A decade after becoming the first clinic to offer whole genome sequencing, Children’s Mercy Hospital in Kansas City is pioneering the use of a technology that reveals even more of a person’s genome — called five-base, long-read sequencing.

As its name suggests, this method goes beyond showing just the four DNA bases (A,G,C,T). It also reveals how cells read them and if they are used at all.

“So we have about 10,000 rare genetic diseases, and each of those is characterized by a different problem in the genome,” said Dr. Tomi Pastinen, director of the program Genomic Answers for Kids. “A single letter changed among the 6 billion letters in your genome can lead to a devastating disease and early death, even in the worst case scenario.”

Pastinen led the first clinical study of five-base, long-read sequencing, which was published this month in the Journal of the American Medical Association Pediatrics.

Listen to the full segment via KCUR

PRESS RELEASE: Unlocking Answers Faster. Children’s Mercy Revolutionizes Genetic Disease Diagnosis with a Single-Test

Clinical long-read whole-genome sequencing offers the potential to replace other diagnostic methods for suspected genetic disease, according to a new study from researchers at Children's Mercy Kansas City. 

On Monday, researchers led by Tomi Pastinen published data in JAMA Pediatrics comparing long-read WGS to a basket of other methods, including panels, cytogenetics, microarrays, and exome sequencing. The results are the first to be published since Children's Mercy validated a WGS test based on Pacific Biosciences' HiFi sequencing method. 

The study analyzed 235 cases using long-read WGS and compared those results to 513 historical matched control cases selected on the basis of indication, age, and sex. Their test increased diagnostic yield to approximately 37 percent, compared to 27 percent for all other methods. Time to diagnosis averaged 27 days, compared to 62 days for the other methods, while time to a negative result was 29 days, compared to 91 days.

Read the full article via GenomeWeb Premium

PRESS RELEASE: Unlocking Answers Faster. Children’s Mercy Revolutionizes Genetic Disease Diagnosis with a Single-Test

Genomic Medicine Center at Children's Mercy

Clinicians should prioritize genetic testing for young children who show signs of intellectual disability (ID) or developmental delays, according to a new report from the American Academy of Pediatrics (AAP), a move intended to improve care and outcomes for families.

The clinical report, published in Pediatrics, recommends genome or exome sequencing be used as first-line diagnostic tests in most cases. Chromosome microarray analysis, which looks for genetic differences at a larger scale, is also endorsed as a complementary approach. Together, these tools can identify a wide range of genetic conditions, many of which would otherwise go undiagnosed or be discovered only after years of inconclusive, nongenetic testing.

Pediatricians as Frontline Navigators

Neurodevelopmental disorders — including global developmental delay and ID — affect about 1 in 6 children in the US. But diagnosing these conditions often takes years. The new report aims to speed up that process and ensure clinicians consider comprehensive testing earlier.

Genomic testing can influence medical decisions in a significant number of cases, said Tomi Pastinen, MD, PhD, director of the Center for Pediatric Genomic Medicine at Children’s Mercy Kansas City in Kansas City, Missouri, who was not involved with the report.

“That could be family planning guidance or actual medical management of the child,” Pastinen said.

The new guidance equips pediatricians, often the first point of contact for concerned parents, with a clearer framework for initiating testing, he said.

The AAP identified two paths to diagnosis. First, a phenotype-driven route for children with specific physical or behavioral signs of a known condition. The other is considered “hypothesis-free,” or an agnostic process to use when symptoms are less specific.

Read the full article via Medscape

Children's Mercy Research Institute

Children's Mercy First to Use 5-Base HiFi Genomic Sequencing in the Clinical Setting

At Children's Hospital Colorado, Aurora, Colorado, pediatricians will soon have a new ally in diagnosing and identifying complex neurodevelopmental conditions like epilepsy, attention-deficit/hyperactivity disorder (ADHD), and autism: Genetic testing.

Later this year, primary care clinicians and pediatricians at the health system will be able to initiate genetic testing for children with neurodevelopmental and other disorders directly through the electronic health record system. The goal is to make diagnosing genetic conditions and finding DNA variants more efficient.

“Pediatricians are busy. They are seeing lots of patients. They don’t have a lot of time,” said Scott Demarest, MD, a neurologist and medical director of the Precision Medicine Institute at the facility in Aurora, Colorado. “You have to think about how to make it easy on them, and I think we have the ability from a technology standpoint to start doing that more than we could in the past.”

Demarest and his colleagues in 2023 analyzed data from genetic testing of children with epilepsy at the health system. They found that between 2016 and 2020, the time from when a child first had a seizure to when they underwent testing decreased from 3 years to 8 months. The percentage of tests that successfully identified a genetic cause for their seizures remained roughly stable (11%-13% over the study period) despite a 292% increase in the average number of tests conducted per month. Over 75% of the genetic variants found to cause disease helped inform clinicians on treatment decisions, Demarest said.

Tomi Pastinen, MD, PhD, director of the Center for Pediatric Genomic Medicine at Children’s Mercy Kansas City in Kansas City, Missouri, spearheaded a similar approach in rural communities, providing primary care clinicians with direct access to genomic testing.

Direct-to-provider testing shortened the time to diagnosis by 5.5 months compared with the standard method of first referring patients to a specialist. For instance, genetic testing ordered by a primary care provider showed that the cause of autism and global developmental delay in one patient was caused by a pathogenic variant in a gene, ZNF462, known as Weiss-Kruszka syndrome, a rare condition with a prevalence estimated to be less than one in a million people.

“We’ve found that directly empowering primary care providers to order genetic tests can uncover undiagnosed genetic disorders in these underserved populations,” he said.

Read the full article via Medscape

Children's Mercy Genomic Medicine Center

“Rapid and scalable personalized ASO screening in patient-derived organoids” outlines how the authors were able to create patient-derived induced pluripotent stem cells (iPSCs) and use them to validate personalized treatments in only eight weeks, much faster than the industry average. The paper explains their process, and the team hopes other institutions will adopt their methods to help rare disease patients all over the world get better, faster care.

“We put in every detail,” said Scott T. Younger, PhD, Director, Disease Gene Engineering, Genomic Medicine Center, and leader of The Younger Laboratory. “We even added extra supplementary material. There are no proprietary steps; this needs to be going on everywhere.”

The study’s co-authors are John C. Means, PhD, research scientist, Genomic Medicine Center; Anabel L. Martinez Bengochea, PhD, post-doctoral research scholar, Clinical Pharmacology and Toxicology; Daniel A. Louiselle, MS, research assistant, Genomic Medicine Center; Jacqelyn M. Nemechek, PhD, research scientist, Hematology/Oncology/BMT; John M. Perry, PhD, doctoral research faculty, Hematology/Oncology/BMT; Emily G. Farrow, PhD, CGC, Assistant Clinical Director, Clinical Genetics; Tomi Pastinen, MD, PhD, Division Director, Genomic Medicine Center; and Dr. Younger.

“The ‘bedside-to-bench-to-bedside' application of the patient-derived organoid model system developed by Dr. Younger and his team is an excellent example of how challenges faced by patients, their families and their providers help us prioritize the integration of research with clinical care at Children's Mercy,” said Steve Leeder, PharmD, PhD, CMRI’s Interim Executive Director.

“[The publication] is a really cool opportunity to share the work we’ve done with Genomic Answers for Kids,” said Dr. Younger, whose lab aims to shorten the distance between clinical and functional genomics. “It’s a highly visible journal, so it puts us on the radar of leading the charge on patient-derived rare disease models.”

Driven by personal experience

The article marks not only an important advancement in efficient, patient-specific genomics, but a milestone in a deeply personal quest for its lead author, Dr. Means. His stepson, Trent, is currently a thriving, straight-A junior high student. But when Dr. Means met his now-wife, Chrislyn, Trent was a toddler with an undiagnosed rare condition and brain abnormalities. He was born with encephalocele, a condition that caused some of his brain tissue to be located in his nose.

Fortunately, Trent was successfully treated through surgery, but they still don’t know the genetic causes behind the encephalocele. Dr. Means and Chrislyn were also concerned their younger son, Leuk, could have a rare condition: His fontanelle (soft spot) wasn’t closing, but it healed on its own with time.

When a position at the CMRI Genomic Medicine Center opened up, John and Chrislyn talked about how great it would be to help families like theirs get answers. “I thought it was the best opportunity to somehow make a difference in another kid’s life,” said Dr. Means.

Faster, more efficient answers

Dr. Means joined the Genomic Medicine Center in January 2020 and dove head-first into one of their biggest research challenges: faster and more affordable personalized genomic testing processes.

“We have very diverse rare disease patients,” said Dr. Younger. “We want to be able to do as much as we can for as many people as we can. Scalability is baked into all of our decisions.”

Labs have been generating patient-derived iPSCs for research and personalized medicine applications for almost 20 years. These stem cell lines can be directed down a differentiation path to become organoids, 3-dimensional cell models that replicate patients’ organ development and function. Organoids are particularly helpful when diagnosing conditions that are more prevalent in a certain organ and/or testing organ-specific treatment responses.

But it can be expensive and time-consuming to create patient-derived iPSCs and organoids. Other research organizations charge $5,000 to $10,000 per patient and take between six months and a year to deliver a quality stem cell line and/or organoid...at which point testing can begin.

“Our patients don’t want to wait forever,” said Dr. Means. “My job was to say, ‘How fast and efficient can we make this process?’”

Dr. Means started with the current literature and began combining different proven approaches to build a more robust system. “I spent long and intense hours working on this,” said Dr. Means, “and then, all of a sudden, it clicked.”

The process Dr. Means and his co-authors developed uses only a small number of patient blood cells and significantly lowers both time (around 85% faster) and cost (less than 4% of current market pricing). In addition, the team can process multiple organoids at once, leading to much faster test interventions.

Instead of waiting more than a year for test results, a family could go from blood draw to diagnosis and/or treatment recommendation in a month or two.

Dr. Means is still refining the process and has improved efficiency beyond the current paper’s publication data.

“John really worked hard to optimize the process to a point where iPSC creation only costs about $200 and takes two to three weeks,” said Dr. Younger. “And these turn out to be really high-quality stem cell lines.”

Research with real-time results

With CMRI’s emphasis on translational research, the team's process improvements served a patient-specific purpose. While other labs mostly research with commercially available stem cell lines, the Genomic Medicine Center is able to create lines and organoids for current GA4K patients.

“A major motivation behind the lines we’ve generated thus far is that we believed doing so would provide information,” said Dr. Younger. "We can actually see what happens with the genetic background of actual patients. That’s unlocked amazing opportunities for us.”

In the second part of the paper, the team described a method for faster preclinical testing for three GA4K patients with Duchenne muscular dystrophy (DMD). These patients’ genetic variants were good candidates for treatment with antisense oligonucleotides (ASOs). ASOs are synthetic nucleic acids that bind to RNA in a sequence-specific way to reduce, modify or restore proteins — like dystrophin, the protein DMD patients struggle to produce.

There are already four conditionally FDA-approved ASOs that increase dystrophin production, with others in development. The team wanted to see if they could identify ASOs that could restore dystrophin protein in these patients’ stem cells and/or organoids, which would suggest they could help treat the whole patient.

And they did: Using an ASO matching an approved sequence, the team was able to restore dystrophin protein in one patient’s stem cell line within five days. They also restored dystrophin protein in two siblings’ stem cell lines (as well as contraction rates and calcium levels in their cardiac organoids) with a new ASO designed to target their specific intronic variant.

“We demonstrated the ability to go from patient blood draw to evaluating personalized therapeutics in as little as 6 to 8 weeks — a process that before could take up to a year,” said Dr. Younger. “It gave us confidence we could use these lines and organoids to evaluate therapeutic responses.”

Bedside-to-bench-to-bedside research continues

The close tie between research and clinical efforts at Children’s Mercy leads to much faster practical outcomes than independent labs can produce. As they continue to finetune their process, the team is already helping Children’s Mercy clinicians tailor treatments to patients. They recently tested different seizure medications on a patient-derived brain organoid.

“One of the cool things about working here is that you can actually help some patients in real time,” said Dr. Means. “We were able to narrow down to a therapeutic that worked without the patient having to go through months of trial and error.”

“It’s anecdotal,” said Dr. Younger, “but it feels pretty good. This might be a path forward.”

Dr. Means is currently expanding testing capabilities to be able to do large drug screens with hundreds of patient-derived organoids simultaneously for even more efficient answers. His excitement for precision medicine’s future makes him wonder about the past.

“With my stepson, if we had these capabilities back then, what would we have known?” asked Dr. Means. “What type of help, be it therapy or medicines, could we have given him to have made it a little easier?”

“We got lucky with the surgery being enough for Trent, but we still have unanswered questions,” said Dr. Means. “I figure there are a lot of families out there with the same situation. If you can give some type of answer to a family, they don’t have to wonder if they could have done something more.”

Sharing a blueprint for “something more”

Dr. Younger said researchers all over the world are studying how to deliver that “something more” to rare disease patients. Others are working to overcome the regulatory and cost challenges of designing treatments for one patient at a time. Children’s Mercy just super-charged their efforts with the blueprints for a faster and more efficient patient-specific genomics process.

“Patient-derived organoid models can not only be applied more broadly to create cellular systems for investigating disorders involving the heart, kidney, liver and other tissues, but the approach can also be applied to distinguish between medications likely to work for a given patient and those that may not,” said Dr. Leeder. “Having the capacity to leverage the patient-derived organoid platform at scale uniquely positions Children's Mercy's research enterprise to become ‘bedside-to-bench-to bedside-and beyond’.”

