What to Tell Your Family if You Have Hereditary ATTR Amyloidosis

Historically, transthyretin amyloidosis (ATTR) has been considered a rare disease. But it affects as many as 4 percent of African Americans and 1 percent of white Americans, making it more common than people think, says Paul Cheng, MD, PhD, a cardiologist and a member of the cardiovascular research institute at Stanford University School of Medicine in California.

ATTR occurs when the protein transthyretin (TTR), which is made in the liver and carries vitamin A and thyroid hormones around your body, breaks down. We all have TTR, but in some people, “this completely normal protein begins to disintegrate and form clumps, which get deposited in various parts of the body — for some reasons that we understand and many that we don’t,” says Prem Soman, MD, PhD, the director of the cardiac amyloidosis center and the Richard S. Caligiuri Endowed Chair in amyloidosis and heart failure at the University of Pittsburgh School of Medicine and UPMC.

Those deposits (called amyloid) can damage organs, typically the heart (called ATTR-CM for cardiomyopathy), the peripheral nervous system (called ATTR-PN for peripheral neuropathy), and some ligaments and tendons. ATTR can happen entirely out of the blue as people age, but hereditary ATTR runs in families due to an inherited gene mutation, says Dr. Soman.

No matter what area of the body is affected, treatment can only stop the disease from progressing — it can’t reverse any damage amyloid deposits have already caused, says Dr. Cheng. Over time, that damage can lead to symptoms like shortness of breath and an irregular heartbeat.

 “The earlier you find out you have the disease, the earlier (doctors) can get you on treatment,” he says.

That’s why it’s important to tell your relatives if you find out you have the genetic version of ATTR. As hard as it may be to break the news, it could help your family members get genetic testing earlier, which could help them identify the disease in the earliest stages.

Here’s how to have this tough but necessary conversation.

First, Know That You’re Doing the Right Thing

If a relative never knows they have ATTR, they may spend years wondering what’s causing their symptoms, or they may even be misdiagnosed with another condition. In fact, this isn’t unusual: Research shows that it takes an average of two to six years for people to be diagnosed with ATTR after their symptoms appear.

ATTR can even be missed by physicians, many of whom may not suspect it right away. “The cardiac form usually presents later in life, so for those who are younger, their physicians may not think of it as one of the possible reasons they have symptoms,” says Cheng. This leads to a longer delay in diagnosis and treatment, allowing the disease to progress further before it’s caught.

“If you can identify the disease early, and if you can intervene and limit organ injury, then people have better quality of life (and) live longer,” says John L. Berk, MD, an associate professor of medicine at Boston University Chobanian and Avedisian School of Medicine and the assistant director of the Amyloidosis Center at Boston Medical Center.

So while sharing the news of your genetic testing and diagnosis may not be the most comfortable of dinner table conversations, it’s worth it. “If you don’t know (you’re at risk for ATTR), you’re unlikely to recognize that the tingling or burning or numbness in your toes is a signal that you should not ignore,” he says.

Talk to All Your First-Degree Relatives

There are more than 140 gene variations that have been linked to ATTR so far, says Dr. Berk.

All these genetic variants are inherited by autosomal dominant transmission, “which means if a person has the gene and has children, about 50 percent of the children are likely to be affected,” says Soman. This also means that half your siblings may have inherited the gene, he says, so “it’s important for people to know about it.”

Talk to all your first-degree relatives about your diagnosis, says Cheng — your parents, siblings, and children — when the timing is right (more on that below).

Be Direct but Empathetic

Exactly how and when you bring up your diagnosis depends on your personal situation and preferences, but it isn’t a conversation you want to have on a whim — say, as your adult child is commuting to work. Think carefully about the best setting for the conversation and the language you want to use.

Start by letting them know you carry a genetic variation that could affect them; then, ask if they want more information, says Berk. This gives them the opportunity to politely decline if they’re not ready. If they say no and your relationship with the family member allows, you could consider a gentle nudge, like, “Being informed empowers people to identify and combat the disease at its earliest phase,” he adds.

If they are open to learning more, reassure them that this knowledge will be helpful, as it opens up options for monitoring and treatment, should they develop symptoms. “None of us likes to hear we might carry gene mutations that carry significant risk, but I think most people want to be in control of their own information,” notes Cheng.

Encourage Them to Seek Genetic Testing

If you’re speaking with adult family members — for example, your siblings — the next step is to encourage them to seek out genetic testing to see if they also carry a gene variation for ATTR. If you have young children, experts generally recommend waiting until they are “old enough to fully comprehend and deal with the implications of a positive result,” says Berk.

The closer your relatives get to the age you were when your symptoms started, the more important it is for them to get screened. That way, their doctor will know if they need to be monitored for symptoms.

Your relatives might also want to consider genetic testing if they’re thinking about having children. “There is the capability to do embryo selection and preimplantation genetic testing to select embryos that do not carry the mutation,” says Berk.

While that choice isn’t comfortable for everyone, some parents find “the peace of mind they get in creating kids who will not have to face the disease and potential lifelong treatments really meaningful.”

Encourage Them to Keep Up With Their Care

Not everyone who carries a mutation develops ATTR — and that’s an important and hopeful reminder to share with family members. “Their first reaction is (often), ‘I’m doomed,’” says Berk. Researchers don’t yet know why some people go on to get sick and others don’t, but right now, there’s no way to tell who will develop symptoms and who won’t.

Sometimes, people are tempted to forgo genetic testing or further monitoring because they don’t think it will happen to them, says Berk. But it’s important to work with a compassionate doctor who takes the time to explain how the disease and treatments work,” he says. “I think it sort of empowers patients,” he says. “It enhances their commitment and compliance with treatments.”

Let Them Know Their Doctors Can Monitor Them for Symptoms

Since people who test positive for ATTR don’t always develop the disease, your relatives may never develop symptoms or complications from it. In that case, you can remind them that their doctors won’t do anything more than genetic sequencing unless any symptoms arise, says Cheng.

If they do go on to experience shortness of breath, an irregular heartbeat, tendon or ligament issues, or other ATTR symptoms, “the physician should always think, ‘Could this be ATTR at play?’ and do the appropriate screening tests,” he adds.

However and whenever you decide to share the news, your goal should be to empower your loved ones. Remind them that you’re speaking up because you care about them and want them to be able to make informed decisions about their health. You’re family — and you’re in this together.

The Takeaway

It may be difficult to talk to your family about hereditary ATTR amyloidosis, but it enables your loved ones to take informed steps to protect their health. Sharing your diagnosis helps family members get genetic testing and early monitoring, speeding up diagnosis and treatment if necessary. The earlier your relatives know they may have ATTR amyloidosis, the better their chances for managing any potential health issues.