57 – Discussing SYNGAP1 Related Developmental Disorders

Here are our introductory comments:

Our presentation today is ‘Discussing Syngap1 Related Developmental Disorders’

I have the pleasure to introduce today’s speaker Dr. Holly Harris.

Dr. Harris is Assistant Professor of Pediatrics at Baylor College of Medicine and practicing physician at the Meyer Center for Developmental Pediatrics, a part of Texas Children’s Hospital, her in Houston.  She obtained her Bachelor of Science in Biology with a minor in Medical Humanities and Chemistry at Baylor University.  Proceeding this Dr. Harris received her Doctor of Medicine at Baylor College of Medicine in 2012.  She completed her residency in Pediatrics at Boston Children’s Hospital where she also received her Fellowship.

Dr. Harris has received many awards and she is committed to providing family-centered and evidence-based care for children with neurodevelopmental challenges.  Her research interests are in Autism Spectrum Disorder to include SYNGAP1.  Dr. Harris’ clinical interests include ASD, ID, ADHD, learning disabilities, anxiety, genetic and metabolic disorders, behavioral concerns and prematurity.

THIS IS A TRANSCRIPT ONLY:

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hello everyone and welcome to today’s webinar my name is olga Bothe and i’m a syngap parent and part of the team here at syngap research fund our presentation today is discussing SYNGAP1 related
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developmental disorders i have the pleasure to introduce today’s speaker dr holly harris
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dr harris is the assistant professor of pediatrics at baylor college of medicine and practicing physician at the meyer center for developmental pediatrics which is part of texas
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children’s hospital here in houston she obtained her bachelor of science in biology with a minor
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in medical humanities and chemistry at baylor university preceding this dr harris received her doctorate of medicine at baylor college of medicine in 2012 and she completed her
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residency in pediatrics at boston children’s hospital where she also received a fellowship
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dr harris has received many awards and she’s committed to providing family-centered and evidence-based care for children with neurodevelopmental challenges
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her research interests are in autism spectrum disorder to include SYNGAP1 dr harris clinical
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interests include autism spectrum disorder intellectual disability adhd learning disabilities
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anxiety genetic and metabolic disorders behavioral concerns and prematurity a recorded version of
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this webinar will be available on the syngap research fund website under the resource tab
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and by the end of this presentation you’ll have the opportunity to get the answer to your questions and we’d love to hear from you so please write your questions in the Q&A below
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for those of us just joining us welcome and again our speaker today is dr holly harris discussing
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SYNGAP1 developmental related disorders it’s now my pleasure to turn things over to dr harris
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all right well it is really a pleasure to be here let me go ahead and share my screen so that i’ll
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have my slides up there everyone can you see that i can get a nod from yes all right perfect okay
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so yeah like i said it’s an honor to have the opportunity to speak to you all and hopefully you’ll find this information useful and i do hope to leave plenty of time for questions so
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if i don’t cover your particular question during the talk there will be plenty of time for that
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at the end all right so my learning objectives are for you to understand the range of potential
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developmental outcomes for individual with individuals with SYNGAP1 mutations to understand
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the definitions of autism and intellectual disability and the overlap and distinction between the two and to know some of the optimal therapeutic and educational interventions for
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these developmental conditions and so i’m gonna move my screen around just a second okay perfect
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so i wanted to start right off the bat with what we do know about SYNGAP1 related
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developmental diagnoses and a lot of this comes from cases that have been
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reported in the literature and that have been described thus far so whenever we as clinicians
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learn about a new genetic finding that might have implications on medical or developmental outcomes
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then we start to try to kind of gather that information collectively and as soon as we find several individuals who have a genetic diagnosis and we see kind of what it’s how it’s impacting
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their neurodevelopment then we’ll try to put that out there in the literature via case report so some of you may have even gotten to you know
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i think okay i think we’re good some of you may have even gotten to read some of those or that’s where you kind of first learned about what to expect but what we do know from what has been
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published thus far is that intellectual disability is pretty universal i think a lot of the rates
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that i’ve seen at about 96 percent and epilepsy as well and those are usually myoclonic seizures
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absence seizures and the like and then there are a proportion of individuals with SYNGAP1 mutations
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that will have autism usually ranging from about half to 75 depending on kind of what what study or
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what case series that you’re looking at and then ataxia unsteady gait that’s another very common
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feature a few distinct behavior difficulties particularly some risk of aggression and perhaps
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self self-injury in some individuals a lot of impulsivity and then sleep challenges as
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well and i’ll also say that we have realized that there are some significant differences
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in sensory processing so how the individual processes sensory information either is very
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overstimulated by sensory information or sometimes hyposensitive so things that would bother
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someone like pain or something like that may not be as easily perceived in SYNGAP1 mutations