“My vision for the future is that programs like ours would exist everywhere,” said Dr. Younger. “Rare disease is not a centralized problem. At the same time, it’s very clear that our platform is so robust and scalable that people want to start using it now. We’re interested in making as big an impact as we can.”

As a young child in Lisbon, Portugal, Ana Cohen was fascinated by the stories her family shared about their heritage and history. This early interest in family roots, coupled with her passion for science, ultimately led her to the field of genetic diagnostics, where she studies DNA to identify gene mutations that could lead to illness or disease. 

For the past four years, Cohen has served as the assistant director of the genome testing lab at Children’s Mercy Hospital, in Kansas City, where she has focused on providing testing services to underserved communities across the Midwest.

Read the full article via The Kansas City Star

Genomic Medicine at Children's Mercy

Children's Mercy Kansas City has developed and launched its own 13-gene pharmacogenomic panel that it runs in-house, citing easier integration into clinical workflows and a desire to cut down on wait times.

The Missouri-based pediatric hospital system has been conducting PGx testing for years to guide prescribing decisions, primarily within its GOLDILOKs Clinic, where pediatricians and pharmacists meet with patients and families with complex medication needs, such as those who have experienced adverse reactions to medications or who aren't responding to standard treatment. Providers consider various factors, including PGx, to pinpoint the "just right" medication and dose.

PGx describes how mutations in certain genes can affect patients' ability to metabolize medications, information that can help physicians decide which drugs to prescribe. Genetics-guided prescribing ideally identifies drugs patients may want to steer clear of based on the risk of potential side effects and efficacy concerns, without the patient needing to try it out and experience those issues firsthand.

For the decade that Children's Mercy has been running the GOLDILOKs Clinic, PGx testing has been conducted by external labs, until this fall.

Providers at Children's Mercy realized they could gain efficiencies by bringing PGx testing in-house: creating their own genetic testing panel with variants of interest for its patient population, running the tests in the hospital system's own molecular genetics lab to have better control over turnaround time, and integrating genetic results directly into the electronic health record (EHR) system.

The test Children's Mercy launched internally, dubbed Kiddose PGx, "is a targeted genotyping test that we custom-designed," explained Laura Ramsey, co-lead of the Kiddose PGx program and section chief for individualized therapeutics in Children's Mercy's division of clinical pharmacology. Children's Mercy has said it is the first pediatric hospital in Missouri to offer in-house pharmacogenomic testing.

Read the full article via GenomeWeb

PRESS RELEASE: Children's Mercy Kansas City First Pediatric Hospital in Missouri to Develop In-House Genetic Test to Personalize Patient Treatment Plans

Children's Mercy Kansas City Genomic Medicine Center

In this interview with OncoDaily, John Herriges, a specialist in genetics and genomics, shares his insights about the importance of OGM as a comprehensive technique that can detect structural rearrangements throughout the genome while providing detailed information down to the gene level.

What are some of the most significant advancements in genomic testing technologies over the past few years?

In the cancer realm I think that OGM, which has really come to everyone’s attention the last few years, has the potential to be a real gamechanger as it can help streamline testing for patients and can lead to a better genetic classification of tumors.  There are a lot of other testing advances though that are significant, like long read sequencing, tumor methylation profiling, and RNA sequencing.

Read the full blog via OncoDaily

Children's Mercy Kansas City First Pediatric Hospital to Use Optical Genome Mapping in the Clinical Setting

An international team of researchers, including researchers at Children’s Mercy in Kansas City, received a $3.1 million grant to investigate a devastating childhood disease.

Children’s Mercy said researchers will use the money to study a deadly childhood disease, leukodystrophy.

It’s a rare genetic disorder that affects 1 in 5,000 children. Doctors say it causes progressive loss of neurological function.

Dr. Tomi Pastinen said the grant will extend genomic tools developed at Children’s Mercy to understand the unsolved leukodystrophies.

He said there are more than 60 forms of Leukodystrophy. Some can be treated – many more have experimental therapies available.

See the full story via Fox 4

PRESS RELEASE: Children's Mercy Kansas City, University of Utah and RI-MUHC Researchers Receive Nearly $3.1M Grant to Study Deadly Childhood Disease

More than 50 types of Leukodystrophy have been identified, which can cause a range of symptoms including seizures and intellectual impairment. Swift diagnosis and intervention are critical as most children diagnosed with Leukodystrophy die before their teenage years.

The research aims to address the diagnostic challenges by leveraging advanced genome sequencing technologies spearheaded by the Genomic Answers for Kids program (GA4K) at Children’s Mercy.

“We are using long-read genome sequencing (HiFi-GS) to uncover genetic variants that are not detectable with standard short-read sequencing to increase the diagnostic rate for complex cases,” said Tomi Pastinen, MD, PhD., Director, Genomic Medicine Center, Children’s Mercy and the Contract Principal Investigator (PI) of the study. “Collaborating with the other PIs, Dr. Josh Bonkowsky from the University of Utah and Dr. Geneviève Bernard from the RI-MUHC on this research underscores our global commitment to addressing rare disease in hopes of accelerating the delivery of crucial interventions and providing answers to families sooner.”

Co-investigators include Scott Younger, PhD, and Isabelle Thiffault, PhD, both of the Genomic Medicine Center at Children’s Mercy.

Dr. Pastinen will take the stage at this year’s RARE Advocacy Summit to share more on this research along with other GA4K updates, “Genomic Answers for Kids is leading the way in diagnosing kids with rare disease with over 8,000 children and total of 15,300 family members involved. We are excited to share this is the fourth NIH grant supporting the program to date,” Dr. Pastinen said.

CMRI collaborated with Salina Pediatric Care, a rural clinic in Salina, Kansas, for a one-year pilot project. Salina is located 175 miles from Children’s Mercy Kansas City. The pilot study, which ran from July 2022 to June 2023, found more than double the historic rate for rare disease diagnosis among the rural population and also cut the time-to-diagnosis by about five months. The pilot project for rural expansion was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health.

Read the full article via Global Genes

Children's Mercy Kansas City Research Institute

Genomic Answers for Kids

Children's Mercy is the first healthcare system to use this world's most advanced genomic sequencing technology in the clinical setting to accelerate diagnoses for even more patients and families.

The cutting-edge technology replaces rapid exome, chromosomal microarray analysis, and other conventional diagnostic testing as a first-line assessment for the most critically ill patients in the hospital with a strong suspicion of genetic disease.

"We are excited about this collaboration that signifies a significant step forward in leveraging cutting-edge technology to further genomic research and clinical care," said Emily Farrow, PhD, CGC, FACMG, Assistant Clinical Director, Clinical Genetics, Children's Mercy Kansas City. Geneyx Analysis will play a crucial role in enhancing our ability to analyze and interpret long read genomic data, ultimately leading to advancements in pediatric healthcare."

"We are thrilled to partner with Children's Mercy in their mission to improve pediatric healthcare through genomic training, research and analysis" said David Yizhar, CEO at Geneyx Inc. "This collaboration highlights the growing importance of innovative technologies in driving progress in the field of genomics."

"We are encouraged to see Geneyx and Children's Mercy Kansas City leverage the foundational HiFi sequencing benefits of higher accuracy and longer reads," said Christian Henry, President and Chief Executive Officer of PacBio. "Geneyx, a PacBio Compatible Partner, brings informatics solutions to accelerate genomic understanding, which may ultimately offer insights to Children's Mercy clinicians to better impact rare pediatric diseases."

Children's Mercy is providing a 4-day short course on next generation sequencing and analysis on June 10-13. The course features hands-on workshop analysis, including long read HiFi sequencing data. In-person and virtual attendance options are available.  

By Donna Pitman

Alli Kisner had the best pregnancy.

She and her husband, Ben, were ready to be parents, even if that was a few weeks early.

“We had the twins at 34 weeks. They spent ten days in the NICU. Then, we had two healthy babies heading home.” Hudson and Hailee, were dreams come true and the couple couldn’t ask for more.

A year and a half after they were born, they got something they never would have asked for: A rare disease diagnosis for Hailee.

“We realized she was aspirating,” Alli recalls.

They spent ten days at Children’s Mercy Hospital where Hailee was tested for geneticabnormalities. That’s when they discovered she has Trisomy 9P, a partial duplication of the ninth chromosome. Only 149 other people in the world have been diagnosed with the condition.

See the full story via KMBC 9

Children's Mercy Kansas City Research Institute

Genomic Answers for Kids

Children's Mercy Kansas City First to Use 5-Base HiFi Genomic Sequencing in the Clinical Setting

Like a lot of sectors, the biopharma industry kicked off a tumultuous year with a number of shakeups. Big and small biotech companies alike saw thousands of layoffs, not to mention significant leadership changes.

But 2023 also saw a number of technological advancements hit some major milestones, not to mention some big changes in how investors are approaching the sector. “There's gonna be a lot of building this year,” Vijay Pande, a general partner at Andreessen Horowitz had predicted to Forbes in January — and he wasn’t wrong.

Whole Genome Sequencing Enters The Clinic

Since the Human Genome Project was completed in 2003, there have been significant advances in genome sequencing, making it better, faster and more useful. To get the speed required for applications like diagnostics, sequencers would chop DNA up into tiny bits so they could be quickly “read” and put in order. This produced powerful advances but limited how much information researchers and doctors could obtain about a person’s genes.

That’s recently changed with the advent of what’s called “whole genome” sequencing, which allows DNA to be cut in larger chunks in ways that make it easier for sequencing machines to put them back together in the right order. This technology enables an understanding of the structure of a person’s DNA, which provides a better understanding of how those genes actually work in a person’s body.

In 2023, whole genome sequencing made some strides out of research labs and public health applications and into actual clinical practice. Earlier this month, Orchid, a startup backed by 23andMe Cofounder Anne Wojcicki and Coinbase CEO Brian Armstrong, announced that its whole genome sequencing of embryos is now available in IVF clinics. These reports enable prospective parents to screen embryos for genetic risks and improve the chance of having a viable pregnancy.

And in October, Kansas City-based Children’s Mercy Hospital announced it was putting its whole genome sequencers, manufactured by PacBio, into clinical practice. This will enable the hospital to accelerate its ability to diagnose genetic diseases in its patients, Tomi Pastinen, the hospital’s genomic medicine director, told Forbes. He added that he also hopes that his hospital’s decision will inspire others to do the same. “We hope that clinical adoption is the catalyst to really open the floodgates for these types of genome sequencing,” he added.

Read the full article via Forbes

Children's Mercy Kansas City First to Use 5-Base HiFi Genomic Sequencing in the Clinical Setting

Children's Mercy Kansas City Research Institute

Genomic Answers for Kids

By Rebecca Gannon

It's a breakthrough for a rare disease diagnosis, and it has wide-reaching impacts on children from Canada to Puerto Rico and beyond. And it's all because of the Children's Mercy Research Institute in Kansas City.

The work in the Children's Mercy Research Institute lab is more than vials and samples. It is hope and answers.

"The Genomic Medicine Center at Children's Mercy has been doing cutting-edge genomic diagnostics in children for over ten years," explained its director, Dr. Tomi Pastinen. "In the last four years, we've adopted the most advanced genomic sequencing technology, first in the world for diagnosis of children with rare diseases," he continued.

See the full story via KMBC 9

Children's Mercy Kansas City First to Use 5-Base HiFi Genomic Sequencing in the Clinical Setting

Children's Mercy Kansas City Research Institute

Genomic Answers for Kids

She talked with Dr. Tomi Pastinen and his team in the Children's Mercy Genomic Medicine Center.

Watch the full story via NBC News

Children's Mercy Kansas City First to Use 5-Base HiFi Genomic Sequencing in the Clinical Setting

Children's Mercy Kansas City Research Institute

Children's Mercy Kansas City Genomic Medicine Center

By Mark Johnson

The landmark deciphering of the human genome more than two decades ago allowed doctors to solve thousands of medicine’s cruelest mysteries, including the reason 10-year-old Celia Steele has never walked or talked, and now needs tubes to deliver oxygen and food. Deep in the genetic blueprint of the Wichita girl, doctors discovered the cause: two mutations in PDE2A, one of the 20,000 genes in the body. Just four people in the world share her condition.

The answer mattered deeply, but it came with disappointment. Doctors have yet to find a treatment. As powerful and transformative as the sequencing of the human genome has been, the medical revolution it kick-started still falls short, often delivering explanations for illness but no solution.

But hope for Celia and millions of other people with hereditary diseases rose on Wednesday with the announcement of a second scientific landmark: a new, more detailed version of our genetic code that finally begins to account for human diversity — a factor of critical importance to medicine.

Read the full story via The Washington Post

Children's Mercy Kansas City Research Institute

Genomic Answers for Kids at Children's Mercy

Four-year-old Maddie loves cheese and fruit snack gummies, being right in the middle of the action, and playing with her twin sister, Kellie, and older brother, Colin. When she was diagnosed with Angelman syndrome, it changed the course of her family’s life forever, setting them on the path to help launch the area’s first Angelman Syndrome Clinic at Children’s Mercy.  

“She is the happiest kid you’ll probably ever meet,” said her dad, Patrick Sargent. “The smiles she exudes is what gives everybody their energy to get through a lot of the hard stuff.”  

 What is Angelman Syndrome? 

