Ever since Maya Brown-Zimmerman learned in college that she had tested positive for a gene mutation linked to Marfan syndrome, a potentially life-threatening disorder, she has lobbied other family members to get tested, with mixed results.
Her mother was screened for the FBN1 gene mutation about five years ago, she says, and the result came back negative. Her father’s status will remain uncertain, as he died before he could get tested, says Maya, now age 31 and a board member for the Marfan Foundation. Since she was 8 years old, Maya has been closely monitored for heart problems after a worrisome widening in the aorta — which later returned to normal — led doctors to believe that she might have the connective tissue disorder.
Maya wishes her 29-year-old brother, Matt Brown, would also get tested. But he refuses, despite what she ruefully admits has been an extensive effort on her part. While he hasn’t experienced any heart-related symptoms, she’d like him to rule out the disorder, because changes in the aorta and other areas of the heart can develop without symptoms. “We’ve talked about it over several years,” she says, “and it doesn’t seem productive to keep harping at it, because I don’t want it to damage my relationship with him.”
Inherited mutations like the ones that lead to Marfan syndrome can send ripple effects through an extended family tree and present related challenges, according to researchers and genetic counselors.
After all, a genetic vulnerability plays out among pre-existing family dynamics, including various communication styles, coping approaches, and sometimes relatives who are scattered by distance or past discord. Moreover, even family members who test positive might make different choices about how to act on that information. One sister with a pathogenic, or potentially disease-causing, BRCA mutation (associated with hereditary breast and ovarian cancer) and a houseful of children might opt for ovarian removal, while another who hasn’t yet found the right partner might be angry that her fertility clock has been set on fast-forward. That sort of emotional baggage can certainly weigh down the Thanksgiving table.
Meanwhile, the individuals who start this cascade of notification and related testing can be under enormous pressure themselves, even as they are making their own medical decisions, says Mitchel Pariani, a genetic counselor at the Marfan Syndrome and Aortic Disorders Center at Stanford Hospital. “A lot of times there is concern for the rest of the family,” he says. “Sometimes there’s the fear of having the burden — that they have to be the ones to bring all of this to family members.”
But there are ways to mitigate some of these dynamics, through education and the guidance of clinicians, say Pariani and others. The center at Stanford, for example, provides a letter that the individual can share with family members. The letter describes the condition and related mutation, and provides recommendations about screening or genetic testing. A genetic counselor can work with the individual in advance to brainstorm about ways to notify relatives. The counselor can help clients think about the family’s coping style and potential dynamics, says Heather Douglas, a genetic counselor at Rouge Valley Health System, located near Toronto, Canada.
“There’s no cookie-cutter right way to tell relatives,” Douglas says. “Being prepared and thinking about possible reactions and being considerate are what’s going to help people to tell.”
Degree of Urgency
Marfan syndrome is an autosomal dominant disorder. This means that carrying a disease-causing, or pathogenic, mutation in one of the two copies of the gene is usually sufficient to result in disease. Moreover, a child born to an affected parent has a 50 percent chance of inheriting the mutation from that parent. Autosomal recessive diseases, such as cystic fibrosis or Tay-Sachs, develop only if both copies of the gene harbor a pathogenic mutation. The odds of a child inheriting both mutated genes from two parents, who each carry one, are 25 percent.
Both autosomal dominant and recessive disorders are relatively rare, but the chance of developing the disease if you have one or more pathogenic mutations is very high. Common diseases, such as heart disease and most cancers, do not have a clear pattern of inheritance. They are said to be complex, and the risk of disease in mutation carriers is increased only slightly.
As new people within a family test positive for autosomal dominant disorders, the list of related family members who also must be notified begins to lengthen, Pariani says. One family history sitting on his desk runs nine pages and has more than 100 names.
With Marfan, a genetic heads-up could be lifesaving, Pariani says. The connective tissue disorder can potentially impact many areas of the body, including the eyes, the joints, and the heart — most notably the aorta near the heart, which can gradually widen. If a tear in the aorta develops, it can be fatal. In addition to taking an ARB (angiotensin II receptor blocker) medication, Maya gets regular imaging tests every year to track the aorta’s size. If the vessel becomes too large, a surgeon can replace the area with a graft, Pariani says.
