It was only 15 years ago that the first human genome sequence was revealed, the result of a huge National Institutes of Health project that spanned over a decade and cost $2.7 billion. This spurred a period of genomic discovery that has changed exponentially how we understand human health, with the field of pediatric medicine at the forefront. Today, mostly due to advances in technology that have dramatically reduced the cost and turnaround time of genomic sequencing, the newly established Roberts Individualized Medical Genetics Center (Roberts IMGC) at Children’s Hospital of Philadelphia can coordinate a genetic testing plan that provides patients and families accurate and comprehensive results within a few weeks.
“It is revolutionizing what we do in medicine,” said Ian Krantz, MD, an attending physician in the Division of Human Genetics at CHOP, who also codirects the Roberts IMGC along with Livija Medne, MS, LCGC, a senior genetic counselor. “We now have this power to do next-generation sequencing, and as tests have become more and more complex, and we’re able to understand more and more of the genome, testing in genetics has broader applications across all fields of pediatric medicine.”
This unprecedented growth of genomics was the impetus for creation of the $50 million Roberts Collaborative for Genetics and Individualized Medicine that launched in September at CHOP. It is the first program in the nation that will apply genetic testing technology to individualize diagnostics in pediatrics and then translate patients’ unique genetic blueprints to inform clinical management, family education and counseling, innovative research, and eventually new therapeutics.
A $25 million gift by the Roberts family made the Collaborative possible. CHOP is matching the gift with $25 million in internal funding, and together they will support multidisciplinary efforts that harness the energy and enthusiasm of genomics experts across the institution, including the Roberts IMGC, the Division of Human Genetics, the Division of Genomic Diagnostics, the Center for Applied Genomics, the Department of Biomedical and Health Informatics, The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, and others.
“We are extremely grateful to the Roberts family for this remarkable gift, which will help the Children’s Hospital of Philadelphia usher in a new era of genetics and broaden the scope of genetic medicine across all clinical areas of the hospital,” said Madeline Bell, president and CEO of CHOP. “Research is core to CHOP’s mission, and growing CHOP’s Research Institute is fundamental to our strategy and commitment to breakthroughs.”
CHOP’s new integrated approach that capitalizes on understanding the genetic underpinnings of childhood diseases already is making a difference in young lives. Dr. Krantz shared the story of 9-year-old Emily, who came to the Roberts IMGC after experiencing two years of progressive hearing loss. She had genetic testing for a panel of about 75 genes that are known causes of hearing loss, but the tests came back normal. Two years later, Emily returned after developing some visual loss. Dr. Krantz and his genetics team dug deeper for answers and analyzed Emily’s entire genome — all 20,000 genes in a single test.
“The results showed that she had a rare, one-in-a-million diagnosis for a progressive neurological disorder that would lead to death in early adulthood,” Dr. Krantz said. “Her genetic changes caused a problem in the way she metabolized a vitamin called riboflavin. This was very important for the family to know because both parents carried the same genetic mutation. We could counsel them about recurrence risk and prognosis. And even more exciting is that there was a treatment.”
Emily went on high dose therapy for the missing vitamin, and although her symptoms may not be reversible, her condition has stabilized. The genetics team also tested her asymptomatic 5-year-old brother and found that he also has the gene mutation. He is receiving treatment as a preventive strategy, and hopefully he will not develop any symptoms.
This family’s experience is a good example of where Dr. Krantz sees genomic medicine heading in the next decade — toward the screening of all newborns and individuals with genetic testing technology to give clinicians the opportunities to intervene early, such as by recommending lifestyle changes or prescribing pharmacologic therapies. Genetic testing may help to identify risk factors for many of the common diagnoses that adults face, such as diabetes, hypertension, and Alzheimers, that may be able to be managed and treated during childhood in order to improve outcomes throughout lifetimes, Dr. Krantz suggested.
The biggest stumbling block currently for genomic medicine is uncertainty. Scientists do not yet understand everything that they see in the genome, and that can sometimes be anxiety-provoking for families and clinicians. It also could lead to unnecessary tests that could increase healthcare costs. For instance, genetic testing may reveal that a child has a potential risk for a heart problem, but it may be unclear if the identified mutation will actually result in a damaging physical change. As a precaution, the child might need to visit a cardiologist once a year for an echocardiogram.
“Until we find a balance, or study and understand that the benefits outweigh those costs, people are a little hesitant to make genetic screening universal,” Dr. Krantz said.
In the meantime, the Roberts IMGC has three pediatric geneticists, Cara Skraban, MD; Kosuke Izumi, MD, PhD; and Matthew Deardorff, MD, PhD; and two genetic counselors, Emma Bedoukian, MS, LSCG, and Jennifer Tarpinian, LSGC, who ensure that families receive thorough clinical evaluations, education, and counseling before and after genetic testing on its usefulness and limitations. They also discuss families’ choices about the type of results that they want back. In some cases, families may only want answers to the possible genetic problems that their child is experiencing, while others may also want to know about secondary findings that could be medically important. The counselors meet with families about the results to explain their potential significance and put them in touch with specialists if needed.
So far, the Roberts IMGC has worked with about 2,000 patient referrals, and they continue to see about 100 patients a month, a number that Dr. Krantz expects will expand along with the availability of affordable genetic testing. As more medical insurance companies begin to acknowledge the utility of genetic testing, Roberts IMGC clinical coordinator Jasmine Montgomery navigates the nuances of pre-authorization and billing so that families do not end up with big balances to pay.
In many ways, genetic testing could be seen as a long-time investment in children’s healthy futures because it provides insights into their genetic predispositions that are never static. A central mission of the Roberts Collaborative is to integrate patients’ genetic makeup into their electronic health records so that this valuable information is always accessible and portable.
“We can test a 6-month-old’s genome today and not find an answer, but two years from now, we may go back and re-analyze that information and find one,” Dr. Krantz said.
Genomic medicine straddles both the clinical and research sides of CHOP. It may guide physicians in patient management, but it also generates a huge amount of data that, with appropriate consent from families, researchers can leverage to make discoveries to improve care. They can search for new genes or associations, figure out how changes in suspected disease genes are functioning, and translate that knowledge into developing therapies. Part of the Roberts IMGC’s goal is to invite every patient that they see to participate in a protocol approved by the Institutional Review Board to have their samples put in a biorepository to drive research. Already, the Roberts IMGC has found six brand-new genes that they are evaluating.
“I think the world is going to change dramatically,” Dr. Krantz said. “And it’s happening really, really fast, as far as medicine goes. It challenges all of us in genomics to constantly be at the cutting edge and stay on top of these breakthroughs so that we can translate them directly back to our patients, which is our mission here at CHOP.”