Named after the physician who discovered the disorder, Angelman syndrome is a rare genetic disorder caused by a mutation in the UBE3A gene on the 15^th chromosome. Children with Angelman syndrome are known for their generally positive demeanors. They also have developmental delays, trouble with movement and balance, and speech impairments. Many experience seizures and a wide range of other symptoms and complications.  

“Maddie is nonverbal, but she’s incredibly communicative,” said her mom, Laura Sargent. “Her physical development has been really impacted by where her deletion is. We were told she likely wouldn’t walk. She walked! She’s starting to climb stairs.”   

After her diagnosis at Children’s Mercy in January 2020, Maddie’s family went to Chicago and Boston to seek out Angelman syndrome specialists. Over the years, they’ve developed “an army of caretakers.” Laura, a pediatric nurse practitioner who formerly worked at Children’s Mercy, has been instrumental in seeking out the best treatment for Maddie and navigating the insurance labyrinth.  

“Having a background in health care has been immensely helpful,” said Laura. Maddie currently attends a therapeutic pre-school five days a week; has physical, speech and occupational therapy three days a week; aquatic therapy twice a week; and one-on-one Applied Behavior Analysis (ABA) therapy in-home. Despite being happy with the specialist care they were receiving out-of-state, they were longing for expert help closer to home.  

“Maddie was hospitalized at Children’s Mercy in July of 2021,” Laura said. “While we had these wonderful specialists in Denver and Boston that could be a phone call away, they weren’t in the hospital. When Maddie needs emergent care, I can’t pick her up and take her to Boston. I can’t take her to Denver. I needed somebody at Children’s Mercy.” 

Patrick agreed, adding that even getting to regular annual appointments was challenging enough.  

“It’s not easy to travel with special needs kids, especially when you’re taking a 3+ hour flight or 8+ hour drive,” Patrick said. “Logistically, it’s tough.”  

The Sargents began meeting other Angelman families in the area and found many didn’t have the resources to travel to specialists or were struggling with the insurance process. “In some cases, their kids just weren’t getting care, and that’s heartbreaking,” said Patrick.  

The Sargents wanted more for Maddie, and they wanted more for her peers in the area. So they decided to do something about it: explore starting an Angelman Syndrome Clinic at Children’s Mercy. 

 Collaborating for Better Care 

The Sargents started a nonprofit, Maddie’s Mission, and held a block-party fundraiser. They met with Diane and Terry Gallagher, whose daughter, Elizabeth, also had Angelman syndrome, to discuss their shared passion for supporting care and research. They talked to their contacts at the Angelman Syndrome Foundation.  

Meanwhile, the Children’s Mercy Enterprise Program Management Office (EPMO) was doing its own research, confirming the need for an Angelman syndrome clinic in the area. There was indeed a big gap in coverage: families with the means were traveling all day to get to specialty clinics; families without were making do. Children’s Mercy was already on a path to creating a solution and philanthropic support could accelerate making it happen….a win-win situation!     

Gifts from the Sargents, Maddie’s Mission, the Gallaghers, and the Angelman Syndrome Foundation created funds, including one that is endowed, to support a new Angelman Syndrome Clinic and Angelman syndrome research efforts. (If Angelman syndrome is cured in the future, the funds will shift to support other neurology and rare disease needs.)  

“The passion of the Sargent Family has been extremely moving. The impact their caring philanthropy will have on patients and families visiting the Angelman Syndrome Clinic and seeking research-based answers is astounding,” said Kate Migneron, Director, Philanthropic Giving. “In addition to the funds for the clinic, having an endowed fund means it will live at Children’s Mercy forever and says we’re going to have this care here for the long run. That means a lot to patients and their families.” 

 “A True Partnership” 

J.B. Le Pichon, MD, PhD, FAAP, Professor of Neurology, has made collaboration a priority in his career, working with Nigerian physicians on research and partnering with community physicians and families to bring epilepsy care to rural areas of Kansas through Project REACT.  

“I’m really interested in these types of partnerships where it’s not purely physician driven,” said Dr. Le Pichon. “There is a true commitment, and everybody’s involved.”  

Based on families’ needs, The Angelman Syndrome Clinic at Children’s Mercy is designed to be a medical home for area patients and a hub for innovative new research on the disease.  

“A medical home is where all of the child’s needs are addressed,” said Dr. Le Pichon. “You see the child as a whole. That’s really important for children with Angelman syndrome because their needs are so broad.” 

The monthly, half-day clinic is based in Neurology and hosts 17 patients already. Every patient is seen by Dr. Le Pichon, and the clinic coordinates visits to participating subspecialties (Genetics, Nutrition, Gastroenterology, Orthopedics, Speech and Language Pathology, Developmental and Behavioral Health, and Physical and Occupational Therapy) according to each child’s needs.  

“Every child who enters the clinic will be offered the option of participating in a research study,” said Dr. Le Pichon. In addition to Children’s Mercy Research Institute’s Genomic Answers for Kids study and an effort to study Angelman syndrome’s phenotype expression based on genotype, Dr. Le Pichon has identified several therapeutic studies that he and the clinic’s Patient Family Advisory Council will review for potential integration.   

“Parents are going to have a real say in terms of what [research we pursue],” said Dr. Le Pichon. “I'll be presenting to them, and then we’ll be making the decision together.” 

 Hope for the Future 

Other institutions are conducting promising research on Angelman syndrome, and the Children’s Mercy Research Institute is eager to join the effort.  

“I think we have the potential to become a center of excellence for Angelman syndrome,” said Dr. Le Pichon, agreeing. “In order for that to happen, we are planning to develop some solid research through the CMRI.” 

Patrick echoed them, saying that there is hope for a cure one day. “Access to research is a game-changer not just for us, but for families in Omaha, Des Moines, Arkansas, all of Kansas, all of Missouri.” 

Being able to participate in innovative studies is just one aspect of the well-rounded care the clinic provides. Young people with Angelman syndrome now have a home at Children’s Mercy, where they can get expert, holistic, consistent care. “And be home for dinner right after your appointment!” Patrick said.   

“I hope that all the kids that have Angelman syndrome in the region have access to the same level of care that Maddie has,” said Laura. “We would love everyone to have equal access.”  

Angelman Syndrome Clinic at Children's Mercy

After striking a record speed earlier this year, nanopore sequencing continues to make headway in the realm of rapid genetic testing, with a new preprint study led by University of Washington researchers demonstrating that the technology can help elucidate a newborn's genetic risk for a specific disorder in as little as three hours after birth.

The study's ultra-rapid turnaround time, which is the fruition of optimized sequencing workflow and targeted data analysis, marks somewhat of a new advancement for nanopore sequencing in terms of speed. However, researchers still face a journey to harness the case-specific breakthrough into broader clinical applications and routine genetic disease diagnostics.

"The initiative of the study is basically [to explore] can we use sequencing to help us with clinical decision-making more rapidly?" said Danny Miller, a pediatrics geneticist at the University of Washington and the lead investigator of the preprint paper, which is currently available on MedRxiv.

This study "demonstrates the power of the nanopore technology and its capability of producing data fast and allowing the scientific team to monitor the production in real-time, which sets the nanopore technology apart from some of its competitions," said Tomi Pastinen, director of the Genomic Medicine Center at Children's Mercy Kansas City. "To my knowledge, [nanopore sequencing] is the only genome-wide technology that could be applied so rapidly to achieve that kind of high-confidence genotyping."

While Pastinen's group has not yet moved into the newborn sequencing space, his team is known for conducting long-read sequencing on the Pacific Biosciences platform to help solve rare disease cases through the Genomic Answers for Kids (GA4K) project.

Based on the results presented in the paper, Pastinen said it was clear that the early sequencing data would not have allowed researchers to carry out genome-wide interpretation. However, he said for the specific application scenario described in the study, which is effectively confirmatory sequencing for two genetic variants, nanopore sequencing, with its advantage of moving fast, is "completely appropriate."

Read the full article via Medscape

Genomic Medicine Center at Children's Mercy

Children's Mercy Research Institute

“This is a major shift in contemporary clinical gene testing by next-generation sequencing, which continues to rely on the genetic code that was first described in 1961. The technology allows us to see into part of the human genome that has never been clinically tested and interpret changes beyond genetic code,” said Tomi Pastinen, MD, PhD., Director, Genomic Medicine Center, Children’s Mercy Kansas City. “On average, only 30-40% of rare disease cases are diagnosed. What we are doing is giving those remaining 60% of families hope that we’ll find answers by discovering relevant gene variations in long-read sequencing only detectable by using this technology.”

Thanks to $18.5 million in philanthropic funding, Dr. Pastinen started the Genomic Answers for Kids (GA4K) program at Children’s Mercy, a first-of-its-kind pediatric data repository. The goal is to collect genomic data and health information for 30,000 children and their families over seven years to create a database of 100,000 genomes.

Just three years after launching the program, GA4K has already hit a major milestone providing 1,000 rare disease diagnoses to families, far out-pacing other rare disease diagnostic programs. Of those, Dr. Pastinen and his team successfully sequenced nearly 300 genome samples using the cutting-edge 5-base sequencing, which captures all genomic variants in a single test allowing for one-stop assessment of patient DNA instead of sequential testing by multiple clinical tests and laboratories.

“What once was a previously undiagnosed disease-causing mutation in a rare disease case is now discoverable because of full 5-base genome sequencing,” noted Dr. Pastinen.

In addition, each analyzed genome harbored a number of rare functional variations unique to each patient expanding the “genome alphabet” available to study for unsolved rare disease. This data has been recently published and is available for preprint.

“Children’s Mercy is once again moving the goalpost and pushing the envelope for what is possible for discovery through advanced genetic sequencing,” said Tom Curran, PhD, FRS, Senior Vice President, Executive Director and Chief Scientific Officer. “We are years ahead in this space and have been driven by the realization that clinical sequencing as it was being done today was not sufficient, so we set out to advance the science in hopes of moving kids to the forefront of research discoveries much sooner.”

Because of the advancements Children’s Mercy has made in Genomics, other health care organizations and undiagnosed disease clinics across the country are collaborating with Dr. Pastinen and his team to solve difficult cases through long-read data and 5-base sequencing.  

“It is a major challenge to understand why many children with genetic conditions remain undiagnosed despite all the advances so far in genetics and genomics. Hassenfeld Children’s Hospital at NYU Langone’s collaboration with Children’s Mercy allows us to use the latest long-read sequencing technologies to help families find answers,” says Gilad D. Evrony, MD, PhD, from Hassenfeld Children’s Hospital and the Center for Human Genetics and Genomics at NYU Langone Health.

This new advancement in technology and genome science allows Dr. Pastinen and his team to reach optimal results in a single test giving families hope everywhere.

“Patients and families living with rare disorders often wait decades to find an accurate diagnosis. Many of us enduring a heart-breaking journey despite current genetic testing options,” said Kelly Ranallo, Founder, RareKC. “The hope that 5-base sequencing offers our families is truly transformative to children not only here in the Kansas City region but across the globe. We are incredibly grateful to Children’s Mercy, our philanthropic community and the unwavering commitment to push the boundaries to ensure every child and family has a future of hope.”

Thank you to our lead philanthropic Genomic Answers For Kids donors:

Black & Veatch Corporation

Brad Bradley and Roberta Harding

DeBruce Foundation

Linda and Paul DeBruce

Dee and Dave Dillon

Marion Merrell Dow Donor Advisory Fund

The Stanley H. Durwood Foundation

Robert and Marlese Gourley

Members of the Hall Family in Honor of Adele Hall

William T. Kemper Foundation - Commerce Bank, Trustee

Krueger Family Foundation

Learn more about Genomic Answers for Kids.

By KCTV 5 Staff

Someone riding a bicycle from the Golden Gate Bridge to the Statue of Liberty is a rare thing.

Jörg Richter, a 62-year-old man from Germany and former firefighter, is doing just that in an effort to raise money and awareness for Care-for-Rare America.

Care-for-Rare America is a charity that help children suffering from rare diseases.

KCTV5 Photojournalist Rob Rhodes caught up with him as he rolled up to the Children’s Mercy Research Institute.

See the full story via KCTV 5

Children's Mercy Research Institute

Children's Mercy Genomic Medicine Center

U.S. News Live Presents…

Webinar: Will Genetics and Genomics Deliver Precision Health?

In this webinar, leading experts discuss the latest on how widespread genetic screening programs can be incorporated into routine care, allowing patients to identify future risks and to develop more effective personalized approaches to treat disease or even to ward it off entirely.

Speakers include Dr. Tomi Pastinen, Director of the Genomic Medicine Center at the Children's Mercy Research Institute.

Dr. Carol Saunders is the division director of the Clinical Genetics and Genomics Laboratory (CGGL) at Children’s Mercy Kansas City and clinical director of the Genomic Medical Center at Children’s Mercy Research Institute (CMRI), where she is currently focused on clinical testing and research specifically on discovering rare disease gene associations. Dr. Isabelle Thiffault is assistant director of molecular genetics in the CGGL and director of translational genetics at CMRI. She works closely with Saunders on genome sequencing testing. Together, Saunders’ and Thiffault’s team averages at least 10 to 15 publications a year focused on gene associations, with hopes of finding similar gene associations across global publications.

How long have you worked in the field of genomics and what brought you to the genome center at Children’s Mercy?