There’s no cookie-cutter right way to tell relatives. Being prepared and thinking about possible reactions and being considerate are what’s going to help people to tell.
Family members are typically more amenable to testing if they’ve seen the death of a loved one from the related disease, because then it’s tangible to them, says Siobhan Dolan, a geneticist and obstetrician/gynecologist at the Albert Einstein College of Medicine and Montefiore Medical Center in the Bronx, New York. That might be especially true if it’s a sudden death, such as from a heart arrhythmia, she says. “They do have that sudden lightning bolt feel about them — your uncle was fine, and then he died.”
Relatives, though, still can break into two camps as they weigh the pros and cons of genetic insights, Douglas says. Some relatives might fear a positive result, but nevertheless prefer to know so they can take any preventive steps, she says. “The other camp is, ‘I don’t want to know about any of this. I don’t want to know if I am a ticking time bomb. I don’t really want to deal with it, and I’m just going to go on like I was before.’”
Maya believes that her brother Matt was initially reluctant to get tested because he might have to curtail his running, weight lifting, and other athletic interests if he has the syndrome. But more recently, she says, cost has become the primary concern.
Matt disagrees that his love of sports has ever presented any major hurdle. “I would much rather get tested and know than go running and have my heart explode,” he says.
But the clinicians he’s spoken with don’t recommend testing, Matt says. Thus, the cost would likely not be covered by insurance and could reach at least several hundred dollars, a stretch on a sportswriter’s salary. “If I could do it very cheaply,” he says, “I would probably do it, even though I don’t think I need it.”
Family Ripple Effects
Douglas, who analyzed in-depth interviews, conducted by her study co-authors, with BRCA mutation carriers about family disclosure, says that sometimes the testing process can knit family members closer together. “There was this idea of being in the club,” when members in an extended family learned that they shared a mutation, says Douglas, who published insights from the interviews in a 2009 study in the Journal of Genetic Counseling. “Sometimes people would meet a long-lost cousin and then strike up a relationship with them that would persist over years.”
In other circumstances, family members can feel excluded, particularly with a mutation like BRCA where there are decisions to be made regarding not just cancer screening but also preventive mastectomy and other surgical options, Douglas says. Such discussions can dominate family gatherings, and even spill over online.
Douglas recounts one situation from her clinical practice in which one family member happily posted about her negative BRCA mutation result on Facebook. Meanwhile, as a relative pointed out to Douglas, another family member connected on the site was fighting ovarian cancer.
Once the testing process begins, no one within the extended family is immune from psychological effects, says Ken Smith, a professor in the Department of Family and Consumer Studies at the University of Utah in Salt Lake City. If a close relative, such as a parent, tests positive for BRCA, then that’s almost a proxy test result for the children, raising their risk of carrying the mutation, says Smith, who researches the social and psychological consequences of genetic testing.
Even a negative result can carry emotional baggage, he says. “There may be survivor guilt issues that can come up if you test negative and they test positive,” he says.
Smith co-authored a 2007 study that looked at family dynamics and functioning among 222 parents for up to a year after they learned their BRCA status. Although the parents did perceive a decline in family functioning after the genetic results were shared, it appeared that other life circumstances outside of the testing process were involved, Smith says.
Every family has its own mix of divorces, money issues, interpersonal conflicts, and other stressors, Smith points out. “Those things can almost take on a bigger role in the light of getting bad news from a genetic test,” he says.
Pariani, at Stanford, tries to counsel his patients that their primary responsibility starts and stops with disclosure. “All they can do is just urge the other individuals to get evaluated and give them the reasons that it will be beneficial. And then it’s up to them.”
That’s the stance that Maya has strived to adopt regarding her brother, whom she credits with being a staunch sibling and supporter of the foundation. She’s got her hands full raising three children, ages 1 to 7 years old, in suburban Cleveland. Her 5-year-old son was diagnosed with Marfan syndrome shortly after birth, and his heart is being monitored, she says.
If Matt develops any chest pain or other heart-related symptoms, he’ll be able to alert the emergency room physician about his family history, she says. As for Matt, if he could find a way to get tested for less than $100, he says he likely would. “Just both to be safe and also, to be honest, to help placate my sister’s concerns a little bit,” he says. “Because I think it bothers her a whole lot more than it bothers me.”