Sometimes the question facing people affected by a neuromuscular disease isn't "What kind of test should I have?" but "Should I have a test?"
Finding the correct diagnosis is a straightforward scientific process requiring technological tools and medical detective work (see "Getting the Correct Diagnosis in Neuromuscular Disease"). But like opening Pandora's box, receiving a diagnosis is anything but straightforward. A diagnosis, especially of a genetic disease, can carry an emotional punch that sends patient and far-flung relations reeling.
Now that people can be more easily and exactly tested for specific genetic diseases, the question "Do I want to know?" becomes acute. Below are some common issues confronting individuals and families today.
Q: Is it worth the expense and hassle to undertake new testing to confirm or refute an earlier diagnosis?
A: Yes — and no. In some cases, there are clear advantages to positively confirming your diagnosis; in other cases it won't make any difference at all.
The advantages are found in identifying inheritance patterns, gaining knowledge about the course of the disease and being able to participate in ongoing research.
Different neuromuscular diseases have different inheritance patterns; even within a single disease, such as Charcot-Marie-Tooth disease (CMT), there are genetic variations, says Karen Krajewski, certified genetic counselor and assistant professor of neurology at Wayne State University in Detroit.
If you have a disease with several genetic variations, and if you're hoping to participate in clinical research trials, a precise genetic diagnosis is essential. Knowing the exact mutation allows you to participate in clinical trials aimed at that form of the disease.
Knowing exactly what you have also can be informative when you're planning for parenthood. Rob Roozeboom of Sheldon, Iowa, received a diagnosis of Becker muscular dystrophy (BMD) when he was 5 years old. But in his early 20s — married and hoping to have children — MDA doctors began to suspect he had something else and gave him a DNA blood test for BMD. It came back negative. Based on the test, his disease progression and family history, Roozeboom's diagnosis was changed to limb-girdle muscular dystrophy (LGMD), changing the inheritance pattern for his future children.
BMD is X-linked, meaning all of Roozeboom's daughters would be carriers and would be at risk of having boys with BMD. But Roozeboom's form of LGMD apparently is autosomal recessive, meaning both parents need to be carriers in order for the disease to be manifested in a child. Although all of Roozeboom's children — boys and girls — will be LGMD carriers, the risk of the disease actually showing up in future generations of Roozebooms is less than with BMD.
"Being diagnosed with limb-girdle kind of allowed us to still pursue our dreams of children," Roozeboom says. On Nov. 4, the Roozebooms had a baby boy, Jager, who is doing well.
Even if parenthood isn't an issue, a genetic diagnosis can be useful for other family members. "In families where it's not clear if other people are affected, once you establish a genetic diagnosis, those individuals can be tested so that you know definitely," Krajewski explains.
Another advantage to knowing the genetic diagnosis is that some neuromuscular diseases carry increased risks for other disorders, such as a bad reaction to anesthesia, heart problems or diabetes. An exact diagnosis may help you prevent problems down the line or direct your doctor toward the most appropriate treatment.
But in general, if you have a diagnosis that seems to fit, aren't worried about inheritance patterns and don't plan to participate in a clinical trial, there's no real advantage at this time to confirming a diagnosis by genetic test. In fact, sometimes test results can be vague and ambiguous, leading to more confusion instead of less, Krajewski says.
And some insurance companies balk at paying for the expensive tests, especially if you get more than one. Genetic tests can range from several hundred to several thousand dollars each.
The decision to undergo further testing comes down to personal preference, Krajewski says. "For a lot of patients it [a precise diagnosis] doesn't change things for them. And for others, even though it might not change treatment, there is a feeling of control they get from knowing specifically what's happening, even if they can't do anything about it."
Q: Should children, siblings or other relatives who aren't showing any disease symptoms be tested anyway to see if they're carriers, or might develop the disease later?
A: In general, the medical establishment frowns on testing children for late-onset disease or carrier status if the children aren't showing any disease symptoms and if there's no medical or psychological benefit to knowing at a young age.
"There is no reason for a 6-year-old girl to know about her chances of having a child with a disability — that's her choice to make when she gets older," says Cheryl Scacheri, a senior genetic counselor with GeneDx in Gaithersburg, Md. "You [her parents] might make a different decision when the child becomes sexually active."