Saunders: I came to Children’s Mercy in 2002 right out of fellowship training in clinical molecular genetics, to direct the Molecular Genetics Laboratory. As was typical at the time, we specialized in single gene testing, meaning one or a few genes at a time. In 2011, Children’s Mercy made the decision to invest in genomic medicine and brought in three researchers to launch a big multi-gene panel using next-generation sequencing (NGS.) These researchers had brilliant technical knowledge but needed a clinical laboratory director to guide the design of both the laboratory space and testing process, so they sort of “inherited” me. Together we built the first pediatric genome center — what is now the Genomic Medicine Center at Children’s Mercy Research Institute. That multi-gene panel was offered as a broad symptom-driven test for rare pediatric diseases and was followed by clinical genome and exome sequencing. Since we were such early adopters of this technology, we have a vast amount of data, which has translated into a lot of interesting observations about phenotypic expansion, genotype-phenotype correlations, and new gene-disease associations. This has fueled my research.

Thiffault: I am from Montreal, Canada. I studied and trained mostly at McGill University. I have a master’s degree in cancer genetics, a Ph.D. in molecular genetics, and a post-doc in translational medicine. After postdoc, I decided to apply to the Molecular Genetics Fellowship Program or CCMG (Canadian College of Medical Genetics) program, which is the equivalent of the ABMGG (American College of Medical Genetics Genomics). Both programs are comparable and recognized — CCMG/ABMGG trainees can take Canadian and/or American board exams without additional training. During my fellowship, I read an academic paper by Saunders and the Children’s Mercy team and it grabbed my attention. I emailed Dr. Carol Saunders, who at the time was leading this research, to see if I could do an “elective CCMG rotation” at Children’s Mercy to learn about “50-hour differential diagnosis by whole-genome sequencing.” She kindly replied that they were too busy, but they needed to hire – and I might be a good fit. I started the position in March 2014; the first months were “credited” as a an elective CCMG rotation and I took the ABMGG board exam in 2015. It was a win-win!

Read the full article via Clinical Leader

Genomic Medicine Center at Children's Mercy

Children's Mercy Research Institute

Celia spent years seeing doctors without getting answers as to why she was different. She is nonverbal, suffers from seizures, has low muscle tone and cannot walk. As the years passed, Cruz-Steele says they began to feel isolated and started to lose hope.

In 2019, that hope was restored with a phone call from Children’s Mercy Hospital’s Genomic Answers for Kids program. They were able to match characteristics Celia has to other people through a sort of database or repository of patients with unexplained symptoms.

“We were able to find out that she has these mutations that were just recently described to cause the kind of disease that she has," said Dr. Tomi Pastinen, the program’s director.

The team at Genomic Answers for Kids discovered Celia has PDE2A. She’s one of only five people in the world known to have the condition and the only one in the United States.

By Carl Zimmer

Two decades after the draft sequence of the human genome was unveiled to great fanfare, a team of 99 scientists has finally deciphered the entire thing. They have filled in vast gaps and corrected a long list of errors in previous versions, giving us a new view of our DNA.

The Human Genome Project was an audacious undertaking, given how much there was to sequence. Scientists knew that the twin strands of DNA in our cells contained roughly three billion pairs of letters — a text long enough to fill hundreds of books.

Researchers were left to put them together like the pieces of a vast jigsaw puzzle. To assemble the puzzle, they looked for fragments with identical ends, meaning that they came from overlapping portions of the genome. It took years for them to gradually assemble the sequenced fragments into larger swaths.

All told, the scientists added or fixed more than 200 million base pairs in the reference genome. They can now say with confidence that the human genome measures 3.05 billion base pairs long.

Within those new sequences of DNA, the scientists discovered more than 2,000 new genes. Most appear to be disabled by mutations, but 115 of them look as if they can produce proteins — the function of which scientists may need years to figure out. The consortium now estimates that the human genome contains 19,969 protein-coding genes.

With a complete genome finally assembled, the researchers could take a better look at the variation in DNA from one person to the next. 

“It’s a great advance for the field,” said Dr. Midhat Farooqui, the director of molecular oncology at Children’s Mercy, a hospital in Kansas City, Mo., who was not involved in the project.

Dr. Farooqi has started using the genome for his research into rare childhood diseases, aligning DNA from his patients against the newly filled gaps to search for mutations.

Read the full article via The New York Times

Learn more about our Genomic Medicine Center

Children’s Mercy Kansas City is proud to announce that Dr. Tomi Pastinen, director of the Genomic Medicine Center at the Children’s Mercy Research Institute, was recognized by Modern Healthcare as one of this year’s Top 25 Innovators. Dr. Pastinen also holds the Dee Lyons/Missouri Endowed Chair in Pediatric Genomic Medicine. This year’s Top 25 Innovators championed solutions to reshape the industry in big and small ways, pushing boundaries to help solve healthcare’s greatest challenges.

"There’s never been a more urgent time for the industry to experiment with innovations that can reshape how care is delivered. The members of this year’s class of Top 25 Innovators have introduced ideas that engage consumers in new ways, lower healthcare costs and take unique approaches to managing population health. The honorees were selected for their work in one of four areas: consumerism, cost reduction, population health and quality/safety. They were selected from nearly 200 nominations. We congratulate this class of honorees and look forward to following their careers," said Aurora Aguilar, editor of Modern Healthcare.

“Rare disease patients, particularly children with rare diseases, are being left behind when it comes to receiving a diagnosis. Dr. Tomi Pastinen and his team of researchers launched Genomic Answers for Kids to bring genomics into the core of rare disease research taking place at Children’s Mercy. This first-of-its kind pediatric data repository has the goal of collecting genomic data and health information from 30,000 children and their families,” said Paul Kempinski, MS, FACHE, president and CEO of Children’s Mercy. “We are hopeful to soon witness truly comprehensive access to genetic testing – with optimized interpretation of these tests – to provide a full picture of rare disease and enable precise, sustainable development of therapeutic strategies in the future.”

The complete ranking is featured in the August 16 issue of Modern Healthcare magazine.

See profiles of the honorees

Learn more about the Genomic Medicine Center at Children's Mercy

A special virtual event marked the official opening of the new Children's Mercy Research Institute.

The institute's new nine-story building on Hospital Hill in Kansas City is where physicians, scientists, and others will work to find answers to pediatric medicine's most challenging questions.

Twenty-year-old Ben Soden is a living testament to the work being done at Children’s Mercy’s Research Institute.

Four years ago, sitting in the school lunchroom, Soden knew something was wrong.

"I could feel my heart just pounding out of nowhere. I hadn't done any exercise," he said.

After discovering his heart rate was just as elevated when he was sleeping, Soden’s mom took him to Children’s Mercy. The team in the Genome Center discovered something a general blood draw wouldn’t have picked up: Soden has differences in his DNA which make it difficult for him to metabolize certain medications at a normal speed.

See the full story via KMBC

Learn more about the Genomic Medicine Center at Children's Mercy 

What would you do if your six month old baby had a seizure, and no one knew why?

“He almost kind of unlearned everything. He couldn’t use the utensil. He couldn’t sit up on his own,” says Elizabeth Hilton, Patrick’s mom.

A terrifying thing for brand new parents Elizabeth Hilton and Justin Cartmell.

So they took their six-month-old baby Patrick to Children’s Mercy in Kansas City hoping for some answers.

It wasn’t until close to a year later that they learned Patrick was born with DeSanto Shinawi Syndrome.

A rare genetic disorder that causes developmental delay, intellectual disability, behavioral problems, feeding difficulty, and seizures.

“it was a relief when we got the diagnosis. But there’s definitely been it’s challenges for sure,” says Cartmell. “The learning curves, those are pretty tough. Trying to see… you do things repetitively and don’t get any results. It’s a little hard to take from time to time. But, whenever those results show up, nothing else can replace it.”

Patrick is three now, and is doing pretty well.

Read the full story via KOAM

Learn more about Genetic Research at Children's Mercy 

Children's Mercy Hospital helped solve a mystery a family in Bolivar, Missouri, had lived with for years.

"It's just like living in the dark. You don't know what's happening, where you're going to go. No future. It's hard to have a plan," said Kaden Isenberger, 18.

"You know something is wrong with your child but you can't explain it," said Casie Isenberger, Kaden's mother.

Labs showed kidney, liver and heart issues. But there was no diagnosis, except for the certainly that something was wrong and rare.

"Unfortunately, only about 30% of those families know the cause of their disease in their kid," said Dr. Tomi Pastinen.

Enter Children's Mercy's Genomic Answers for Kids. It sort of like a data depot for rare diseases.

"We're collecting higher depth of genetic data than any project to date in the world, actually from these rare disease families, and to help the global research community and rare disease community reporting this data available to other researchers," Pastinen said.

Kaden and his brother, Ty, found theirs in MFN2, which is a condition that affects fat storage. They're two of five people in the United States who have been diagnosed.

"There is light even if we don't get the medicine. We know what to do in order to help ourselves," Kaden Isenberger said.

Read the full story via KMBC 9

Learn more about Genomic Answers for Kids

Today it was announced that Genomic Answers for Kids, a first-of-its-kind pediatric data repository and the flagship research initiative of CMRI, has received $16 million in donations to accelerate the search for diagnoses and novel treatments for pediatric genetic conditions.

Pediatric research is significantly underfunded as the National Institutes of Health allocates only 10% of its $37 billion research budget to pediatrics and currently only about 20% of kids with rare or life-threatening diseases get an answer from genetic testing. Tomi Pastinen, MD, PhD, director of the Genomic Medicine Center, said this project will improve those outcomes. “On average, families wait five to seven years for a diagnosis and that’s simply too long – this database will be used to identify other genetic diseases, and research treatments and cures in the future. It will move kids to the front of the line.”

The goal of Genomic Answers for Kids is to collect genomic data and health information for 30,000 children and their families, creating a database of nearly 100,000 genomes.

“Normally to get a project of this magnitude up and running it would take years, but because of this $16 million dollar gift, we already have more than 1,750 families enrolled in the program, which has resulted in more than 6,000 new genomic analyses, more than 170 genetic diagnoses with new answers found every week, and contributed to the discovery of eight new genes,” Dr. Pastinen said “We’re investing in thousands of families here in the Kansas City region and beyond to give families the answers they deserve.”

Thanks to 76 donors to-date, Children’s Mercy already has more participants enrolled in Genomic Answers for Kids than other studies across the nation that have been in progress for several years.

“I’m continuously amazed at the generosity of the Kansas City community – it is a community that believes in rallying together to give hope and healing to families for generations to come. Because of these donors, Children’s Mercy and Kansas City will be a destination not only for kids in our region, but around the world – what an incredible gift!” Jenea Oliver, Senior Vice President and Chief Development Officer, said.

Brad Bradley and Robbie Harding are one of the donor couples. Robbie’s daughter was born with Down Syndrome and at the age of 12 was diagnosed with Acute Lymphoblastic Leukemia and had to undergo 30 months of treatment. Two years later, she relapsed and had to endure an additional 30 months of treatment. She has now been cancer free for over three years, but it was a long journey.

“Like most parents with children that have been diagnosed with a rare disease, I’ve asked myself many times ― why does this happen? Is there a treatment? If so, is there a less painful, damaging treatment? And in our case, why do kids with Down Syndrome have ten times the risk of getting cancer?” Brad said, “We give to Genomic Answers for Kids because learning the answers to some of these baffling questions will hopefully bring some comfort and even normalcy into what is a very dark and difficult time for many families.”

Learn more about Genomic Answers for Kids.

Thank you to the following lead donors for their support of Genomic Answers for Kids and the Children’s Mercy Research Institute:

American Century Investments Foundation

Big Slick

Vicki and David Block

Roberta D. Harding and William F. Bradley, Jr.

DeBruce Foundation

Linda and Paul DeBruce

Dee and Dave Dillon

The Stanley H. Durwood Foundation

Diane and Terrence Gallagher

Members of the Hall Family in honor of Adele Hall

Dr. D. Stanley and Sidney Hite

William T. Kemper Foundation – Commerce Bank, Trustee

Bill and Becky Krueger

Marion Merrell Dow Donor Advisory Fund

Virginia Merrill

Harry Portman Charitable Trust

R and C Charitable Foundation

Jim and Mary Stilley

Erika and Kevin Sweeney

Looking at the angelic face of 4-year-old Emerson Schrivener, you’d never suspect anything was wrong.

Emerson’s mom, Destiny Moser, said Emerson is one of roughly 500 children in the world diagnosed with Niemann Pick Type C, a generic condition that, according to doctors at Children’s Mercy Hospital, could resemble Alzheimer’s Disease or dementia. 

This family is one of many that’s excited to see the Chidren’s Mercy Research Institute expanding.

Dr. Tomi Pastinen, director of Children’s Mercy’s Genome Center, said his group employs hundreds of researchers who are hungry for methods of getting kids into treatments that can help them.

“There is definitely hope,” Pastinen said. “I think we have to think of rare diseases collectively. Most of them are unsolved. The grand prize for us is to give answers to those over two thirds of families who don't have answers today.”

“Our hope is that with research and science, we'll meet her where she's at, and it will be there before it's too late for Emerson,” Moser said.

See the full story via Fox 4

Learn more about the Children's Mercy Research Institute

Learn more about Genomic Answers for Kids at Children's Mercy

By Lily Lieberman

Children's Mercy is providing Kansas City families with something that can't be measured: answers.

"We're slowly starting to release results for families that have, on average, waited five to seven years for a diagnosis," said Tomi Pastinen, director of the Center for Pediatric Genomic Medicine.

The Children's Research Institute of Children's Mercy is in the early stages of building a first-of-its-kind pediatric data repository to facilitate the search for answers and novel treatments for pediatric genetic conditions.

Pastinen said the goal is to collect genomic data and health information for 30,000 children and their families over the next seven years, creating a database of nearly 100,000 genomes.