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and so i wanted to go into this in a little more detail based on individuals at our center so i work at texas children’s hospital with dr jimmy holder who does a lot of work
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in SYNGAP1 and there was a report in 2019 it’s there at the bottom the author’s name was
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dr jimenez gomez but it went through 15 cases that have been seen at texas children’s hospital and
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kind of i’m going to give you an overall synopsis of that so what we learned is that the average age
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at diagnosis well really i shouldn’t say the average age what i should say is that the the agent diagnosis had a huge range so some children were recognized before three years
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but then there were some individuals that their SYNGAP1 mutation wasn’t found until about 14 and a half years of age we did see that there is what we would describe as a
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plateauing of development around five years of age and doesn’t mean that a child can’t learn new skills but i think we do see that in terms of kind of making large gains in developmental
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skills whether that’s speech and language motor gross voter fine motor adaptive skills that
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kind of do hit a bit of a plateau after age age five but the timing of when children would gain
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certain skills was also variable in our population and so what i mean by that is
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if you actually go and kind of look at the paper there’s a wide range of some children gained these
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skills much earlier than that the average that i’m reporting here and some it took much longer but
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on average the first word was around three years of age children sat around 10 months of age
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and walked around 24 months of age scribbling and use of utensils so the ability to use one’s fine
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motor skills and hands usually that was a bit longer before that skill was acquired so maybe
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four around four years of age and again these are kind of just the mean based on those 15 cases
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and we also saw that overall all individuals had moderate severe or profound intellectual disability although there was one individual in our case series that had mild intellectual
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disability which was a bit unusual compared to what what is seen kind of on the broader scale
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i did talk to dr holder about this a little bit because i was curious if he thought that there were you know certain aspects of the mutation that could kind of help us predict
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children that might not have as severe cognitive deficits and he really
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couldn’t give me a straightforward answer he said not you know not especially there are some mutations at the five prime edge or splice site variants that can maybe indicate that
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there may be a milder presentation but he was like he’s like up until this point i haven’t kind of seen any hard and fast rules around that and so i also listed here kind of the
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highest skill that was described for some of these children so for gross motor skills you
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know walking up and down stairs and jumping fine motor skills kind of feeding oneself with utensils
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expressive language so what we’re actually able to say or communicate whether that be speech signs
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several children have had five to six signs others some children had two to three word sentences
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and the vocabulary ranged you know everywhere between one to 250 words and receptively kind
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of the maximum level i saw described was one to two step commands and again this was kind of based on the notes that already existed within our within our medical records here so
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i think one other thing i’ll mention here and that someone kind of was inquiring even before the talk began is are there are there things that can hint us to SYNGAP1 mutation early so what can
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we be looking for as clinicians or as parents to kind of let us know that perhaps we need to
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do testing for up for a SYNGAP1 mutation and it is it’s still challenging to say i will say that
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kind of i’m going back to this slide here because you can see that in general for a lot of our kind
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of developmental milestones children with SYNGAP1 mutations are taking about twice as long to meet
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that milestone or even or even longer so a first word we think about it around a year and so the
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mean age was around three years sitting we think about it six months it’s you know it’s almost
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double that before the child is reaching that milestone some of the first milestones that you
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see or that parents can recognize are those gross motor milestones like sitting and walking and so
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if you already are seeing delays in that in that the child is six months and really not sitting has
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a low tone that to me is definitely an indication to think more of a genetic metabolic workup
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and so you know standards for us as clinicians are chromosomal microarray and fragile x testing so
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sometimes that doesn’t always pick up more specific genetic diagnoses and so
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i think we are getting better about maybe even moving toward whole exome sequencing or other
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panels where we include certain genes so perhaps SYNGAP1 would be included within a a genetic
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testing panel that we send for kid for kids who have these kind of prominent gross motor
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delays at a very early age i would say in all of my reading and the patients that i have had the chance to see thus far some of those other distinctions are really the ataxia
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and unsteady gait component and that the epilepsy and the type of seizures that are seen i’m not
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a neurologist but i do get the sense that there’s kind of a characteristic type of seizure that may those may be other hints toward leading one to test specifically for SYNGAP1
