Children’s Mercy finds rare genetic diseases in 1,000+ kids

A researcher works in the genetics lab at Children's Mercy Hospital in Kansas City.  The clinic recently announced that it has diagnosed over 1,000 patients, most of them children, with known rare diseases using genetic sequencing.

A researcher works in the genetics lab at Children’s Mercy Hospital in Kansas City. The clinic recently announced that it has diagnosed over 1,000 patients, most of them children, with known rare diseases using genetic sequencing.

Children’s Mercy Kansas City

Children’s Mercy Research Institute is identifying genetic conditions using new technology that could have life changing effects on kids sick with rare diseases and their families, in Kansas City and across the country.

Kelly Ranallo knows better than most the difference this kind of testing can make. About 20 years ago, her second daughter died at just five months old because of a rare medical condition. Genetic technology at the time was unable to diagnose this incurable condition, but she told The Star that having a diagnosis would have shaped her family’s choices during her child’s short life.

“It may not have made a difference on the outcome of her life at the time, but it certainly would have made a difference in how we spent those five months,” she said.

Families like the Ranallos could now get answers about their child’s condition sooner because of the new technology researchers at Children’s Mercy are using to identify rare diseases.

This new technology, called “5-base genomic sequencing,” has helped provide diagnoses for more than 1,000 patients and families in the two and a half years since the research began.

“There are significant outcomes every time you find the answer,” said Dr. Tomi Pastinen, who leads the hospital’s sequencing efforts. Having a diagnosis can open up treatment options, reveal information about family health risks and can lead to connections with others affected by rare diseases.

Pastinen told The Star that other health care organizations across the country are taking note of the advances made here in Kansas City, and are looking to share sequencing data with the Children’s Mercy team to get answers for more families suffering from rare, previously undiagnosed diseases.

The most advanced system in the world

Five and a half years after her devastating loss, Ranallo learned that her older daughter also has a rare genetic condition—different from her younger daughter’s.

Though the family didn’t discover the older daughter’s condition for years, a diagnosis eventually made treatment possible. Her older daughter is now 24 years old.

Ranallo said that experience is not uncommon. As the president of Rare KC, a nonprofit focused on serving those with rare diseases and their families, she has supported many families navigating the diagnosis process.

She added that journeys toward a diagnosis for a rare disease can often take six to eight years of doctor’s appointments, research and dead ends.

But, as the testing technology has improved over time, the process has gotten easier.

Children’s Mercy said this new technology is the “most advanced genomic sequencing system in the world,” and can get patients answers faster and more easily than was ever possible before.

“Today, they would never have (initially) missed her diagnosis,” Ranallo said of her older daughter’s condition.

What kinds of diseases can this help with?

By definition, a rare disease affects fewer than 200,000 people. But there are thousands of different rare diseases that, when combined, affect more than 25 million Americans, according to the National Organization for Rare Diseases.

Among the more common rare diseases Children’s Mercy diagnosed was neurofibromatosis, a condition that causes tumors to form in the brain, spinal cord and nerves. While these tumors are usually non-cancerous, diagnosis is important so that patients can be carefully monitored. The genetics lab has found dozens of cases of this condition in Children’s Mercy patients.

The sequencing also has uncovered singular cases of even rarer diseases like Roifman Syndrome, a condition that causes growth defects and intellectual disability. The NIH estimates that fewer than 1,000 people in the United States have this condition.

So far, researchers at Children’s Mercy have identified around 350 rare diseases in just over 1,000 patients. In some cases, patients received two or even three diagnoses of different conditions based on their genetic sequence.

In an effort to help expand genetic research around the country, the hospital is also launching a first-of-its-kind database of gene sequences linked to unknown medical conditions. It plans to exchange data with other health organizations like the National Institutes of Health (NIH) to help identify the genetic causes of extremely rare illnesses.

Children's Mercy Genetics Lab 2
A researcher works in the genetics lab at Children’s Mercy Hospital in Kansas City. The clinic recently announced that it has diagnosed over 1,000 patients, most of them children, with known rare diseases using genetic sequencing. Children’s Mercy Kansas City

How does this new technology work?

Genetic code is written using four letters: A, C, G and T. This code determines the genes in people’s DNA that control things like hair color, eye color and likelihood to develop certain health conditions. You may remember learning about these letters in biology class.

But there’s a twist: the “C” base can have two variations. The reason why is pretty complicated, but the key takeaway is that these two different types of C’s give scientists five bases to look at rather than the regular four. This makes the sequences more specific, and makes it easier to match patients’ genetic code with known cases of super-rare diseases.

The five-base sequencing technology was developed by a California based company called Pacific Biosciences. Children’s Mercy has been working with the company for around two and a half years, and is among the first hospitals in the nation to apply their science to real patient results.

Can this kind of sequencing cure rare diseases?

Not yet. Genetic sequencing can help scientists identify already known rare diseases in patients, and some of these conditions are treatable using gene therapy or other interventions like surgery or dietary changes.

However, many genetic abnormalities haven’t been classified yet. That’s why Children’s Mercy is working to sequence 30,000 genomes of people with rare or unknown conditions and their families. By sharing this data securely within the medical community, Pastinen hopes that researchers will start to find similarities among patients and begin identifying the genetic causes of unknown illnesses.

“One of our hopes is that this five day sequencing will close that gap between interesting and clinically actionable,” he told The Star. “We want to start to interpret more of the genome… and bring it back into, potentially, medical relevance to the patients and the families.”

Could genetic testing help someone you know?

Both Children’s Mercy and Rare KC are working to get the word out about genetic testing — but a lack of knowledge about rare diseases and the ways sequencing can help identify them has posed a challenge.

“We believe that only a small subset of kids that need genetic evaluation are actually getting it today,” Pastinen said.

Most patients are referred to the program by doctors or specialists after other attempts to identify their conditions have failed. Since many genetic diseases begin presenting symptoms during infancy and childhood, the hospital has focused its sequencing efforts on children — but some adults with lifelong unexplained conditions have enrolled in the program too.

Learn more about requesting an appointment in the hospital’s genetics clinic here.

“Many families suffer from even their providers not believing, necessarily, that there’s something wrong and not getting referred to our specialists here,” Pastinen said. “One of our future goals is to increase access and bring genomic medicine closer to the frontlines, bring it closer to underserved populations and primary care offices.”

He added that outreach to rural hospitals and clinics has been especially important. Children with rare diseases don’t always need to physically visit Children’s Mercy in order to receive this testing — some can simply give a blood sample at their local clinic and have it sent to Kansas City for sequencing.

Ranallo said that her group is working to educate doctors around the country about genetics and making them aware of sequencing options.

“You are never going to be the expert in almost 9,000 identified rare diseases growing every day,” she said her group tells medical students and other healthcare providers. “You just have to be willing to have the humility to say, ‘I don’t know, but let me find you your next step.'”

Do you have more questions about health and wellness in Kansas City? Ask the Service Journalism team at kcq@kcstar.com

Natalie Wallington is a reporter on the Star’s service desk covering government programs, community resources, COVID-19 data and environmental action among other topics. Her journalism work has previously appeared in the Washington Post, Audubon Magazine, Popular Science, VICE News, and elsewhere.

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