Is it a Zebra? A Horse? And Does That Even Matter.
"When you hear hoofbeats, think horses, not zebras."
This is not an unfamiliar quote in the medical world. Most symptoms have a common explanation, and it is a useful reminder not to overlook the obvious while searching for something rare.
Lately, I have been wondering whether it lands a little differently when we're talking about hereditary ATTR amyloidosis in the Black community.
Yes, not every ache is amyloidosis. Not all heart disease has a genetic cause. But…
For a few years now, I've heard the same numbers repeated in presentations, publications, and conversations.
“Three to four percent of Black Americans” ....
“One in twenty-five Black Americans of West African descent” …
They're accurate. They matter. So why do they always feel incomplete to me?
Probably because I realized I'd been hearing those numbers without ever stopping to think about what that actually could look like in the real-world.
Three to four percent doesn't feel tangible. One in twenty-five begins to. But neither helped me picture what that actually meant for my people.
Looking Beyond the Percentage
Maybe it's the part of me that spent years working in clinical research, or maybe it's just how my brain works, but I couldn't let it rest.
If roughly one in twenty-five Black Americans carries the V122I variant, what might that represent across the United States?
I wasn't trying to calculate a new prevalence estimate or produce original research. I was simply trying to understand the human scale behind a statistic I had heard countless times.
Then I wondered if someone had already taken that next step. Sure enough, they had.
A 2020 editorial published in the Journal of the American College of Cardiology applied an estimated V122I carrier frequency of 3.2% to U.S. Census data available at the time and estimated that approximately 1.6 million African Americans could be carrying the V122I variant.1
Would that estimate be exactly the same today? Probably not. Populations change, and census data changes with them.
But the exact number isn't what is most relevant to this conversation. The perspective is.
Three to four percent is a prevalence estimate.
One in twenty-five is a frequency.
More than a million people is a community. My community.
That doesn't mean more than a million people have hereditary ATTR amyloidosis, and it certainly doesn't mean everyone who carries the variant will develop disease. We know that's not how genetics works.
What it does mean is that the conversation feels different when you stop thinking in percentages and start thinking about people.
Families. Neighborhoods. Communities.
That's when I realized awareness isn't just about helping people recognize a disease. It's also about helping us understand the impact and scale of the questions that follow.
Awareness Changes the Questions
There's no question we've made remarkable progress.
More healthcare professionals recognize hereditary ATTR amyloidosis than they did a decade ago. More families are learning that when one person is diagnosed, relatives may also choose to undergo genetic testing, and as a result, more people are discovering they carry the V122I variant years before they develop obvious signs of disease.
That's something worth celebrating.
In more instances, the question is no longer, "What is hereditary ATTR amyloidosis?"
For many families, it's, "What does this mean for me?" Will I develop disease? If I do, when?
How will I know whether a symptom is related to hereditary ATTR amyloidosis or something else? What is the real risk to me? What does this mean for my children, my siblings, and my family?
These aren't unusual questions. They're the natural questions that follow when someone learns they carry an inherited genetic variant.
Take BRCA mutation, for example.
A harmful mutation in the BRCA1 or BRCA2 gene increases a person's risk of developing certain cancers, including breast and ovarian cancer. Carrying a BRCA mutation doesn't mean someone has cancer. Decades of research have helped define risk, surveillance, preventive options, and clinical guidance. The genetic test isn't the end of the conversation.
It's where the conversation begins.
For those of us living with the V122I variant, we are navigating a road that is still under construction.
When does disease actually begin? Why do some carriers develop symptoms while others never do? What changes first? How should someone with a positive genetic test be followed over time?
Those aren't just research questions anymore. They're the questions patients and families are asking, often before the appointment is over.
Every awareness campaign has a destination. For years, that destination was diagnosis and effective treatment. Increasingly, it's become genetic testing and earlier awareness.
As a patient advocate, I can't help but wonder whether we've reached another important turning point. As we encourage more people to learn their genetic status, are we equally prepared to support them with the answers they'll naturally seek?