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okay and i as a developmental pediatrician i often get the question why do some but not all children
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with SYNGAP1 mutations have autism or kind of other developmental behavioral diagnoses
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like adhd so some children might have been given those diagnoses and others may not have
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those diagnoses and so why is that if they all share the same genetic diagnosis and the answer to that is because genetic diagnoses and developmental
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diagnoses are different and what i mean by that is a genetic diagnosis is based on highly
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accurate laboratory genetic testing so we have an answer on paper written down kind of exactly where
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you know the gene has been edited or or deleted and it gives an etiology or a reason for a child’s
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presentation and it can also alert us to potential medical or developmental findings in the future
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whereas developmental diagnose a developmental diagnosis is not diagnosed using blood tests
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or brain imaging which i think contributes to a lot of the kind of gray area around
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some of these diagnoses because we can’t kind of go back to an objective blood or
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imaging test to tell us whether or not a child has a developmental diagnosis rather these are quote clinical diagnoses because they’re diagnosed by professionals or clinicians
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based on the child’s developmental history so what we learn from you as parent or caregiver and observe behaviors that we see during the visit so depending on how long the visit was or what’s
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going on you know you can see how you may or may not see certain behaviors within a visit
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and the symptom criteria for these diagnoses are described in this picture of this book i have here the diagnostic and statistical manual mental disorders fifth edition so you can see
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there’s another layer there because it’s the fifth edition so that means there’s been four other editions before and so these definitions are even getting revised over time so it can be quite
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confusing when it comes to developmental diagnoses so genetic and developmental diagnosis are related
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but not the same a genetic diagnosis often doesn’t tell us what specific developmental and behavioral
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symptoms the child has or will develop like i was saying earlier you know dr holder said
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i still can’t really make predictions based on what i know about the genetic finding and kind of where it is as to what the ultimate developmental outcomes will be for any given child
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and so i want to talk some more about definitions and how do we actually make these developmental diagnoses since that is my area of expertise in all of this
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so i’ll start with intellectual disability and how it’s defined in the dsm-5 as pretty much the major
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vast majority of individuals with singapore mutations will have intellectual disability so this is defined as number one deficits and intellectual functions which just means
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there are challenges with reasoning problem solving planning judgment learning and that
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results in deficits in adaptive function so that is defined as an inability to meet developmental
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and social sociocultural standards for personal independence and social responsibility
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so okay dr harris you’ve given us a definition but how is that that’s how it’s defined but what does that actually mean and how is it diagnosed
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so for the first point deficit and intellectual functions generally translates into performance
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kind of in two standard deviations below the mean so if 100 is kind of the average mean
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for the population an intellectual quotient or an IQ of below then below 70 would be in
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the range of intellectual disability so how is that measured it should be measured with
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an individualized standardized culturally appropriate psychometrically sound measure and so
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the that’s a lot of words in there but those tests are often administered by a psychologist either at
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an outpatient facility or in the school setting a brief version of one of these measures can be
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administered by a clinician such as myself a developmental pediatrician or a neurologist and so if you come to our clinic at texas children’s i’m usually doing this one here the
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cat clams on the left and this middle one is called the stanford binet it’s a common one used
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by psychologists and that’s a little more like intense and in-depth but as you can see there’s
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a lot of limitations to these types of measures so what about children who do have fine motor gross
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motor difficulties and you know you’re asking them to manipulate small objects or maybe they
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don’t use spoken language so those types those components of testing don’t seem as relevant so
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we are getting better at trying to tailor these types of measures to different populations but
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it’s still definitely not a perfect science there are some tests that are completely non-verbal so
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it removes the language component and you’re still trying to assess problem solving without needing
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to rely on expressive language but there are other factors that go in like did your child sleep the
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night before and how are they feeling that day and are they comfortable with the examiner so
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these types of tests give us a number that’s like one point in time but it can be useful to give a
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baseline to and you know to see where things currently are and and where to go from there
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so that’s point one of that definition and then two would would be adaptive functioning and the
