Neurodevelopmental disorders, such as intellectual disability, Tourette syndrome, autism and neuromuscular diseases affect more than 10 percent of children.
Recent advances in genomic medicine are unraveling the etiology of these disorders and providing answers to more patients and families.
These discoveries, along with advances in pharmacogenomics are the foundation of precision medicine.
This topic is important to many and is an area of focus regarding active studies being conducted within the Genome Center.
Hear from Sarah Soden, MD, on GSEND (Genomic Sequencing for the Etiology of Neurodevelopmental Disorders) a prospective study designed to determine whether genomic sequencing early in a child’s diagnostic evaluation improves diagnoses and transforms outcomes.
Selected Podcast
Neurodevelopmental Disorders: Studying the Clinical Impact of Genomic Sequencing
Featured Speaker:
Learn more about Dr. Sarah Soden
Sarah E. Soden, MD
Dr. Sarah Soden is a Neurodevelopmental Pediatrician and the Director of the Center for Pediatric Genomic Medicine at Children’s Mercy Kansas City. She joined the Center in March of 2011 leading efforts to integrate genomics into pediatric health care throughout the institution. Dr. Soden’s clinical practice involves the diagnosis and treatment of developmental disorders including intellectual disability and autism. Dr. Soden is a graduate of the University Of Missouri-Columbia School of Medicine. She completed pediatric residency at Children’s Mercy Hospital in Kansas City, followed by a Neurodevelopmental Disabilities Fellowship at The University of Kansas Developmental Disabilities Center and Children’s Mercy Hospital. Research interests include inherited intellectual disability, clinical and ethical implications of pediatric genomic medicine, and translational pharmacogenomics.Learn more about Dr. Sarah Soden
Transcription:
Neurodevelopmental Disorders: Studying the Clinical Impact of Genomic Sequencing
Dr. Michael Smith (Host): Our topic today is “Neurodevelopmental Disorders – Studying the Clinical Impact of Genomic Sequencing”. My guest is Dr. Sara Soden. Dr. Soden is the Director of The Center for Pediatric Genomic Medicine at Children’s Mercy Kansas City. Dr. Soden, welcome to the show.
Dr. Sara Soden (Guest): Thank you for having me. It’s my pleasure.
Michael: How many kids in America are affected by neurodevelopmental disorders?
Dr. Soden: It really depends on how you define them. When we think about more severe neurodevelopmental disorders like intellectual disability or children who meet full criteria for autism, the number is probably around 3-4%. If we begin to think about individuals with milder disabilities, such as language disorder or even ADHD, then we get above 10% in terms of number.
Michael: I know what you’re focusing a lot now on is genomic sequencing. Why don’t we start off with what exactly is genomic sequencing and why is it so important, in your opinion?
Dr. Soden: Sure. As most of our listeners probably know, the Human Genome Project really transformed our understanding of gene sequencing and the human genome in general. For example, we thought there were maybe 30,000-50,000 genes. Now we know there are only about 20,000 genes that people have. So, even on a very fundamental level, some of our knowledge has changed dramatically. More importantly for medicine, what the human genome project began was this revolution in technology. Now we have the capability and in institutions like ours of sequencing a person’s genome or just their genes which we call the “exome” for a cost that is relatively comparable to other types of commonly used genetic testing. Now, when we have a patient who comes in with a set of symptoms and an unknown reason for those, we can perform what we call exome or genome sequencing and oftentimes get an answer for that family. In the past, individuals with rare diseases or hard to detect genetic diseases would sometimes go decades without an answer, which can be very difficult for a family and oftentimes never get an answer. We’re really changing that now. We’re able to give that family a reason for the symptoms that they’re dealing with and allow them to sort of get past the asking of why and move on towards just really focusing on the child and what they need to do to meet the child’s needs.
Michael: Dr. Soden, in the adult world, what we might do is look at something like depression or anxiety and we can discover polymorphisms that are common to that population of patients. Then we could look at somebody’s DNA, we can sequence it and look for those polymorphisms and let that patient know “you might be at an increased risk because you have that association”. How does it work exactly? How does genomic sequencing work exactly for children with neurological disorders?
Dr. Soden: What we’re really looking for is something quite different than what you’ve described which is a very sort of powerful tool as well but what we’re looking at are inherited diagnoses. For example, when I sit down in front of a variant file--and that means when we run someone’s exome or genome--we get a file that our bioinformatic tools give us of all of the places in that person’s genome that differ from the reference. The reference is what’s considered the “normal”. What I’m looking for there are the rare variants – the ones that maybe only my patient has or maybe one or two other cases have. Those are the kinds of variants that I’m interested in. So, polymorphism which, by definition, is in more than one percent of the population, would be something I would filter out immediately and, instead, be looking for the very ultra-rare mutations. When we think about severe inherited diseases, we think about very rare mutations.