The Conversations Happening Around Our Kitchen Tables
As more Black families learn about the V122I variant, our conversations are changing.
A family member mentions numbness in their hands. Someone remembers an uncle who developed heart failure. Another recalls back surgery, carpal tunnel syndrome, or neuropathy. Before long, someone asks, "Do you think it's connected?"
Sometimes the answer will be yes. Many times, it won't be.
I feel that it is important to acknowledge because most back pain is still back pain, most carpal tunnel syndrome still has other more benign explanations, and most heart disease and neuropathy is unrelated to hereditary ATTR amyloidosis.
At the same time, once a hereditary condition becomes a significant part of your family's story and your community's story, it's only natural to begin looking at familiar experiences through a different lens. You find yourself connecting memories, comparing family histories, and reflecting on stories shared across generations, wondering whether experiences that once seemed unrelated might actually belong in the same conversation.
That isn't alarmism or hysteria. It's how people make sense of new information, especially when it has the potential to affect not only themselves but the people they love for many generations to come.
The challenge is helping families distinguish between what may be meaningful, what is likely coincidental, and what simply isn’t known yet. Awareness should empower people, not overwhelm them. That means pairing awareness with clear, balanced communication about what is known, what remains uncertain, and perhaps most importantly, what is actually actionable.
Research Is More Than the Next Therapeutic Breakthrough
When people hear the words clinical research, many immediately think about a new drug. Those studies deserve every bit of the attention they receive and remain essential to improving care for people living with hereditary ATTR amyloidosis.
The success of therapeutic research has changed the questions we now need research to answer.
Awareness has succeeded in identifying more people earlier in their journey. Research priorities should continue to evolve alongside that progress.
Today, the challenge isn't simply developing effective treatments. It is understanding when treatment should begin, how people with inherited risk should be monitored before treatment is appropriate, which screening tools and biomarkers are most informative during the earliest stages of disease, and how we can identify those most likely to benefit from closer follow-up.
The tests used to monitor hereditary ATTR amyloidosis can be costly, and so can treatment. As more people learn they carry a hereditary ATTR gene mutation, we need evidence that helps guide thoughtful, consistent, and appropriate care. That means understanding who should be screened, when monitoring should begin, how often testing should occur, which findings truly indicate disease rather than normal aging or another common condition, and ultimately who is most likely to benefit from closer observation or earlier intervention.
Those answers are unlikely to come from therapeutic trials alone.
They also depend on natural history studies, patient registries, biomarker research, and other long-term research designed to better understand the years before hereditary ATTR amyloidosis becomes clinically apparent. These studies help identify earlier changes, improve screening approaches, refine biomarkers, strengthen risk assessment, and build the evidence needed to develop clearer and more consistent guidance for monitoring people living with inherited risk.
As awareness grows, conversations about research should extend beyond therapeutic trials to include these types of studies.
People cannot participate in research they don't know is happening or understand the relevance. Many carriers may not realize that these studies are designed to answer many of the same questions they are asking after learning they carry a hereditary ATTR gene mutation.
For many carriers, participating in a registry or natural history study may not result in a new treatment tomorrow. What it can do is help generate the evidence needed to better understand inherited risk, identify the earliest stages of disease, and improve the way people are monitored before treatment becomes necessary.
The therapies available today are the result of research that came before us. The next phase of progress will depend not only on developing new treatments, but also on answering the questions awareness has created.
In many ways, the people living with inherited risk are uniquely positioned to contribute to answering those questions. Their participation can help researchers better understand the earliest stages of disease, generate the evidence needed to refine care, and inform the design of future studies, including the next generation of therapeutic trials.
Sher T, Velarde GP, Gertz MA. V122I transthyretin cardiomyopathy: an opportunity to build trust and resolve disparities. J Am Coll Cardiol. 2020;76(1):98-100. doi:10.1016/j.jacc.2020.04.074.