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severity of one’s intellectual disability is actually determined by this part by the adaptive functioning so you know you may score at a certain level on an iq testing measure but what
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does that actually mean in your day-to-day life and and that’s what we actually use to determine how severe it may be how much is it impacting the child’s ability to care for themselves
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in any way so this is assessed by measures such as the ones kind of listed here as examples so
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you as parents or caregivers may have filled it on an abass or a vineland and it goes through all those different areas and so we rely on parent or caregiver to tell us kind of in the day-to-day
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what is the individual able to do and and how are they functioning and then you can see here kind of
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it’s still that 70 or below is still kind of the when it falls into the intellectual disability
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category and you can see how it’s broken down mild moderate severe and profound from there
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okay there were a few other clarifying points i wanted to make about intellectual disability one is that you may hear clinicians say cognitive delay or difficulty in
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cognitive functioning and really all of those are ways of describing intellectual disability
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and intellectual disability or id is invariably accompanied by delays in speech and language
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fine motor skills and gross motor skills relative to age because if you think about it
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a process that affects the entire brain in neurobiology such as the SYNGAP1 mutation
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is going to affect you know everything broadly so you’re going to see delays in all of those areas because it’s all because the process is affecting the whole the whole brain
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and so i also wanted to touch a little bit on what can what can one expect so practically speaking
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when you know we give one of these designations for intellectual disability what does that
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actually mean for the individual and i’ll preface this by saying we make generalizations based on
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kind of over time what we’ve seen and learned from individuals who fall in these different ranges but
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none of it is hard and fast each child is unique children surprise me all the time so i always
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tell parents these are just guidelines we want to give you some clarity and kind of
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what to expect and don’t want to i want to be honest about that from what we do know but also
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realizing that we don’t always know all the details and so every child like i said always always has the capacity to surprise us but if if an individual
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is has profound intellectual disability we think about that individual functioning around
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three years of age and so we usually recognize that recognize profound intellectual disability
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well before two years of age because the delays are very prominent and very early similarly with severe intellectual disability we think about ultimate functioning
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at around three to five years and that’s usually recognized again before before age
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three moderate intellectual disability individuals function around six to eight years on average
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and we usually can recognize moderate intellectual disability between three to five years of age it’s
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a little bit it’s not quite as prominent so it takes a little bit longer sometimes for
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teachers parents doctors to recognize that there might be a delay and then mild intellectual
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disability a lot of individuals in the community have mild intellectual disability and it may never be formally recognized or if it is it may it’s usually after age five or six
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and when the child is in grade school and may be having some academic struggles i mean ultimately
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those with mild id can be fourth to fifth grade level in terms of reading basic arithmetic
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writing filling out a basic job application things like that so i did want to touch on that because i
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think a lot of times we use terms and parents want to know you know what don’t really know
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okay what are you actually saying with that and when what should i expect and how do i you know convey information to my child and also not that it gets hard to think about these things
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i think it can be helpful because if you know okay my child is more in a certain age range it will
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change both maybe how you communicate or kind of how you teach them because it can help reframe and
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teaching them at their level is extremely important for them taking them to the next level
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because i was discussing this with the family the other day that it doesn’t mean that the child
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will never get you know the child will never learn new things because anyone can learn new things it
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just might take a lot more practice or might take saying it in simpler terms and that’s where kind
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of knowing these expectations can really help us help children to achieve their maximum potential
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and so lastly a word about the term global developmental delay it’s something else you will hear kind of in this journey clinicians often use it for younger children who have delays
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in all domains of development so global meaning it’s speech fine motor gross motor problem solving
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and we tend to use this term in younger children because it’s really hard to make a determination
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or about intellectual disability until a little bit later because that early time frame is such
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a time period for rapid growth and change that we’re not comfortable like committing to anything