Michael: With all that information now at your fingertips, because that’s really what this is, right? It’s a database of a person’s genome. That is so much information there. What exactly, as a clinician, do you do with that and what are we able to do with that now and where’s this going in the future?
Dr. Soden: It really depends on the circumstances that brought the patient to testing and the circumstances around the initiation around that testing. What I mean by that is, we have some patients that we sequence because their physician ordered clinical testing, ordered diagnostic testing, and, in those cases, if the physician ordered the entire genome to be sequenced, all of the genes and the stuff in between, then we would require that a genetic counselor be a part of that ordering process and spend a sufficient amount of time with the family to find out, “Do you just want to know the answer or do you just want us to go looking for the cause of your child’s symptoms or do you also want us to give you some information back about risk factors?” So, if there’s a significant genetic change and a cancer predisposition gene, for example, there’s a certain list that clinical labs are expected to provide information back to families who want that. Then, the family has the opportunity to choose, do we or don’t we want that information. In those kinds of cases, we might be looking for the diagnosis and looking at some other genes. In other situations, and what we do a lot of here at Children’s Mercy is called “symptom driven testing”. In those cases, what we do is the sequencing is the same but the analytic process filters out all genes that have nothing to do with the patient’s symptoms. What we’re doing as an analyst and, it’s still a mass of data, just smaller, is that we’re just looking at those variants, those changes that are in or around genes that might have something to do with the patient’s symptoms. So, it really depends.
Michael: My guest is Dr. Sara Soden. She’s the Director of The Center for Pediatric Genomic Medicine at Children’s Mercy Kansas City. Dr. Soden, tell us a little bit more about the center that you direct, the professionals involved and where you see your center going in the future.
Dr. Soden: Sure. One of the things that really is just fun about being part of the center is that we have a very integrated research in clinical programs. The clinical testing that we offer all was developed under research protocols and we continue to perform a variety of different research protocols so that we can keep pushing the envelope. Just an example is one of the really cool things that our lab is working on right now is something called “single cell sequencing” which is a type of sequencing that really helps determine if there are different populations of genetic changes in different cells in the body. One tissue may be some cells that have one genetic code and other cells that have another. We’re always doing what we call “R&D”--research and development. That happens all of the time and it’s really fun and keeps it interesting for us. Then, at the same time, we’re able to take those technologies as they evolve and bring them to the clinical world so that physicians and patients who are a part of Children’s Mercy have access to the latest and greatest cutting edge testing.
Michael: Really, we’re at the cutting edge, aren’t we, or the tip of the iceberg with understanding the genome and exactly how to apply everything you’re doing in the lab to the clinical world. I think you’re right. It is exciting and it probably is a lot of fun for you. Dr. Soden, thank you for the work that you’re doing and thanks for coming on the show. You’re listening to the Transformational Pediatrics with Children’s Mercy Kansas City. For more information, you can go to childrensmercy.org. That’s childrensmercy.org. I’m Dr. Michael Smith. Thanks for listening.
Neurodevelopmental Disorders: Studying the Clinical Impact of Genomic Sequencing
Dr. Michael Smith (Host): Our topic today is “Neurodevelopmental Disorders – Studying the Clinical Impact of Genomic Sequencing”. My guest is Dr. Sara Soden. Dr. Soden is the Director of The Center for Pediatric Genomic Medicine at Children’s Mercy Kansas City. Dr. Soden, welcome to the show.
Dr. Sara Soden (Guest): Thank you for having me. It’s my pleasure.
Michael: How many kids in America are affected by neurodevelopmental disorders?
Dr. Soden: It really depends on how you define them. When we think about more severe neurodevelopmental disorders like intellectual disability or children who meet full criteria for autism, the number is probably around 3-4%. If we begin to think about individuals with milder disabilities, such as language disorder or even ADHD, then we get above 10% in terms of number.
Michael: I know what you’re focusing a lot now on is genomic sequencing. Why don’t we start off with what exactly is genomic sequencing and why is it so important, in your opinion?
