or an adult with renal disease, these are really the core things and core parts of the conversation to engage with, with your patient.
Once a diagnosis is made with a genetic finding confirming the renal disease, support from your local genetics team is available to give detailed information about the genetic conditions, familial testing and pregnancy planning.
Some families may want to know more information, like how the genetic test results may impact Insurance Policies:
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Advice from a KidGen GC:
On the consent form for genomic testing, there is a section that states that people's ability to get some types of insurance might be affected by the test. And in reality, there are some parents who are concerned about this, but probably for most parents that we see, their main worry is about finding an answer for their child's medical issues and their less concerned about the potential insurance implications when that child's an adult.
For those parents who are concerned and want more information, I think that the main points are that in Australia currently genomic testing cannot affect health insurance. The ability to get some other forms of insurance such as life and income protection insurance, as well as others, are unlikely really to be affected by genomic testing, because that child already has a serious and potential lifelong medical condition and really you’re doing the genomic testing to get an answer for that condition and that medical condition itself will already be taken into account when that child is applying for insurance as an adult.
If parents are really concerned, then obviously I would recommend that they seek independent advice about that and also there are fact sheets that we can provide them from Australian genomics which has information about the current moratorium in Australia of insurance companies using genetic testing as well as the fact sheet from New South Wales genetics.
They may also be concerned about data privacy and want to know more about what happens to their genetic information:
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Advice from a KidGen GC:
When talking to families about data sharing and privacy relating to genomic sequencing, it's important to remember that the processes are laboratories specific in some cases, and so while some of the things we discussed here are general comments, to keep in mind that it can be worth contacting the laboratory you’re using just to check in with them about their processes is so you can inform families accurately.
The way genomic sequencing works is through data sharing essentially, and by that I mean that in order to look at the variants or the spelling of the genes in a particular person’s genetic code, and work out whether any of those variants are disease causing, we actually need to compare the spelling of that person's genetic code, to that of people who don't have a similar phenotype. So when talking to families about this sort of test, usually we mentioned that actually the code that's written out from the person being tested is dropped into a pool of data which is anonymized data of many, many, many people who have had their genomic sequence written out, that we then use in the background as part of our computer processing or laboratory analysis, in order to look at different variants and see which might be unusual in healthy populations, or in people that don't have the same features as a person being tested, so that we can then work out which variants might be of interest for closer analysis. So we need to remember that for families, for most of the laboratories that we do this with (it could be worth checking with your laboratory), but for most laboratories their data will be dropped into that pool so that this test can keep working for other people in future.
Sometimes with genomic sequencing, when we have a variant identified that is of interest, we need to do a little bit more work to resolve the significance of that variant. Is it something that's actually disease causing ie. stopping the gene from working? Or is it benign? Is it normal variation within the population? So in order to do that, it sometimes can be useful to share a person’s information in what we call a re-identifiable way, and what we mean by re identifiable data is to take away the information that's personal to them - their name and their address and that kind of thing - and actually just hone in on the phenotypic information. So what is their phenotype that we can list against a gene variant that we've found that's of interest, and share that information together with other clinicians or scientists around the world who might have an interest in that area or might have had a similar patient presented to them and had the same variant come up, because that can sometimes help us resolve the significance of that variant to know whether it is in fact disease causing or is benign and we need to move on and keep looking for that family’s answer.
Sometimes it can be useful to talk to families about the option of their data being shared in a de-identifiable way, so that we can look towards advancing scientific knowledge generally. So that can be for the purposes of looking further into a particular disease-gene linkage, or other information about a particular variant identified in their family, and that would be with the purpose of just helping science generally, helping other families, and explaining it to them in that sort of way, as opposed to necessarily coming back to this family that's being tested, and telling them something in future. Because of course if we’ve shared share their data in de-identifiable way, usually it's not possible for that information to come back and be re-identified and shared with the original family.
Sometimes when talking about the data sharing and privacy aspects of genomic sequencing, families can come back with questions that aren't the ones you expect, and it could be because they've seen something in a movie or read something online. For example, they’ve heard about ancestry linkage websites and they want to ask you well if you've got my data, does that mean you'll come up and tell me I'm related to all these other people? We've even had some people come and ask, well, if you've got my child’s genomic sequence, does that mean you're going to clone them? Those sorts of questions, although unexpected, should really be dealt with on the fly during the consult, because then you can really reassure families that actually, the laboratories that are doing this testing be it a clinical laboratory or a research laboratory, act under ethical governance, and while that can vary between countries, the fundamental ethical principle remains that samples are used for their intended purpose. So if you have any concerns about a particular laboratory you're using, it could be worthwhile checking in with them and seeing what their specific ethical governance is around data sharing, or the use of samples, so that you can reassure families about any specific questions they have. However, if these questions come up during a consult with families, reassuring that there are ethical principles in place, and that perhaps you're already very familiar with the lab, and you're quite sure about the way they act; or that you're going to look into an answer for those very specific questions for the family, so that they can be reassured.