Rare genetic disease can strike your family too

When our son was diagnosed in early 2022 with Prader-Willi syndrome (PWS), a rare and serious genetic disease with a frightening prognosis and no cure, my family’s life was immediately turned upside down. Part of the reason the diagnosis was so devastating was that it came completely out of nowhere.

Neither my wife nor I had any known history of genetic disease in our families. If anything, we thought that we had relatively good genetics and an above-average chance of creating a healthy, happy, and generally high-performing child. As a mixed race couple, we also assumed that we’d avoid the many genetic diseases that tend to have higher incidence in more ethnically homogenous populations, such as Tay Sachs disease among Ashkenazi Jews or sickle cell disease in peoples of African descent.

I’ll admit that we were both on the older side when we decided to have our first child—I was 39 and my wife was 38 when our son was born. We were aware that the risk of genetic disease increases with maternal age, but we dutifully took the standard precautions, such as non-invasive prenatal testing (NIPT) and all the usual scans and screens. Despite a few minor aberrations during pregnancy, everything seemed perfectly normal.

So when our son was born with low birth weight, severe muscle weakness, and other signs of a rare genetic disease, the experience was like a tectonic shock that threw us into a complete tailspin. And while we initially thought we were just profoundly unlucky, we quickly learned that our experience was more common than we thought.

Rare diseases are not all that rare

The exact definition of a rare disease varies between countries and regions. In the United States, the FDA classifies a disease as “rare” if fewer than 200,000 people (roughly 1 in 1,650) have it. The European Union, by contrast, sets the cutoff at 1 in 2,500 people. Other parts of the world have different definitions altogether.

Yet no matter how you count, rare diseases are individually rare but collectively common, and while prevalence estimates vary, most research suggests that they afflict hundreds of millions of people around the world. A 2020 study in the European Journal of Human Genetics, for example, calculated that the total global incidence of rare diseases is somewhere between 263 to 446 million people globally, representing 3.5 to 5.9% of the global population. And this was considered a “conservative” estimate.

One challenge in coming up with a precise number is that high-quality rare disease diagnostics are often inaccessible in many places, so the total prevalence of many diseases is often underestimated. Since the majority of rare diseases are genetic in origin, ongoing innovations in DNA sequencing are gradually changing this situation, but it’s still common for many families to toil for years in search of an accurate diagnosis, and for some to never get one at all.

Parents can offset some of the risk with carrier screening services, which help couples determine how likely they are to have a child with a genetic disorder, as well as NIPT, which detects a limited spectrum of conditions in early pregnancy. Newborn screening systems, which are a routine part of neonatal care in most reasonably advanced countries, also support early detection and intervention for a small set of genetic conditions, though most are limited in scope.

More cutting-edge technologies, such as in vitro fertilization and preimplantation genetic testing, may eventually allow us to engineer life and to avoid genetic disease altogether, but these technologies remain far from perfect and are accessible only to a select few. For most of us, becoming a parent involves risks that we are simply unable to avoid.

The long tail of devastation

All in all, more than 10,000 rare diseases have been described in the medical literature. This includes better-known conditions like cystic fibrosis and hemophilia that are at the more prevalent end of the rare disease spectrum, but also a long tail of “ultra-rare” diseases that individually might only impact a handful of people around the world. It also includes a growing number of “N-of-1” conditions that are completely unique.

While some of these conditions are not necessarily debilitating, others are absolutely horrifying in their impact. Some create profound health complications from the moment a child is born, such as severe recessive dystrophic epidermolysis bullosa, a disease that makes a person’s skin extremely fragile and subject to wounding with even the slightest movement or touch, forcing patients to spend most of their life covered in bandages and in constant pain.

Other conditions show no signs or symptoms at birth, but have devastating consequences in early childhood. One example is CLN7 Batten disease, which the rare disease activist Julia Vitarello once described to me as like “raising an outgoing seemingly healthy child only to find yourself a few years later being a round-the-clock caregiver for someone with Alzheimer’s, Parkinson’s, epilepsy and blindness, all at the same time and all in your young child.”

In the case of PWS, the condition that impacts my son, children are typically born with a variety of health complications, as well as a strong predisposition to a wide spectrum of developmental, medical and behavioral challenges later in life. In adolescence, a majority of people with PWS develop “hyperphagia,” or feelings of incessant and unrelenting hunger that are often associated with anxiety and a constant risk of overeating to the point of morbid obesity.

Getting a rare disease diagnosis can be profoundly disempowering, not least because treatments exist for fewer than 5% of these conditions. And even where treatments are available, many of them are extremely expensive, hard to access, and sometimes completely beyond the reach of those without bulletproof insurance or extraordinary personal wealth.

So what can we do to address the burden of rare genetic diseases, or at least mitigate their effects?

Black clouds and silver linings

Despite having spent the last decade working in various healthcare industry roles, I’ll admit that the breadth and scale of the challenge with rare disease caught me by surprise. Like so many industry professionals, my field of vision was limited primarily to the little silos I inhabited, and while I certainly heard about rare diseases, I never spent a lot of time thinking about them.

Yet the more I learned, the more I realized that the rare disease space is among the most vibrant and dynamic segments of the entire healthcare ecosystem, and that emerging innovations in diagnostics, therapeutics, clinical care, and healthcare financing are creating new opportunities to proactively avoid, detect, or treat conditions that were previously intractable and devastating.

Reading about all these innovations, I decided very quickly that I wanted to be part of the community of people that are driving them. Much of my current work is now focused on helping drive improvements in newborn screening and rare disease diagnostics. I’ve also been getting active with the PWS community, which is served by many high-quality patient groups around the world.

If you’re interested in learning more about my personal journey and views on this space, I recently went on Few & Far Between, a podcast hosted by the clinical research firm Biorasi, to discuss my thoughts on rare genetic disease, Prader-Willi syndrome, the power of patient advocacy, and emerging innovations in newborn screening. The full episode is now available at this link, as well as on Apple Podcasts, Spotify, and a few other platforms.

On February 29, representatives from thousands of rare disease communities around the world will be coming together for Rare Disease Day 2024, an annual observance to raise awareness, celebrate progress, and mobilize action for the millions of patients globally with rare, serious and intractable diseases. The zebra is the international symbol of the rare disease community, so you're likely to see a lot of zebra imagery in your social media feeds over the next week.

So if you happen to spot a zebra here on LinkedIn or anywhere else, please take a moment to remember that rare diseases are individually rare but collectively common, impacting hundreds of millions of people around the world. And even if you don't feel any strong connection to this topic today, don't forget that rare diseases can suddenly strike any family, including yours.