Dr. Soden: Sure. As most of our listeners probably know, the Human Genome Project really transformed our understanding of gene sequencing and the human genome in general. For example, we thought there were maybe 30,000-50,000 genes. Now we know there are only about 20,000 genes that people have. So, even on a very fundamental level, some of our knowledge has changed dramatically. More importantly for medicine, what the human genome project began was this revolution in technology. Now we have the capability and in institutions like ours of sequencing a person’s genome or just their genes which we call the “exome” for a cost that is relatively comparable to other types of commonly used genetic testing. Now, when we have a patient who comes in with a set of symptoms and an unknown reason for those, we can perform what we call exome or genome sequencing and oftentimes get an answer for that family. In the past, individuals with rare diseases or hard to detect genetic diseases would sometimes go decades without an answer, which can be very difficult for a family and oftentimes never get an answer. We’re really changing that now. We’re able to give that family a reason for the symptoms that they’re dealing with and allow them to sort of get past the asking of why and move on towards just really focusing on the child and what they need to do to meet the child’s needs.
Michael: Dr. Soden, in the adult world, what we might do is look at something like depression or anxiety and we can discover polymorphisms that are common to that population of patients. Then we could look at somebody’s DNA, we can sequence it and look for those polymorphisms and let that patient know “you might be at an increased risk because you have that association”. How does it work exactly? How does genomic sequencing work exactly for children with neurological disorders?
Dr. Soden: What we’re really looking for is something quite different than what you’ve described which is a very sort of powerful tool as well but what we’re looking at are inherited diagnoses. For example, when I sit down in front of a variant file--and that means when we run someone’s exome or genome--we get a file that our bioinformatic tools give us of all of the places in that person’s genome that differ from the reference. The reference is what’s considered the “normal”. What I’m looking for there are the rare variants – the ones that maybe only my patient has or maybe one or two other cases have. Those are the kinds of variants that I’m interested in. So, polymorphism which, by definition, is in more than one percent of the population, would be something I would filter out immediately and, instead, be looking for the very ultra-rare mutations. When we think about severe inherited diseases, we think about very rare mutations.
Michael: With all that information now at your fingertips, because that’s really what this is, right? It’s a database of a person’s genome. That is so much information there. What exactly, as a clinician, do you do with that and what are we able to do with that now and where’s this going in the future?
Dr. Soden: It really depends on the circumstances that brought the patient to testing and the circumstances around the initiation around that testing. What I mean by that is, we have some patients that we sequence because their physician ordered clinical testing, ordered diagnostic testing, and, in those cases, if the physician ordered the entire genome to be sequenced, all of the genes and the stuff in between, then we would require that a genetic counselor be a part of that ordering process and spend a sufficient amount of time with the family to find out, “Do you just want to know the answer or do you just want us to go looking for the cause of your child’s symptoms or do you also want us to give you some information back about risk factors?” So, if there’s a significant genetic change and a cancer predisposition gene, for example, there’s a certain list that clinical labs are expected to provide information back to families who want that. Then, the family has the opportunity to choose, do we or don’t we want that information. In those kinds of cases, we might be looking for the diagnosis and looking at some other genes. In other situations, and what we do a lot of here at Children’s Mercy is called “symptom driven testing”. In those cases, what we do is the sequencing is the same but the analytic process filters out all genes that have nothing to do with the patient’s symptoms. What we’re doing as an analyst and, it’s still a mass of data, just smaller, is that we’re just looking at those variants, those changes that are in or around genes that might have something to do with the patient’s symptoms. So, it really depends.
Michael: My guest is Dr. Sara Soden. She’s the Director of The Center for Pediatric Genomic Medicine at Children’s Mercy Kansas City. Dr. Soden, tell us a little bit more about the center that you direct, the professionals involved and where you see your center going in the future.
Dr. Soden: Sure. One of the things that really is just fun about being part of the center is that we have a very integrated research in clinical programs. The clinical testing that we offer all was developed under research protocols and we continue to perform a variety of different research protocols so that we can keep pushing the envelope. Just an example is one of the really cool things that our lab is working on right now is something called “single cell sequencing” which is a type of sequencing that really helps determine if there are different populations of genetic changes in different cells in the body. One tissue may be some cells that have one genetic code and other cells that have another. We’re always doing what we call “R&D”--research and development. That happens all of the time and it’s really fun and keeps it interesting for us. Then, at the same time, we’re able to take those technologies as they evolve and bring them to the clinical world so that physicians and patients who are a part of Children’s Mercy have access to the latest and greatest cutting edge testing.
Michael: Really, we’re at the cutting edge, aren’t we, or the tip of the iceberg with understanding the genome and exactly how to apply everything you’re doing in the lab to the clinical world. I think you’re right. It is exciting and it probably is a lot of fun for you. Dr. Soden, thank you for the work that you’re doing and thanks for coming on the show. You’re listening to the Transformational Pediatrics with Children’s Mercy Kansas City. For more information, you can go to childrensmercy.org. That’s childrensmercy.org. I’m Dr. Michael Smith. Thanks for listening.