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for a while in terms of of what to expect so global developmental delay is used in younger children it can potentially signal that a child will go on to have intellectual disability
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not always but a lot of times it’s for us as clinicians when we see that you know we’re thinking oh this child may this child may have intellectual disability in the future
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okay i’m gonna check my okay timing so because now we’re gonna move on to talk a little bit about autism and how it is defined in the dsm-5 so autism is separate from intellectual disability
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and i think that in and of itself can be confusing sometimes autism just talks about difficulties in two areas you’ll hear them called criteria because that’s how this
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book describes it so there’s social communication deficits or difficulties and those are the a
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criteria and then restricted and repetitive behaviors and those are the b criteria
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so for a child to have autism you have to meet all of these a criteria so one is deficits and
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social emotional reciprocity so kind of that back and forth exchange people say you know back and
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forth conversation well for a child who doesn’t use conversation that’s even things like you know a parent does peek-a-boo the child responds so it’s that kind of back and forth with a parent or
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friend or caregiver and then the second is deficits in nonverbal communication so those
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are things we ask about like eye contact and do they point or are they trying to use other means
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to communicate with you and then the third is difficulties in developing and maintaining and
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understanding relationships so what does that look like for a child with delays it can be just as simple as just preferring isolation and not other individuals or we often look at how a
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child plays in order to give us an understanding of relationships that’s how that’s how it’s
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manifested in early childhood is through play so seeing if they kind of play in a creative way or
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do they really just become centered on an object and not so much people around them so you need all
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three of those and then two out of these four for the behavior so those are things like repetitive
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motor movements or speech insistence the second one is insistence on sameness or inflexibility
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this is where people ask about do they have trouble with transitions many young children do
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have trouble with transitions anytime we’re talking about autism we’re thinking okay is this above and beyond what we would expect for a child this age and then the third is highly
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restricted or fixated interest that are really abnormal in their intensity they really can’t be
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moved away from one given thing and the last is this hyper or hypo reactivity the sensory input
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and so you can see how autism gets confusing because it is just defined by these behaviors
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that are determined by a clinician based on what parents tell us and what we see of the child so all three of those eight criteria on the left and then two out of the four of these
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a lot of times in genetic disorders such as SYNGAP1 mutations
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clinicians will kind of use this term autistic features and so when i hear that i often take
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it to mean that the child doesn’t necessarily fit all the hard and fast criteria for autism
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but does have some of those symptoms just maybe not kind of the full picture i think a little bit
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of a tangent to that is that that can be really challenging actually because sometimes if the
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child doesn’t meet the full autism criteria and so therefore there’s not a diagnosis of autism that can sometimes impact access to therapies which is unfortunate and should not be the case
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but i did want to present this information because i think it can be confusing to family members caregivers providers that why do some children have autism and some don’t a lot of
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times it’s dependent on the clinician or just the day that they were seen in clinic or the report of
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these symptoms because it is just defined by those things and many children with SYNGAP1 mutations
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from what i’ve gotten to see so far clinically and from what i read have a lot of these features
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i mean obviously there’s going to be social communication deficits we know that sensory
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differences in how they process sensory information is a feature that we’ve seen in fact one of our clinicians here did a whole study kind of the patterns
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of sensory processing and syngap so we know that that’s there so anyway i wanted to kind
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of touch on that and i’m sure there may be questions and we can we can talk about that
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because and this is another another thing that comes up a lot autism and intellectual disability
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it can be confusing because some some children have one some have both and you can see how those symptoms overlap between the two like i was just mentioning delays in communication
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repetitive or stereotype movements can be seen in both of these diagnosis diagnoses sensory behaviors other behavioral challenges and attention hyperactivity
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aggression can be seen in either or both of these diagnoses adaptive and learning challenges and
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difficulties in making same age friends is going to be kind of a part of both of those
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i won’t really belabor this point just for the sake of time but we can go back to it if those are interested there are certain things that i as a developmental pediatrician can look at to try
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to tease out these two but i’ll say that maybe for questions and then there’s there’s this big bucket
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of quote behavioral difficulties so examples like inattention hyperactivity aggression self-injury