But if a family is adamant about testing a child, and they believe a test won't cause any medical or psychosocial harm, then health care providers should "respect the decision," say both the American Society of Human Genetics (ASHG) and American College of Medical Genetics (ACMG). Psychosocial issues include anxiety, negative self-image, uncertainty, social stigma and the impact of knowing on decisions about reproduction, education, career, insurance and lifestyle.
(Click here to see the ASHG/ACMG policy paper, "Ethical, Legal and Psychosocial Implications of Genetic Testing in Children and Adolescents.")
"Fred," feels strongly that his teen-age son — who isn't showing symptoms — shouldn't be tested. Fred, 53, recently learned that he has myotonic muscular dystrophy type 2 and is very concerned about psychosocial issues for his son.
"If he does have it, it probably won't begin to show up until his 40s. I don't want him to be worried at this age, when the disease might not even show up," he explains. "Every girl he thought of marrying he'd have to tell. I don't want to do that to him. I would rather he leads a normal life. If he finds out when he's almost 50, that's different. They may have treatment for it later."
On the other hand, psychosocial issues are the main reason Pete Siegel, 35, of Billings, Mont., wanted his 4-year-old son, Virgil, tested for CMT, although the boy didn't show any symptoms at the time. His son, now 12, tested positive for the disease.
Siegel's father and a few relatives have CMT, but Siegel never was told about it while growing up. He says he battled self-esteem issues because "I couldn't understand why I wasn't as fast and strong as everyone else. I thought it was just me." Siegel believes his father kept quiet about CMT out of fear, denial and maybe a little guilt.
If he'd known, Siegel says, he would have made different career decisions and gone to college. Instead he enlisted in the U.S. Marine Corps and then couldn't make it through boot camp. "I just made some poor choices in my life that if I'd known I had muscular dystrophy, I wouldn't have made."
When a doctor gave him the diagnosis at age 19, he felt betrayed and angry. "I felt they kept a secret from me that affected me. I could have been told when I was 10 or 12."
Siegel is open with Virgil, who already has CMT symptoms. "Whenever he asks questions, I tell him what I know. I don't sugarcoat it. He needs all the information he asks for." An avid hunter, fisherman and stock car racer, Siegel also encourages his son "not to let this be an excuse not to do something."
Lately, Siegel has been urging his sisters to have their children tested because "I see the signs in their legs. It's as plain as black and white. For me, knowledge is power. I believe that in my heart."
Q: What tests are available to see if an unborn child has a neuromuscular disease?
A: We live in a brave new world when it comes to prenatal diagnosis. It's now not only possible to tell if your unborn child has muscular dystrophy, but to ensure from the beginning of the pregnancy that he or she doesn't.
A definite "yes or no" diagnosis can be made via chorionic villus sampling (CVS) at 11 to 12 weeks gestation, or amniocentesis at 15 to 19 weeks. In CVS, cells from the developing placenta are examined; in amniocentesis some of the amniotic fluid surrounding the baby is drawn out and tested. Both tests very slightly increase the risk of miscarriage.
If the fetus is affected, a couple can decide whether to continue the pregnancy, knowing better how to prepare emotionally, financially and domestically for the new child.
With preimplantation genetic diagnosis (PGD), parents can know for sure that their baby doesn't have a particular genetic disease before pregnancy begins. PGD combines the fertility technology of in vitro fertilization with genetic testing.
Eggs are collected from the mother and fertilized in the lab with the father's sperm, and any resulting embryos are tested for the suspected genetic disease when they've grown to the eight-cell stage. Unaffected embryos then are implanted in the mother's womb. Pregnancy success rates range from 20 percent to 50 percent, with younger mothers having the best chances. PGD doesn't guarantee that a baby won't have other birth defects or difficulties.
For obvious reasons, prenatal diagnosis is a white-hot issue among parents and members of the disability community. It involves closely held attitudes toward abortion, the beginning of life, God, fate, disability, social responsibility and the definition of "a good life." Deciding whether to test an unborn child can be agonizing, but it's a couple's personal choice.
Robin Guyton, 39, of Bossier City, La., has a family history of Duchenne muscular dystrophy (DMD), including a 36-year-old brother affected by it. After bearing two daughters (now in their 20s), Robin decided to have amniocentesis with her last two pregnancies — a gut-wrenching but ultimately valuable experience. Her third child, Benjamin (BJ), has DMD but her son Taylor, born in October 2001, doesn't.