One in 10 Americans live with a rare disease, and 50% of those are children. Only 5% of rare diseases have a Food and Drug Administration-approved treatment, and thousands of genetic diseases affecting children remain undiscovered and untreatable.

Read the full story via the Kansas City Business Journal

Learn more about the Genomic Medicine Center at Children's Mercy

Every baby born in the United States is given a routine blood test to screen for dozens of inherited medical conditions. Now, the U.S. National Institutes of Health is exploring whether to use DNA sequencing to screen newborn babies for additional genetic abnormalities and disorders. Such DNA testing would likely complement, but not replace, the current routine blood tests.

However, before routine genetic screening of infants even approaches reality, many questions need answers, including whether genetic sequencing can accurately identify babies who will develop a disease, according to Dr. Joseph A. Bocchini Jr., chairman of the Advisory Committee on Heritable Disorders in Newborns and Children.

More clarity is also needed on issues surrounding newborn DNA testing, including consent, accessibility, data privacy and the potential changes to medical practice and costs.

Read the full story via CNN

Learn more about Genomic Medicine at Children's Mercy

Rare diseases are individually very rare, but collectively they're not rare at all, with one in 10 children diagnosed with a rare disease. New disease-gene assertions are being made at a stunning rate, with around 40 new genes discovered each month. This work is possible through genomic sequencing, where the DNA code is read for each patient and checked for variants, which are akin to spelling mistakes.

Many of these new disease-gene assertions are through the identification of de novo variants, which means the variant is not present in either parent. Such variants are interesting because they rarely occur and often tend to be pathogenic. However, if they are found in a new gene not yet associated with human disease, additional patients and other evidence is needed to assert a gene-disease relationship.

Researchers at Children’s Mercy studied 21 new de novo variants in genes of unknown significance. We spoke with Carol Saunders, PhD, Clinical Director (pictured right), and Isabelle Thiffault, PhD, Director of Translational Genetics, at the Genomic Medicine Center (pictured left), about how this research could lead to better understanding of rare diseases.

What prompted you to conduct the study?

Dr. Saunders: We had a growing list of patients with interesting variants in new genes that had insufficient evidence linking them to disease in humans. This means we didn’t have enough data to classify the variant as pathogenic and we couldn’t just call it benign. Without further evidence, these patients and families are left without a diagnosis.

In hopes of finding answers, we shared information on patients with de novo variants in 21 new genes with researchers around the world to find more such cases. It takes more than one patient to establish a gene-disease relationship - more evidence and more replicates are needed to make genetic diagnosis.

Why are these genes significant?

Dr. Thiffault: The problem is trying to prove that they are significant—we don’t always know. Many of these conditions are so rare that only a couple of people worldwide have the same particular disease—the aim is to find them!

Why is it important to collaborate with your peers around the world?

Dr. Saunders: One way we find additional patients with variants in our gene of interest is through an online matchmaking service that connects us to other researchers with similar patients. Sometimes it takes a while to get a match with a patient that a variant in the same gene, but it’s these collaborations that lead to publishing new gene-disease associations and will ultimately give us the confidence to say this is diagnostic for a particular patient. We have ongoing research collaborations with colleagues in Italy, Netherlands, Canada, Australia, France, Belgium and the UK.

Knowing that a gene is associated with a certain condition helps us understand the biology of humans, which may eventually lead to treatment or a cure.

How do you decide if a gene is linked to a disease?

Dr. Thiffault: As part of our study, we used a new scoring tool to assess the level of evidence for each gene-disease association. This incorporates case-level genetic data, functional studies, animal models which all together helps us determine if there’s strong enough evidence for a gene-disease association. Having enough well-phenotyped patients with variants in a gene of interest is a necessary part of this—you can’t just rely on animal modeling.

We’re the first to publish this exercise for curating new genes with de novo variants identified through clinical testing, which we hope becomes the new model. We really view it as a community service and if everybody would share their case level data and variant curation, researchers and clinical labs would have so much more information and be able to provide accurate reporting for patients with rare disease.

We intend to repeat this exercise with a whole new list of ~100 genes. These findings not only provide patients with answers, but allows families to network with others affected by the same new genes.

Do other organizations share their data?

Dr. Saunders: Some do and some don’t. We are one of a handful of clinical laboratories that share the interpretation of every clinically curated variant from our laboratory with a database called ClinVar, which other laboratories can freely access to see our interpretation. We get questions every week from people around the world trying to interpret variants in their own patients, and this exchange of information is extremely useful. If our interpretation disagrees with another lab, we work to resolve the issue. We find out what data we each have and how we came to the conclusion, so we can get the right data out there.

What is bench-to-bedside research and why is it important?

Dr. Saunders: Bench-to-bedside research is when results from our lab are directly used to develop new ways to treat patients in our hospital.

We’ve identified numerous treatable conditions in the lab. In some cases it's identifying a vitamin a child may be missing which can be absolutely life-saving. This would not be possible if we didn't have the kind of tools we have in our lab. These capabilities will continue to grow as we adopt new tools that can look at different types of variants in the genome. Translating that into clinical testing and what that means for patients is really important. We’re helping change the course of people’s lives for the better.

What is your hope for the next 10 years?

Dr. Thiffault: We have a limited understanding of the genome right now. Even though we can sequence the whole genome for the most part, we’re only looking at two percent of gene sequences. There's about 8,000 genetic diseases, yet we don’t know what genes go with half of these cases and within each gene there's thousands of potential variances.

I hope we really have a good understanding of the rest of the genome we don’t understand to be able to provide answers to more patients and families.

What is the biggest takeaway for parents?

Dr. Saunders: I want parents to know the rate of new disease gene discovery is astonishing and just because they don’t have an answer now, doesn’t mean it’s the end of the road. New genes and new information will lead to better understanding of rare diseases.

Over the course of our year-long study, at least half of the genes moved from limited evidence to strong or moderate evidence, which led to a diagnosis. So, it’s important to reevaluate things every year if you don't have any answers yet. We’re always working on new research and new testing that will be meaningful for our patients and their families.

Read the full study On the verge of diagnosis: Detection, reporting, and investigation of de novo variants in novel genes identified by clinical sequencing.

Learn more about The Center for Pediatric Genomic Medicine at Children’s Mercy.

By Kelly Ranallo, Founder/President, Turner Syndrome Global Alliance and Founder of RareKC

The National Institutes of Health recently launched the All of Us Research Program, a historic effort to gather data from one million (or more) people living in the United States. The goal is to accelerate research by using data from the program to learn more about how individual differences in lifestyle, environment and biological makeup can influence a person’s overall health. This tailored approach, which is commonly referred to as “precision medicine,” is key to preventing and treating diseases, and I’ve witnessed firsthand the impact it can have on a person.

My Daughter’s Story

In 2008, our oldest daughter Allie, who was eight years old at the time, was diagnosed with Turner Syndrome.

Turner Syndrome is a rare genetic condition that affects one in 2000 females, in which a female will lose part or all of her second “X” chromosome during fetal development. Symptoms include short stature, delayed puberty, infertility, heart defects and certain learning disabilities.

After the diagnosis, Allie underwent several surgeries and multiple rounds of anesthesia during a sixth month span. For unknown reasons, she didn’t respond well to the anesthesia and pain management wasn’t working. It seemed as if the over-the-counter medications worked better than the prescriptions meds. No one knew why this was the case, and her care providers (myself included) started to doubt her when she said the pain medications weren’t working.

Allie started hormone replacement therapy two years later. Once again, she complained of the horrible side effects from the medication. At this point, I knew we needed to do something since she would need treatment throughout her lifetime. That’s when we were referred to Children’s Mercy to undergo genetic testing to understand how Allie was metabolizing drugs.

Genetic Testing Changed Everything

What we found out changed everything. We learned Allie’s body does indeed metabolize drugs differently than most kids. You can only imagine how I felt as a mom after doubting her all those years. Armed with her genetic results, her medical team was able to adjust her medication and prescribe the correct dose that would work for her. It also enabled her doctors to make more informed decisions regarding other medications and empowered Allie to know when something wasn’t working, which was especially important when she went off to college in 2016.

We Are All Rare

Since Allie’s genetic results were strangely odd, we were asked to enroll in a research project that would some day help other children and families benefit from precision medicine. We jumped at the chance to give back and it quickly became apparent to me although Turner syndrome itself is a rare condition, we as humans are actually all rare. We each have a unique genetic makeup, which impacts our own health or that of our loved ones.

In fact, I wonder how many people have not responded to medication the way they should or why a child didn’t respond to the same treatment as another child. If we are all rare in our own genetic makeup than is “rare” actually common? It’s so common, and that’s why it takes All of Us to really understand and advance innovation in research with the hope of new treatments and cure for disease.

Commitment to Research

We are very fortunate here in Kansas City to have the commitment to bring a healthier future to our entire community. We are home to some of the top medical innovation in the country and although sometimes we are thought of as the “fly over” state, I would argue that we should be thought of the “fly to” state for medical treatment, research and innovation.

But it will certainly take All of Us to make that happen. Each one of us can choose to be ONE of the million people that will participate with research and make a difference not only for my daughter Allie, but also for you and your loved ones that may someday join us in this journey.

Learn more about the Children’s Research Institute at Children’s Mercy.

Learn more about Pediatric Genomic Medicine at Children’s Mercy.

Learn more about the Turner Syndrome Clinic at Children's Mercy.

by Elise Reuter

Dr. Tomi Pastinen’s insistence on finding answers brought him to lead the Center for Pediatric Genomic Medicine at Children’s Mercy. After building an 18-year career at McGill University in Montreal, the prospect of using his research to directly help patients lured Pastinen to Kansas City in July.

“What we couldn’t do there that I can do here is walk up to a clinician and ask, ‘What sort of problems do you have in your clinic?’” Pastinen said.

Back in Helsinki, Finland, where Pastinen was born, the same motivation drew him to genomics as a hopeful university student. Originally, Pastinen wanted to pursue physics and chemistry, but his family persuaded him to pursue a degree in medicine.

“I always felt that I’m a science geek,” he said. “I just love data.”

Read the full article via the Kansas City Business Journal.

Learn more about the Center for Pediatric Genomic Medicine at Children's Mercy.

Learn more about Children's Mercy's Children's Research Institute.

Children's Mercy has six physicians, 12 clinical genetic counselors and four laboratory genetic counselors providing state-of-the-art evaluation, diagnosis, treatment and counseling for a variety of inherited conditions.

Members of the team recently conducted a Lunch and Learn covering topics such as when to suspect a genetic disorder; components of a genetics evaluation; and interpretation of various genetic tests. The presentation proved so popular that the team has received numerous requests to repeat it for other departments throughout the hospital.

“The demand from families for genetic testing is exploding,” said Holly Welsh, Genetic Counselor Manager. “Children’s Mercy has the largest genetic counseling group in Missouri and Kansas. Our group gathers and analyzes pertinent information, then synthesizes it in a way for parents and providers to understand. We determine the best tests, help the family find the most economical way to pay for the tests, provide a concise explanation of test results, and recommend next steps.”

Caitlin Lawson, Genetic Counselor, said, “More often than not, the referrals we receive are for patients who have a presenting symptom that has come to the attention of a pediatric provider.”

Growth issues, congenital anomalies, and developmental delays of varying severities are common reasons for referrals and the first step for the Genetics team is to compile background data.

“We’re trying to put together the pieces of a puzzle,” Caitlin said. “We collect records, images and any other available data before the patient even walks through the door.”

Genetic testing is not always appropriate, but when it is, another significant block of time is spent explaining what types of tests are available to families and providers. The best summary of genetic tests types remains the classic “library” analogy: in a library, there are books on a shelf containing valuable information. A chromosome test is the equivalent of a librarian counting the books on a shelf, making sure there’s the correct number, but not opening any books; a microarray looks for missing or extra chapters. It provides more detail than the chromosome test, but doesn’t provide the finest level of detail; next generation sequencing is like reading through each book looking for typos.

Test expense and coverage

Genetic tests can be expensive, and as they become more sophisticated costs increase, with insurance companies increasingly denying coverage.

“The high cost of testing is something that frequently comes up, and I’d say consumers are generally unaware of the cost of genetic testing,” Holly said. “We spend a lot of time walking through what each of these tests does or doesn’t do—which is almost more important—how long they take, how expensive they are, insurance coverage, technologies involved and the number of tests required to access a particular diagnosis.” Costs can range from several hundred dollars for single gene testing to more than $10,000 for whole genome sequencing.

Kendra Engleman, Genetic Counselor, said when genetics testing is ordered at Children's Mercy, the case automatically goes to the insurance precertification department. Orders are also reviewed by laboratory genetic counselors to ensure that the most appropriate and affordable genetic test is selected for each patient.

“Even if a family gets an approval from their insurance to run the test, they still may get a substantial bill if they haven’t met their deductible for the year, or have co-payments,” Kendra said. “If testing will not be covered, we try to find options for getting testing completed at a more economical cost to the family.” Having awareness of these issues and engaging the family in the decision-making process leads to increased patient satisfaction.

After what can prove to be a lengthy process, hopefully a targeted therapy can be identified; however, clear-cut answers are not always forthcoming.

“That’s the really challenging part,” Caitlin said. “We counsel families on the front end that we may get a positive answer that clearly provides a diagnosis for them, but quite often we get ‘variants of uncertain significance (VUS),’ which is a technical term for ‘We don’t have enough information right now to call this variant conclusively benign or disease-causing.’”

