Genetic testing: best to know or not to know?

A simple genetic test would tell Emma East if she carries the devastating disease that killed her mother. She's one of a growing number who face this dilemma, reports Kate Hilpern

Facing the future: Emma East at home with her daughter, Olivia (David Sandison)

Suppose, for a moment, that both your mother and grandfather had died of an inevitably fatal neurological disease, and someone offered you a test to see if you were likely to get it, too. If the test showed up positive, you'd live knowing that one day you'd probably die of it, too, possibly as young as your forties. Would you go ahead? Or would you rather not know?

It's a dilemma facing Emma East, a 24-year-old mother of three young children.

And as presymptomatic genetic testing becomes possible for more and more conditions, it's the kind of dilemma that growing numbers of others will also face.

It didn't surprise Emma's mother, nor Emma, when in February 2009 she was diagnosed with Motor Neurone Disease (MND), from which she died nine months later. The disease had already killed Emma's grandfather.

"Although Mum and I knew that most forms of MND aren't inherited, we had this inkling that ours was, and we both worried that one day we'd get it," says Emma.

"So when I recently discovered the genetic developments in MND, I requested an appointment. I just felt that knowing was better than this awful worry. I felt it would enable me to plan better, too, because if my life expectancy could be just 20 years, I'd live very differently.

"For instance, I wouldn't put off going back to university and I'd visit certain places while I still can. I know such news could cause depression for some, but for me, I find it more depressing living on a gut feeling."

But when the appointment came, some doubts crept in. Emma can't be sure, for example, how she would react to the news.

"I can only base it on how I've responded when I've been told bad stuff in the past. Also, it takes two months to get the results and for me, that would be torture."

In addition, Emma wonders if it may be better to be tested in the future when more is known about MND.

"If, 20 years ago, someone was told they'd definitely get breast cancer, it would have felt like a death sentence, but there are many treatments now as a result of growing research. Would it be better to wait a while in the hope that the same happens with MND?"

The biggest thing holding Emma back, though, is that she is not in a long-term relationship. "I think I'd want someone to fall back on on bad days if the test was positive and, if that was the case, to have someone to support me through the disease itself."

While the number of people seeking presymptomatic genetic testing is growing, most people decide not to go ahead. "Genetic information is a one-way street in that, once you know something, you can't 'unknow' it," explains Alastair Kent, director of the Genetic Alliance UK, the charity for people with inherited conditions. "Many, therefore, come to the conclusion that they'd rather not know, at least for now, if they've drawn the short straw of a life-limiting disease."

Although he adds that this is less likely for tests for which the knowledge can be beneficial. "There is a growing subset of cancers, for example, where the treatment you can have is determined by genetics. For example, if you have the gene HER2 for breast cancer, herceptin will work; if you don't have that gene, herceptin can do no end of damage."

Other conditions where people may be more likely to go ahead with the test include some inherited cancers, for which there are preventative measures you can take or for which regular screening could detect the disease early and lead to quicker treatment or even a cure. Then there are people for whom genetic testing helps them decide whether to have children.Others, such as Terry Morris, 44, do it to help their existing children. "Twenty years ago, my sister had a cardiac arrest and was diagnosed with arrhythmogenic right ventricular cardiomyopathy (ARVC), a leading cause of sudden death in people aged under 35," he says. "As cardiomyopathy runs in families, I was offered the test and, for me, it was a no-brainer because if I tested positive, which I did, I could get them tested, which again I did. While my son isn't a gene carrier, my daughter, who is now 15, is. It now means that she can be closely monitored, which could save her life."

If, however, the test simply tells you whether you're likely to get a condition with a poor prognosis, you have to consider how useful that information is, says Kent. "This is why the NHS pre- and post-test counselling is essential." This counselling is non-directive, but helps people explore all the pros and cons for them personally, often over many months. The counselling also aims to ensure that people understand what they're being told, adds Kent.

"People can so easily get the wrong end of the stick with genetics, mistaking chance for probability, for example. Also, with some genetic illnesses, such as tuberous sclerosis, people need to understand that they could get the condition so mildly that they wouldn't even know, or so severely that it could be lethal."

Professor Frances Flinter, genetic consultant at Guy's and St Thomas' Hospital, agrees. "For instance, people often find it hard to understand the difference between absolute risk (their own, individual risk) and relative risk (how their risk compares with other people's). Another area of confusion comes from the fact that there are some genes in which mutations are almost inevitably associated with disease, whereas with others, an abnormality may simply indicate a slightly increased predisposition to developing symptoms."

The implications of genetic testing on family members are also explored in the counselling, she says. "If the person has children who are old enough, we'd certainly encourage them to talk to them before going ahead, because the result may influence their risk, too."

Alison Lashwood, consultant genetic counsellor at Guy's Hospital, says they've had sibling issues, too. "Say three siblings opt for testing and two are positive. The one who gets the good news may experience survivor guilt, while the ones who get the bad news can feel resentful towards the non-carrier of the gene," she explains. Lashwood adds that it can be particularly difficult for pregnant women and expectant fathers who request genetic testing, as it can potentially lead to three bits of bad news, she says – loss of pregnancy, loss of their own health and loss of reproductive freedom. That said, in some cases, a pregnancy can be tested to see if it's an increased risk without revealing the status of the parent with the positive family history.

Lashwood understands Emma East's feeling that an answer, no matter how bad, is better than living with uncertainty. "This is a common response, but what people sometimes experience is that the result can raise a whole new uncertainty, because you may not be able to tell what the first symptoms may be or when they will start."

With Alzheimer's, for instance, is it just everyday forgetfulness or the disease kicking in? Nor is Lashwood convinced that discovering that you're a gene carrier leads to better life planning. "Research has shown that even if people say they will plan their lives differently if they get a positive result, the reality can be quite different. Many carry on as they were."

Professor Kevin Talbot, consultant neurologist and the Oxford MND Centre director, reports that in America, presymptomatic genetic testing has become relatively commonplace, but he still isn't convinced. "If we tested someone with a family history of MND simply for curiosity's sake, the outcome might be that 50 per cent of people would feel reassured, but the other half would be devastated. On balance, we would have done more harm than good, so we tend to discourage this approach."

Of course, the alternative view is that this is paternalistic, and that patients, not doctors, should make the choice about what they should know about their own health, he says. And in the case of some diseases, including MND, there's an option for known gene carriers to participate in large research studies to help pave the way for a brighter future.

"But it's still important to consider if it's better to operate in a world where things are uncertain," says Talbot. "We humans are very good at occupying a space in our heads where things remain positive. Is it really wise to disrupt that by throwing information at people before they're ready?"

Christopher Shaw, professor of neurology and neurogenetics at the Institute of Psychiatry, King's College London, agrees.

"Just because you can get information, doesn't mean you should. In fact, it's only when people are really struggling to get on with their lives that we'd say that curiosity alone is reason enough. Even then, they may not get the clear answers they're looking for."

Among the most definitive and longest standing of presymptomatic genetic tests available is for Huntington's. Back in the late 1980s, when this test first became available, concerns about the implications of relatively young people knowing about a condition they might not get until their forties were enormous, says Lashwood.

"But, in fact, studies have shown that even where people did go ahead and did receive bad news, there tended to be an initial period of anxiety, after which the majority tended to come to terms with the results. That said, research shows that some people still regret the decision they make, even having thought through all the issues."

mndassociation.org; cardiomyopathy.org; hda.org.uk