"With my first two pregnancies I was young. I didn't worry [about having a child with DMD], and there were no specific tests available anyway," she recounts. While pregnant with BJ she underwent amniocentesis but, after learning the baby was a boy, she decided she didn't want to know the results of the test for DMD.
"I thought, "If he has it, what will I do?" I know it's a horrible disease but my brother has had a productive life. I just couldn't throw away another human being. I went through a hundred different emotions. The lab people looked at me like I was stupid for not wanting to know, but it's a private thing."
But when she got pregnant again with Taylor, she decided she needed to know. "I know how special BJ is," she said. "I just wanted to be prepared in case there was a problem and to prepare the rest of the family. I felt very protective toward the [unborn] child and kind of isolated, like it was just us against the world."
Guyton and her husband, Robert, agreed they wouldn't terminate the pregnancy in case of DMD. The tests came back negative.
Guyton recommends prenatal testing to others with a family history of DMD. "This disease doesn't just affect one person, it affects everybody in the family. You need to prepare people and prepare yourself."
Q: Isn't there a downside to genetic testing? Could the results of a genetic test lead to discrimination by an employer or insurance company?
A: If you already have a documented medical diagnosis of a neuromuscular disease, having a genetic test to confirm the diagnosis won't make you more vulnerable to discrimination. If you have no symptoms and no diagnosis, some safeguards are in place to help protect against possible employment or insurance discrimination based on results of a genetic test.
The first, of course, is the Americans with Disabilities Act (ADA), which prohibits discrimination in employment on the basis of disability. In fact, having a definitive diagnosis can work in your favor, says genetic counselor Karen Krajewski, by documenting that you're covered under the act.
In 2001, the Equal Employment Opportunity Commission (EEOC), which enforces the ADA, shut down an apparent attempt at genetic discrimination by the Burlington Northern Santa Fe Railroad. The railroad was taking blood samples from employees who had filed workmen's compensation claims for carpal tunnel syndrome, allegedly looking for a genetic predisposition toward that disorder. Those who refused to give blood samples were threatened with dismissal. The EEOC ruled that, "Any test which purports to predict future disabilities, whether or not it is accurate, is unlikely to be relevant to the employee's present ability to perform his or her job."
Limited safeguards exist against insurance discrimination. The Health Insurance Portability and Accountability Act of 1996 (HIPAA) says:
Genetic information may not be used to deny or limit coverage in the group (as opposed to individual) insurance market.
Genetic information is excluded from being considered as a preexisting condition.
In certain cases, federal protections against genetic discrimination cover people changing insurance coverage, such as in a divorce or a job change (providing certain standards are met).
Procedures, standards and security technology have been put in place to protect private personal health information, including the results of genetic testing, from being electronically stolen or released without the person's authorization.
Some state insurance laws offer even more protection than HIPAA; check with your state insurance commission to find out. For more information on HIPAA, visit www.cms.hhs.gov/hipaa or call the Centers for Medicare and Medicaid Services (CMS) at (877) 267-2323.
Federal employees were granted some additional safeguards against genetic employment discrimination in 2000, but progress has been slow in protecting the average citizen. Legislation designed to protect the privacy of genetic information and prohibit insurance and employment genetic discrimination has failed several times in Congress in recent years.
Q: Decisions about diagnosis and genetic testing can be really complicated, emotional and have far-reaching consequences. Where can you go for help sorting it all out?
A: That's what genetic counselors are for.
"Because of the tough choices you may encounter with genetic disease, it's good to have someone help you think through the options," genetic counselor Cheryl Scacheri says. "Genetics is a family thing. Physicians don't have as much time as genetic counselors to deal with all the surrounding issues."
A professional genetic counselor takes a detailed family medical history and explains inheritance patterns, reproductive options and the benefits, risks and limitations of testing. While counselors provide emotional support, they don't advocate any particular course of action. The goal of a professional counselor is to facilitate a family's decision making by offering information and outlining options. Most health insurance companies will cover genetic counseling for diagnostic purposes.
"It's best not to just have genetic counseling once," Scacheri advises. "Things change, life issues come up, nieces get pregnant, different things come up over time. It's good to touch base every once in a while."
No matter what you decide about undergoing testing, there's usually a positive benefit to counseling, she notes. "People can feel better about their decisions and not always be questioning what they're doing."
To locate a genetic counselor, ask for a referral from your MDA clinic physician, county medical society or health department, or contact the National Society of Genetic Counselors, at (610) 872-7608 or www.nsgc.org.