Benefits of genetic testing

But even if nothing can be done directly, testing provides three benefits, Holly said. “It can answer the question of ‘Why?’ which parents almost always want to know; testing can offer a prognosis, which is really important for these families; and it can assess risk of recurrence, which can be valuable in family planning,” Holly said. “Even if we don’t have a cure, we can answer those three important questions, and we try do it in a way that is compassionate, educational and appropriate.”

Providing resources

Making families aware of resources available to them is another point of emphasis for the Genetics team, including websites, support groups and handout information.

“We’ve compiled a knowledge base that connects kids and families who have the same real-life issues even if they have different diagnoses,” Caitlin said. “Whether it’s formulating an IEP (Individualized Educational Program) for school or connecting families who have complex medical needs due to totally different reasons.”

‘Keep asking’

Even if treatments aren’t available currently, or expenses are prohibitive, the swift progress of genetic testing technology makes the Genetics team encourage families to “keep asking.”

“We see the landscape of genetic testing and research changing so rapidly that even if we have no answers to offer you in 2018, that’s not to say that can’t change in the years to come,” Holly said.

Learn more about the Division of Clinical Genetics at Children's Mercy.

Pharmacogenetics is increasingly utilized to advance individualized drug therapy as the health care industry shifts to value-based care. Not every patient responds to medications the same way and genetic factors can help determine how a person metabolizes drugs, and why a drug may or may not work.

There have been huge advances made in DNA testing to guide drug choice and dosage in children and adults, and it’s this individualized approach of treatment, instead of the one-size-fits all model, which will position pharmacogenetics and genomics at the leading edge of precision medicine.

Evolution of Drug Metabolism: The Animal Plant Warfare

To help understand why individuals respond to drugs differently, one needs to look at how drug-metabolizing enzymes have evolved over time, specifically those encoded by the cytochrome P450 (CYP 450) supergene family. P450 enzymes are noted for their high degree of inter-species and inter-individual variability, which has been attributed to animal plant warfare.

Certain plants produce toxins that prevent animals from eating them. In return, animals and humans developed defense mechanisms including CYP enzymes that allow their bodies to metabolize and get rid of potentially harmful chemicals, so they can ingest the plants. Many CYP enzymes can metabolize many drugs and a given drug is often metabolized by more than CYP. This redundancy helps protect animals and humans from toxins in plants and other environmental chemicals.

The vast majority of drugs are not natural products, but many are derivatives from substances originally found in plants or other organisms. This is why a lot of these enzymes that have evolved to protect us from everything we're exposed to could also be the enzymes that metabolize many of the drugs available today.

Given this evolution, it is easy to understand why individuals have genetic outfits that translate into a wide range of activity: some people have no or low enzyme activity of a particular CYP enzyme while others are at the opposite end and have very high activity; for other CYPs, a person might just have the reverse or what is considered normal activity. Depending on the environment, one or the other might be better suited to survive. So depending on a patient’s genetic make-up, s/he may respond well to a drug or not at all or even experience side effects.

Individualized Approach to Drug Dosing

Drugs and dose recommendations are developed for the average person, but what if you’re not the average person? There are many case reports describing patients who tried different drugs year-after-year but never found a therapy that worked for them. It wasn’t until pharmacogenetic testing was finally done and it turned out they were, for example, an ultra-rapid metabolizer, meaning they had an extra functional gene copy that made them metabolize the drug extremely fast. Or, on the opposite end, both of their gene copies had variations that renders them non-functional making them a poor metabolizer.

It is mostly patients with these extreme metabolizer phenotypes that benefit from drug dosing that is different than usual. Giving an ultrarapid metabolizer the standard dose of a medication often doesn’t work since their bodies metabolize and clear the drug too quickly, and they never reach the level of exposure required for the drug to be effective. One solution may be to increase drug dosage, which you would never do for the average person, or switch to a medication from a different drug class that utilizes a different pathway. For a poor metabolizer, the dosage may need to be decreased since the exposure to the drug will be too high as the body metabolizes the drug slower than usual.

Another good example where being a poor or ultrarapid metabolizer may have a significant impact is with the pain medication codeine. Codeine is in itself a drug that is not active, but instead needs to be bio-activated into a morphine derivative. If the body is a poor metabolizer and can’t form the morphine component, the patient may not get the desired pain relief. On the other extreme, if the person is an ultrarapid metabolizer the morphine metabolite may reach dangerously high levels that have been reported to be deadly.

Taken together with all the variability in drug metabolism, it can be challenging to find the right dose, for the right drug in both adults and children. As we learn more about the genes that contribute to drug metabolism and drug transport and how their variants effect their function, we improve our ability to predict what a drug response will be in the individual patient.

The ultimate goal is to really take out the guess work. By taking a patient’s history, their ethnic background, the family history and genetics into account, we hope to find better starting points for drug therapy.

Preemptive Genetic Testing

Would there be benefit to doing preemptive genetic testing early in a person’s life, so the information is available when needed later on? Unlike a lot of medical tests, genomic testing can be relevant for an individual’s entire life. For instance, if a physician has a newborn’s pharmacogenetic profile on record, when that child comes back as a teenager they can use that information to help prescribe the most effective drug for that particular patient.

Currently, pharmacogenetic testing is often done in retrospect, for example when a drug doesn’t work or the patient experiences side effects. We see many kids in our GOLDILOKS clinic that have tried a long list of drugs without success as well having experienced side effects such as weight gain, poor sleep, or drowsiness, to name a few. Pharmacogenetic testing can help prevent putting patients through this trial and error and avoid wasting time on something that’s never going to work.

Sharing Actionable Data

Given the wide range of genetic variation in the genes that contribute to how the body processes a drug, it’s important as an industry that we all speak the same language and use the same definitions when referring to genetic variants. Many health care professionals have not learned about pharmacogenetics in their training and may therefore not utilize such testing in their own practice. Increasingly, pharmacogenetic data are available to patients through direct-to-consumer testing, meaning that patients walk into their doctor’s office with their own pharmacologic genetic results. While the test results can be informative, they can also be overwhelming and a physician may not know what to do with them. To help health care professionals interpret pharmacogenetic tests, the Clinical Pharmacogenetics Implementation Consortium (CPIC) has published guidelines for many gene-drug pairs. Guidelines such as these help physicians determine the best course of treatment based on the patient’s genetic makeup.

In addition to standardizing definitions, it’s also important to have a single place to keep track of genetic variation and encourage stakeholders to share their data. Right now, data is sitting in silos in hospitals and data centers around the world and we need to get the information into a centralized repository so that everyone can make use of it. Our hope is that the new Pharmacogene Variation Consortium (PharmVar) database will serve as a global resource for both standardization and data sharing.

Pharmacogenetics is clearly not the only answer for making drug prescription more effective, but it can be an important piece of a larger strategy to move individualized drug therapy forward. Genomic approaches are here to stay and will be the next frontier for improving patient outcomes in everyday health care.

Learn more about Pharmcology and Toxicology at Children's Mercy.

Learn more about Clinical Pharmacology Research at Children's Mercy.

Kansas City is on its way to becoming an international hub in genomic research and the fight against pediatric diseases.

Two major endowments totaling $150 million last month are being used to lure top-notch pediatric research scientists to study and combat rare diseases in children.

Dr. Tomi Pastinen is director of the Center for Pediatric Genomic Medicine. He led a genomic research lab in Montreal for 15 years before taking a position at Children's Mercy last year. Pastinen says the availability to help patients so close to him drew his interest.

"And the whole team taking care of patients which really allows us to rapidly deploy genomic tools in more or less a bedside manner," he says.

Children's Mercy already features the first genome center in a children's hospital. The genome research aims toward finding solutions for complex issues in kids regarding DNA sequencing and analysis, including heart disease, diabetes and cancer.

Read the full article via Public News Service.

Learn more about the Children's Research Institute at Children's Mercy. 

Dr. Sarah Soden, Director, Center for Pediatric Genomic Medicine

Rare diseases may be “rare,” but collectively they’re quite common and affect up to 30 million Americans, which is nearly one in 10 people. Half of those are children.

To really grasp how many people are impacted by rare disease, picture this. The National Organization for Rare Disorders says if everyone with a rare disease held hands, they would circle the globe almost one-and-a-half times. When you start to talk to colleagues, friends and neighbors, you begin to realize just how many families are dealing with rare diseases.

What are Rare Diseases?

Any disorder, illness or condition that affects fewer than 200,000 people is considered a rare disease.

It's difficult to put a finger on how many distinct rare disorders exist because our understanding of them has changed so rapidly in recent years. This is especially true for disorders caused by mutations in a single gene. Nearly 7000 inherited disorders have been recognized in humans. When I first joined the Genome Center at Children’s Mercy in 2011, the cause was only known for about 2,500 of these. That number has since doubled to over 5000, which is great news, but our work is not done. Many families are left without answers. And even among the rare disorders whose causes are known, treatment options are limited.

Rare Disease Diagnosis

For patients whose conditions do have effective treatments, early diagnosis can be transformative, even lifesaving. But, the power of early and accurate diagnosis is bigger than that. It may lead to an awareness of other tests that are needed to catch the effect on other organs such as the heart or kidney early. Or steer us away from treatments that may be ineffective, even harmful.

Identifying the cause of a rare disorder allows specific genetic counseling to occur so families can begin to understand whether or not other relatives might be at risk. And of course, for many, getting an answer to "why" helps as they adapt to the challenges of having a rare disease in their family.

In my clinic as a Developmental Pediatrician I see this first hand. When I started 15 years ago, it was unusual for our families to come in knowing the cause of their child's rare disorder. Now we see it every day.

Genetic Testing and Research

Research is extremely important when it comes to studying rare diseases, because it leads to new breakthroughs in diagnosis and treatments. Genomic sequencing technologies are continually becoming less expensive and more widely available across the country. Technological advances will continue to increase the rate of diagnosis through additional discovery and better detection. For example, when we sequence a genome, we do it chunks (called reads) and line them up together. However, the technology is improving and the lengths of these reads is growing which allows us to detect genetic changes that used to allude us.

Sometimes what we learn from studying rare diseases teaches us about the overall human biology, which can be applied more broadly across medicine. One of the exciting directions the Genome Center Children’s Mercy, is taking is a move toward a broader “integrated genomics” approach to help us understand what’s going on in complex diseases. Integrated genomics combines numerous next-generation sequencing methods to understand the effect of a disease on the body and allows deeper investigation into the relationship between genes, environment and disease.

Advice for Parents

There's not a one size fits all approach to dealing with a diagnosis.

Find a support system. Many families enjoy the opportunity to connect with other families whether or not they have same disorder, because the struggles are the same whether it’s navigating education systems, sub-specialty clinics or the change in the parenting dynamics. All these things are common across many conditions, even if you’re not battling the same rare disease. A really good organization here in Kansas City is The RareKC Project. Another good source of information is the National Organization for Rare Diseases.

Be organized. Having a rare disease usually means you’ll be dealing with complicated health care. Make sure you have a digital file (or notebook) with all your child’s medical history. This way you’re prepared for all your appointments and you’ll feel a sense of control.

Feel empowered. You’re the expert of your child. Let your doctor or school district know if there’s a better way to interact with you. If it doesn’t feel right, speak up. Your voice is not just important, it is perhaps the most crucial tool your family has.

Learn more about Pediatric Genomic Medicine at Children’s Mercy.

Learn more about Children’s Research Institute at Children’s Mercy.

The Children’s Mercy Center for Pediatric Genomic Medicine is offering a four-day CME/CEU program for researchers and healthcare professionals interested in translational genomics. Click here for event dates and registration.

Waiting times for kidney transplants exceed 3 to 5 years in many parts of the United States. Yet more than 500 high-quality kidneys from deceased donors with hepatitis C virus (HCV) infection are discarded annually. Direct-acting antiviral agents, which are associated with high HCV cure rates and manageable side effects, have created the potential to substantially increase the number of kidney transplants by making HCV-infected kidneys available to HCV-negative candidates on the waiting list.

In this open-label, single-group, pilot trial at the University of Pennsylvania, we sought to determine the safety and efficacy of transplantation of kidneys from HCV genotype 1–viremic donors into HCV-negative patients, followed by elbasvir–grazoprevir (Zepatier) treatment. An external data and safety monitoring board reviewed all aspects of the trial. The authors vouch for the completeness and accuracy of the data and analysis and for the adherence of the trial to the protocol, available with the full text of this letter at NEJM.org.

Adults who were undergoing dialysis and who had long anticipated waiting times for a kidney transplant were eligible for inclusion in the trial, and patients with conditions that substantially elevate the risks of liver disease, allograft failure, or death were excluded. A physician-led, three-step, informed-consent process was implemented.

Deceased-donor criteria ensured selection of high-quality kidneys. Since elbasvir–grazoprevir is not approved by the Food and Drug Administration (FDA) for patients with HCV genotypes 2 or 3, and a direct-acting antiviral agent for the treatment of patients with those genotypes who have renal failure has not been approved by the FDA, donors were limited to those who had positive qualitative HCV nucleic acid test results and HCV genotype 1. We developed a new protocol for donor genotyping concurrent with organ allocation.

Intravenous glucocorticoids and rabbit antithymocyte globulin were administered to all recipients, followed by oral tacrolimus, mycophenolate mofetil, and prednisone. The HCV viral load was measured in recipients on postoperative day 3; elbasvir–grazoprevir was initiated when the results became positive, and therapy was maintained for 12 weeks.

Read the full article via The New England Journal of Medicine.

Learn more about the kidney transplant program at Children's Mercy.

A familiar face at Children's Mercy is listed alongside Drew Barrymore, Jessica Seinfeld, Melissa Bernstein (of Melissa & Doug), TV anchor Gretchen Carlson and other amazing women as neurodevelopmental pediatrician Sarah Soden was honored among Family Circle's 20 Most Influential Moms. Read her profile below, and you can find the entire list here. 

The Medicine Woman: Sarah Soden, MD

Neurodevelopmental pediatrician and director of the Center for Pediatric Genomic Medicine at Children’s Mercy Kansas City, age 46

Mother of Benjamin, 16, and Samuel, 14

When Sarah was in grade school, her class got to job-shadow and she chose to follow her pediatrician. That early experience set her on the path to her life’s mission. As director of the center, Sarah and her team use groundbreaking genetic testing to help uncover elusive diagnoses affecting infants and children.

I’m honored to work with families whose children have special needs. When I can be of service to them, it makes my day. Sometimes that includes using genome sequencing to solve a difficult diagnosis, which is particularly fun because it brings my clinical and scientific roles together.

When I first began to learn about genomes and gene sequencing, I was overwhelmed by the lingo and the rapid pace of technological advances. Mastering it all seemed truly impossible. So instead of trying to do that, I just tackled manageable pieces, one at a time.

The qualities that got me where I am today are curiosity, flexibility and a willingness to fail.

My mother was an educator for students with disabilities. She taught me to care about all kinds of children, especially the ones that need us most. Also, I don’t think I could have thrived as a working mother without her assistance.

My children are teenagers now, and I love that they are starting to express independent authentic opinions about their world. They are both tuned in to issues of social justice, which makes me so proud.

See the rest of Family Circle's 20 Most Influential Moms.

Learn more about the The Center for Pediatric Genomic Medicine at Children's Mercy.

At the annual Pediatric Genomic Medicine and Precision Therapeutics Conference (April 6-7), Children’s Mercy will again bring together thought leaders from around the world who are interested in advancing professional knowledge in genomics and precision medicine. Attendees will learn about new discoveries and gain a practical understanding of how to apply what they learn in a clinical setting.

The conference is geared toward pediatric sub-specialists, pediatricians, genetic counselors, laboratory medical professionals, bioethicists, psychologists, nurses, pharmacists and parents.

Visiting from the Emma Children’s Hospital, Academic Medical Centre in Amsterdam, Dr. Clara van Karnebeek will deliver the opening keynote, “Integrated Genomic & Metabolomics Analyses for the Discovery, Diagnosis and Treatment of Neurometabolic Disorders.” Other sessions include “Strategies for Implementing and Incorporating Genomic Medicine into Everyday Practices,” “Genomic Diagnostics: What We Know, What We Don't and the Space in Between” and “Genomic Sequencing: The Good, the Opportunities for Improvement and the Future,” “Custom-made Statin Therapy in Kids: Chop Cut Rebuild”

In his session, “Using Individualized Patient Information to Improve Clinical Care,” Dr. Girish Shirali of the Ward Family Heart Center at Children’s Mercy will discuss the Cardiac High Acuity Monitoring Program (CHAMP), which recently won a Microsoft Health Innovation Award. On average, 1 in 5 babies born with single-ventricle heart defects die at home between two necessary surgeries. CHAMP connects families to their medical teams using real-time analysis of vital statistics and videos. Since 2014, CHAMP has reduced interstage mortality at Children’s Mercy from 20% to 0.

The Genomic Medicine Center at Children’s Mercy was created to help unlock the mysteries of pediatric genetic diseases. Here, a diverse team of specialists are developing new, better and faster ways of diagnosing genetic causes of disease and changing the way medicine is practiced around the world. The first of its kind to be located inside a children's hospital, the Center is also the world's first focused on genome sequencing and analysis of inherited children's diseases. Working with the most advanced technology and scientific knowledge, the Center is already developing new genome analysis and computation capabilities to improve diagnoses and care for pediatric patients.

More information and registration for the conference.

Learn more about The Center for Pediatric Genomic Medicine.

At a visit to the Children’s Mercy Kansas City Orthopaedic Clinic, 12-year-old Devin Corwin-Herrick was the picture of confidence—smiling and tanned as he waited for his doctor, Richard Schwend, MD, FAAP, Director, Orthopaedic Research Program.

Clearly, Devin doesn’t let the fact that he has a rare connective tissue disorder get the best of him. He has better things to do, like play X-box, or hunt, or hang out with his best friend, Brayden. But that wasn’t always the case.

At birth, Devin’s mom, Stephanie Lewis, said it was clear something was wrong with her baby. “A nurse at the hospital where Devin was born shoved a flier on Marfan’s Syndrome in front of me and said, ‘This is what your baby has.’”

That was the beginning of a diagnostic and treatment odyssey that’s taken Devin and his family from his small Kansas hometown of Alton to Kansas City, Iowa City, Iowa, Baltimore, and back to Kansas City again.

At just 2 years old, Devin needed surgery to stop the vertebrae in his neck from compressing his spinal cord, preventing severe deformity and possible paralysis. That’s when Stephanie began to question whether Devin actually has Marfan’s Syndrome, a genetic disorder that affects the body’s connective tissues.

“Devin does have some of the characteristics of Marfan’s, but not all,” she said. Because Devin has two extra vertebrae in his neck, the physician who performed his first neck surgery suggested he might have an even rarer disorder called Loeys-Dietz Syndrome (LDS) instead.

“At that point, I didn’t want to put Devin through anything else, so I decided against genetic testing,” Stephanie said.

Complications

As Devin grew, so did the physical complications he was facing. That included complex surgery to reduce the size of his aorta when he was 7 years old. That operation was performed at Johns Hopkins in Baltimore, the hospital where LDS was first identified as a disorder in 2005.

With the outstanding cardiac program at Children’s Mercy, the specialist in Baltimore referred Devin back to Children’s Mercy for his ongoing cardiac care, saving the family from traveling across the country.

By now, Stephanie had researched Marfan’s and LDS, comparing the characteristics of both, concluding for herself that Devin might have LDS. Still, she wasn’t certain.

At Children’s Mercy, pediatric cardiologist, Robert Ardinger Jr., MD, also suggested testing to validate that Devin has Loeys-Dietz Syndrome. This time Stephanie agreed.

“It was just a blood test and the results only took a couple of weeks, but they confirmed what we had suspected, that Devin has LDS,” she said.

LDS is a rare genetic disorder marked by characteristics not usually seen all together in other connective tissue disorders. These include aneurysms, twisting or spiraled arteries, widely spaced eyes, skull deformities and a split or broad uvula.

Devin also has many of the skeletal characteristics of LDS, including long fingers and toes, clubfoot, joint laxity, scoliosis and cervical-spine instability. Surgery at Children’s Mercy in 2008 with Brad Olney, MD, Division Chief, Orthopaedic Surgery, tightened the ligaments in his left knee and ankle.

'...In really bad shape'

In the meantime, the degenerative nature of the disorder caused Devin’s spine to become more and more unstable. “Devin was in really bad shape when he came to see us,” Dr. Schwend said. “His head was literally sitting on his shoulder. He had lost most of the function in his left side. The extra vertebrae in Devin’s neck were compressing his spine. Our goal was to stabilize Devin’s spine, remove the two areas that were compressing the spinal cord in his neck, and improve function.”

To do that, Dr. Schwend started by placing Devin in halo traction for a month, straightening his head and neck as much as possible prior to operating, and making surgery safer.

A multidisciplinary team including Dr. Schwend, John Clough, MD, neurosurgeon, and Jill Arganbright, MD, pediatric otolaryngologist, stabilized Devin’s spine in two separate six-hour operations. The first was performed in February 2015 on the back of his neck, and the second in July 2015 on the front.

High-risk surgery

“This was a very high-risk surgery,” Dr. Schwend said. Dr. Clough made sure the vertebral arteries weren’t compromised and performed the decompressions in the back, as well as the front of Devin’s spine. During the July surgery, Dr. Arganbright helped navigate Devin’s complex anatomy so the team could reach the problem vertebrae safely. “Their collaboration is what made Devin’s surgery possible.”

“Going in to the operation, we knew Devin’s odds weren’t good, but Dr. Schwend was always very honest with us,” Stephanie said. “He told us what they could do and what to expect.”

Initially, Devin’s recovery was difficult, but one year later his function and quality of life have improved greatly. In fact, when Dr. Schwend asked if he’d had a good summer, he grinned and said, “Yes! I’ve been fishing and camping. It’s been great!” A seventh grader at Osborne Middle School, Devin’s favorite subject is science. He and his best friend are helped with the football team, and he is active in Special Olympics.

CM: Fighting for Devin

With 16 surgeries in 12 years under his belt, Devin is a veteran patient who knows more physician visits and operations are likely in his future, including possible dental surgery and knee surgery. “I probably hold some kind of record,” Devin said.

Through it all, Stephanie said it’s the doctors and nurses at Children’s Mercy who have helped their family find the answers to the complex questions surrounding Devin’s diagnosis and treatment.

“I’ve taken Devin to hospitals all across the country to try to get him help,” Stephanie said. “When others were reluctant to do anything because it was too risky, the doctors and nurses at Children’s Mercy were willing to try … to fight as hard for Devin as I do. That’s what makes this place so special.”

Learn more about pediatric orthopedics at Children's Mercy.

Learn more about The Children's Mercy Division of Clinical Genetics.

For some treatments, the perfect dose is a necessity. Leukemia patients, for example, take busulfan to prepare 

for a bone marrow transplant. Too little, and the patient’s body won’t accept the transplant. Too much, however, can cause irreversible liver damage.

“It’s a really fine line,” said Susan Abdel-Rahman. 

director of the pharmacokinetic and pharmacodynamics core laboratory at Children’s Mercy.

She created a platform to help determine how much is “just right” based on a child’s genome and age. Named GOLDILOKs after the children’s story, the program gathers data about how pediatric patients 

process medication, looking at factors such as genetics and age.

“We’re interested in making medications more effective for kids,” said Steven Leeder, director of clinical pharmacology and therapeutic innovation for Children’s Mercy. “People try to scale adult data for kids. ... How would you scale a dose from a 70-kilogram adult to a 1-year-old?”

As researchers gather data on a child’s reactions to a medication, they also are able to gather population data to see how much variation there is among all pediatric patients.

“We’re looking at how things change during growth and development,” Leeder said. “The pathways to get rid of foreign chemicals come on after birth.”

The project began when Leeder tested this concept with atomoxetine, a common ADHD drug better known as Strattera. The drug had gained a reputation for mixed success, but the results depended on a drug pathway with significant genetic variation between patients.

Although the recommended dose for a drug is based on the average amount needed for the desired effect in patients, this approach doesn’t account for patients on either end of the bell curve. In the case of atomoxetine, 3 percent to 5 percent of the population processes the drug much quicker than average, experiencing less of the desired effect, whereas 7 percent lack the needed mechanisms to process the drug, resulting in too much of the drug.

Leeder’s shocking finding: The variation between those two extremes was 50-fold.

“It’s an extremely wide range,” he said.

The discovery motivated him to start looking at the individual “bullet points,” or patients, rather than the general response to the drug.

The key insight, Leeder said, was “trying to figure out what factors contribute to that data point being where it is — what we need to be doing to implement individualized therapeutics — rather than just lumping the data together to get a sense of how things are ‘on average.’”

To the clinic

In 2013, Abdel-Rahman developed the platform to help physicians interpret this data, rather than keeping it isolated from the clinical side. With information on a patient’s history and the general population’s reaction to a drug, the software can generate a line of best fit to tell physicians how much to prescribe.

“The value of the tool is to get (patients) managed more quickly and more efficiently,” she said.

The platform gives real-time results and is fully integrated with the patient’s electronic medical records for quick calculations. It essentially allows the physician to simulate a dose based on the desired effect for the patient. Although other hospitals have developed modeling tools, most don’t make it into clinical practice, driving interest in the GOLDILOKs software.

“What we do here, the problems we work on are driven by clinicians,” Leeder said. “Once you get to 100 kids, you start to see how much variability there is in (drug) exposure. That can drive a research question.”

Child development and genetics are the current focus of the GOLDILOKs program, but Leeder said researchers may look at other variables, such as a child’s environment.

“Part of the fun is coming up with these creative solutions,” he said. “We’re generating data where data doesn’t exist.”

For Leeder and Abdel-Rahman, this is just the beginning, as the program expands to several pediatric subspecialties. From Leeder’s study on ADHD, the model now is applied to studying statin drugs for cardiology, histamines for asthma patients and studies on how obesity affects a child’s response to medications.

“We’ve got a bunch of people who are not afraid to do something that hasn’t been done before,” Leeder said. “The information is there — we just need to pull it out.”

Read the story via the Kansas City Business Journal.

Learn more about GOLDILOKS.

Learn more about The Children's Mercy Division of Clinical Genetics.

Ryleigh Patience's passion, hard word and determination sets her apart from many girls her age. When she was three years old, Ryleigh was diagnosed with Hurler's Syndrome, a rare genetic disease that causes a buildup of sugar waste molecules on her bones, muscles and organs resulting in countless medical procedures, surgeries and stunted growth. She was told she would live to be ten "if she was lucky."

Now twelve, Ryleigh lives an active life playing softball - which is unique as many children with Hurler's Syndrome cannot participate in sports. Don't let her small four-foot-tall stature on the field fool you, Ryleigh is one special girl with an infectious smile and spirit.

Along with her love of the game, Ryleigh has a special relationship with the Mizzou softball team. When Ryleigh met her role model, Dot Richardson, at a collegiate tournament through Make-A-Wish, she also got the opportunity to meet the women of the Mizzou softball team. What resulted was Ryleigh becoming "something special" for the University of Missouri. Both players and coaches say Ryleigh is a part of the team. She is easily the most popular person in the ballpark, serving as an inspiration and reminder that there is more to life than just the game. She's an extraordinary girl with a fighting spirit, huge heart and an even bigger desire to be a part of the game.

Find out more about the WIN for KC awards.

Learn more about The Children's Mercy Division of Clinical Genetics.

Learn more about The Center for Sports Medicine at Children's Mercy.

With one of the larger inflammatory bowel disease (IBD) programs in the nation, the Children’s Mercy Division of Pediatric Gastroenterology cares for 550 to 600 patients and their families on an ongoing basis. Like many programs, the multidisciplinary IBD team includes gastroenterologists, nurse practitioners, a psychologist, social worker, nutritionist and researchers.

But it’s parent engagement that sets the Children’s Mercy team apart from other programs locally, regionally and nationally.

National collaborative encourages parent involvement

According to Julie Bass, DO, Medical Director of the Inflammatory Bowel Disease Program, the Children’s Mercy IBD program became involved in the ImproveCareNow Collaborative in 2011.

ImproveCareNow is an international quality improvement collaborative dedicated to improving lives of pediatric and adolescent patients with IBD. This collaborative has demonstrated remarkable success, increasing remission rates nationally from about 55 percent to nearly 80 percent, without prescribing any new medications.

“When joining the collaborative, we were encouraged to invite a parent to become an engaged participant on our IBD Quality Improvement team,” Dr. Bass said. “Though this idea sounds simple, it is not the dominant culture in health care.”

Partnering with parents leads to quality improvements

Immediately, Dr. Bass thought of Jamie Hicks, a parent whose son was inpatient at Children’s Mercy at the time. “Jamie easily stood out to me with her sense of passion, professionalism and purpose,” Dr. Bass said. “She knows she represents not only the voices of our IBD patients and their families, but also the thousands of IBD patients and parents living with this disease.”

“I am an expert in my child,” Jamie said, “but not in quality improvement or medical research.” At the first conference she attended, Jamie listened carefully to the conversations around her. “The Children’s Mercy Quality Improvement team kept asking me for my viewpoint and listened,” she said. “That inspired me to action.”

When Dr. Bass and Jamie returned to Kansas City, Jamie began to serve as member of the Quality Improvement team. “I was able to offer the parent’s perspective and bring ideas for improvement to the table,” she said. Together, they addressed issues such as phone line access, resulting in a dedicated IBD phone line, a list serve to share news about upcoming events, and discussions about continual quality improvement.

Expanding the parent and Family Advisory Council’s role

Though this initiative started with just one parent, in late 2014 it expanded to a full parent advisory council which partners with the Quality Improvement team and is called the Parent and Family Advisory Council (PFAC). The PFAC meets quarterly with Jamie serving as the liaison to the IBD team, sharing parents’ concerns and suggestions.

“One of the things the PFAC brought to our attention was the need for a clinic discharge form for each IBD patient,” Dr. Bass explained. After working together, the team developed a form that Dr. Bass said has changed the way she practices medicine.

“I am very conscientious and detail-oriented. I thought I provided the same level of care for every patient, but using this form has made it clear to me that there is more I can do. It’s well organized, straightforward, and a great tool to be certain every patient receives the same standard of care,” Dr. Bass said.

Other projects the PFAC has worked on include patient education materials, and a video created for newly diagnosed patients and families.

Advisory Council identifies opportunities for innovation

The PFAC’s next innovation is to create a Children’s Mercy app for chronic disease management that will be designed to help all children, not just those with IBD, become more engaged in their own care.

The Children’s Mercy program has been recognized as a leader in parent engagement through ImproveCareNow and other national organizations, including the Institute for Healthcare Improvement.

“This partnership has been extraordinary for our IBD team,” Dr. Bass said. “What really drives the work is what the parents are passionate about. The unique perspective of the PFAC allows our team to identify issues we were not even aware existed.”

As a parent representative to ImproveCareNow, Jamie has had the opportunity to compare notes with parents from across the nation about their engagement with other IBD programs. “The IBD Quality Improvement team embraces our perspective, actively involving our parents in decisions to improve patient care,” she said. “Children’s Mercy really is revolutionary.”

Learn more about Inflammatory Bowel Disease and the ImproveCareNow collaborative.

Learn more about the Division of Pediatric Gastroenterology at Children's Mercy.

From Elana Lyn

Dr. Sarah Soden is a neurodevelopmental pediatrician and the director of the Genomic Medicine Center at Children’s Mercy Kansas City. The center, founded in 2011, integrates clinical diagnostics with research programs featuring rapid whole genome sequencing, monogenic disease discovery, infant oncology, single-cell sequencing, and disorders of expression. Dr. Sarah Soden’s clinical practice involves the diagnosis and treatment of developmental disorders including intellectual disability and autism. Dr. Sarah Soden also directs a Genomic Medicine Master Class for pediatric subspecialists that uses self-sequencing and analysis to teach foundational principles of genomics.

How did you end up at the Genomic Medicine Center at Children’s Mercy? What was your career path? How did you land your role? What was the hiring process like?

My time at Children’s Mercy in Kansas City began with my pediatric residency. I attended medical school at the University of Missouri-Columbia. My original plan was to leave the Midwest because I’d been here my entire life. I was focused on other parts of the country for my residency, but then I decided to interview at Children’s Mercy (mostly to see some friends in town) and I fell in love with it. I loved it so much, in fact, that I stayed on to do a year as chief resident and then to complete a fellowship in neurodevelopmental disabilities. After residency, I worked for several years as a developmental pediatrician, caring for children with developmental disabilities.

During my training and early years as a clinician, I could never have imagined the path my career would take. Who would have thought I would end up in a Genome Center? I’m not a geneticist, but a desire to learn and the support of my institution has given me the opportunity to diversify and rise through the organization.

What are your responsibilities as director of the Genomic Medicine Center at Children’s Mercy?

I lead a team that uses genomic testing to uncover elusive diagnoses, saving time and money, and changing treatment for infants and children. Our team runs the fastest clinical whole genome analysis in the world, named one of TIME ’s Top 10 Medical Breakthroughs in 2012. We also are studying the cause of a diverse array of diseases like infant leukemia, childhood kidney disease, developmental bone disorders and Tourette syndrome.

What has been your proudest moment from your career so far?

My proudest moments are when families can finally receive an answer to the question: “What is the reason for my child’s symptoms.” It’s sometimes the end to a diagnostic odyssey. It can be a turning point in terms of how the family views the condition of their child and how they’re able to communicate what’s going on to teachers, neighbors, and family members. It’s oftentimes just a relief for them to be able to say, “It’s this condition. It’s this syndrome,” and they don’t have to worry and wonder and think. It just closes that chapter of trying to find the answer.

What are the most important characteristics someone needs to have to be successful in your role?

Humility and the ability to accept support are critical to success. I’m surrounded by working moms who support one another. On days when I feel like I’m failing, my co-worker mom friends are there to tell me it is okay. On the days when we knock it out of the park, we’re all cheering for each other. Almost all of the directors of the Genome Center are women, which is rare and creates a unique, supportive environment. The women who lead this team are very intellectually generous with one another. They’re willing to teach. We respect one another, we respect the patients we’re trying to help, and we respect good science that makes a difference for kids.

What is on your desk right now?

On my desk is a photo from my last medical mission trip to Haiti. It’s a picture of me and my colleague and friend, Dr. Jennifer Lowry, and we each have a young girl on our back. Jennifer and I were on the beach one day and there were two young girls running toward us. They kept saying “blanc, blanc,” because of our white skin. As they were looking curiously at our pale skin, we realized it was the middle of the school day, and they should be in school. The church rectory where we were staying was on the same street these little girls live on, and the person who runs the rectory told us the girls’ mother was not able to afford to send them to school. We decided to donate enough money each year to buy their uniforms and books and pay their tuition. I’m looking forward to returning next year for another medical clinic and to see how the girls are doing.

What is your favorite thing about working at the Genomic Medicine Center at Children’s Mercy?

One of my favorite things about working here is solving mysteries. When I was involved in clinical and research work, I didn’t appreciate how beautiful it is to have an answer. In my early years as a developmental pediatrician, a lack of answers was the case more often than not. Now, just the experience of being in clinic and being able to say, “Yes, we do have an answer,” is rewarding. However, it’s also critically important for that answer to be right. That need for accuracy drives all of us to operate at a high level of excellence. The work we’re doing here is just scratching the surface and I’m excited to discover more.

What is a day as Dr. Sarah Soden like? Please walk us through a day.

There is no such thing as a typical day, and that suits my personality pretty well. Some days I see patients in the clinic. Most of my patients are children with disabilities that I’ve followed for years. Other days involve meetings and work on scientific or clinical projects with the genome center team. This year I’ve spent a lot of time writing – mostly research proposals. Grant funding is very competitive these days, so proposals take a lot of time and effort.

What is your career advice for other young professional women?

Don’t be too proud to ask for help. Many women who are high achievers are used to being able to accomplish whatever they set their minds to. Over time, we get the idea that we can and should accomplish our goals independently. This can be especially difficult for professionals who are also young mothers. Also, be aware of your value at work. Women tend to be helpers, which means we often put the needs of others ahead of ourselves. Sometimes your needs, goals, and accomplishments should take center stage.

Learn more about The Center for Pediatric Genomic Medicine at Children's Mercy.

Read the entire Dr. Soden profile by clicking here. 

A study at Dartmouth-Hitchcock Medical Center, which provided telemedicine services to the predominantly rural populations of Vermont and New Hampshire, showed that although patient and provider satisfaction with the model were high, approximately 19% of patients seen via telemedicine were not appropriate candidates, either because of an unclear diagnosis or substantial disease complexity. This suggests the need for triage mechanisms that minimize such inappropriate referrals.

Telemedicine can improve healthcare access, patient outcomes, and costs, although it presents several potential obstacles. Expanded insurance coverage of this modality will be necessary to greater numbers of patients in need of specialty care.

For Elizabeth Kessler, MD, MS, a pediatric rheumatologist at Children's Mercy who co-authored the study there, the training of the clinical “telefacilitator” — often a nurse — at the patient site influences the types of patients she will see remotely. “For example, the nurse facilitator who I work with spent time in the rheumatology clinic learning how to perform a joint exam and distinguishing between active and inactive arthritis,” she explained.

“Using her examination in addition to what I am able to visualize, I feel comfortable making changes in patients' medications. If the facilitator did not have this training, seeing such patients and making treatment changes may not be appropriate.”

Barriers and Solutions

Whereas the benefits of telemedicine are clear — including improved access, outcomes, and patient satisfaction, and lower costs, for example — there are also multiple potential barriers. Insurance reimbursement is one of the primary issues, although progress has been steady if sluggish in this area. “Currently 29 states have mandated that commercial insurance cover telemedicine encounters. However, rates of reimbursement vary and depend on where the patients are located for the visit, what services are covered, and the type of provider who is seeing the patient,” and such variability can be a deterrent, according to Dr Kessler.

Despite the success stories, skeptics remain. “Reservations among rheumatologists exist about whether visits can be effectively conducted via telemedicine. Therefore, future research needs to address the ability to perform an accurate musculoskeletal exam via telemedicine,” said Dr Kessler. “Comparing process and outcome measures between patients seen in traditional in-person clinic visits versus those seen by telemedicine would be another way to ensure that telerheumatology visits can provide high-quality care.”

Read the full story via Rheumatology Advisor.

Learn more about rheumatology or telemedicine.

The Kansas City Business Journal recently featured Children's Mercy Chief Scientific Officer Dr. Tom Curran, executive director of the Children’s Research Institute, as one of Kansas City's newsmakers. Here is an excerpt of that profile, which you can read in its entirety here. 

Curran said it felt like coming home when he visited Kansas City with his wife, Jessie Ng, who also researches pediatric brain tumors.

“The Midwestern mentality was kind of similar to the Scottish working mentality I’d grown up with,” he said. “Of course, Children’s Mercy was something very special.”

Another pull was the local arts, including the Kansas City Ballet, where their 13-year-old dances. She performed in “The Nutcracker” this year.

“Kansas City has all of these features that aren’t necessarily proclaimed to the world but act as an incredible draw for recruitment,” Curran said. “The concentration of artistic talent here is really amazing.”

The same philanthropic network that helps boost the arts will be key to growing the institute, Curran said. With several organizations already in place, Children’s Mercy will work with The University of Kansas Cancer Center, University of Missouri-Kansas City, Stowers Institute for Medical Research and others to further its research efforts.

“I’m a great believer in leveraging existing advantages,” Curran said. “That’s the key in our future success — figuring out how we can work together.”

At Children’s Mercy, he will build on existing programs in genomics and clinical pharmacology. His wealth of experience will help speed this up: He’s worked with some of the world’s top institutes, published hundreds of articles and was president of the American Association for Cancer Research.

“Having this opportunity to build a research infrastructure seamlessly integrated with Children’s Mercy gives me a chance, in a sense, to put my money where my mouth is,” he said.

Read the entire Business Journal profile.

Learn more about the Center for Pediatric Genomic Medicine at Children's Mercy.