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impulsivity eloping and that means running out of the room and physicians tend to like to categorize
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things under you know diagnostic labels so we may characterize it by using a given term attention
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deficit hyperactivity disorder adhd usually that means inattention hyperactivity impulsivity
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some might say i think this is because of anxiety so i’m going to use the word anxiety to describe these behavior difficulties or there’s something called disruptive
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mood dysregulation disorder which is kind of a catch-all term for some of these challenges
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but i like to do to just put that out there because i think it’s another confusing area where you know you’re like why are some children labeled as having adhd and others
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don’t sometimes it’s just how we’re trying to describe a behavior that a behavior that we see
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okay i was gonna take a question break but maybe i’ll just plow through and then just leave a lot
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of time at the end i know because i wanted to touch really quickly on what we can do to help
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right because i think that’s one of another huge thing that we’re seeking out of these
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talks and i think it’s incredible that you guys have this collective group that’s interested in
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SYNGAP1 mutations because this is what’s going to foster you know how do we gain the knowledge
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and disseminate it quickly and then how do we figure out what is the best way to help these
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individuals so when it comes to intellectual disability or global developmental delay
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our best support is therapeutic services so speech therapy that to target speech and language delays
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and in SYNGAP1 along with many genetic diagnoses it’s really critical that this involves some
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form of augmentative communication which is just our fancy way of saying something other
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than just verbal speech because verbal speech is going to be difficult so we need pictures we need
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some type of maybe a device or even just simple communication buttons off of
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amazon where you can put your voice on them and that gives your child a way to communicate a choice because that’s really going to be critical over time and one of the
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best things we can do is give our children a way to communicate with the world so you always want
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to make sure if possible your speech therapy has some type of augmentative communication
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occupational therapy that’s going to address hand use adaptive skills toileting daily living skills and then physical therapy is going to work on the balance the core strength the
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mobility the hypotonia and these hopefully can be found as an outpatient and what i mean by that is
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you know in addition to what you’re getting at school maybe you take your child to a center maybe the therapist comes to your home and i always encourage families do as many sessions as
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your child and your pocketbook and your time can tolerate because all those things factor in
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and at the end of the day your child will let you know you know how much therapy he or she can take and it’s really all a balance between what is what is most helpful to your
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child and most meaningful to your family it’s not about running yourself ragged trying to get to
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all these services sometimes more time doesn’t equal more gain gains and so i always like to
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make sure that parents know that you parents and caregivers know that you know your child
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the best and you’re the expert and you’re the best advocate so trust yourself and your decisions and
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yeah don’t don’t second-guess yourself trust trust what you know to be true for your child
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your family your time what you’re able to to do in that moment you know we do think the more and
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the earlier we can do these services the better so just something to take away there and then
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also you want to make sure the child has an individualized education program or an IEP special education services through their school system the school should be delivering speech
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ot pt as part of the IEP so that’s something else that you would want to see and expect
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and there are behavioral therapies that can be very helpful ABA it stands for applied behavioral
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analysis is a type of behavior therapy that has a large evidence-based research evidence base
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for improving daily living skills and cognitive skills when it’s given in high intensity and at
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young ages that’s kind of and in autism so that’s where all the research has been done
33:14
which is a little in some ways unfortunate because then that translates to you know because all the
33:19
research is in autism if you don’t have autism it’s hard to access that therapy which shouldn’t
33:24
be the case we also know that this therapy helps with intellectual and intellectual disability it helps children build adaptive and cognitive skills so it should work for any child
33:35
but and even even if the child does have an autism diagnosis it’s still hard to find because of
33:40
this need far outweighs the supply of available providers so i’ll also say that there are
33:49
a lot of very varied opinions around aba and many individuals with autism who are verbal and who can
33:56
speak will say that they maybe feel it’s too rigid or too kind of the basic form of aba is called
34:02
discrete trials and they feel like it’s yeah i guess again too rigid and not not flexible enough
34:10
so a lot of times depending on the therapist or the way the therapy was delivered it can impact
34:17
people’s view of the therapy as a clinician i will say that we have found it can be very effective in
34:23
helping with difficult behaviors and sometimes it isn’t a great fit for the therapist so again
34:28
you’re your child’s best advocate so if you feel like something’s not right here definitely listen
34:34
to that and talk to your clinicians about it and figure out a way to find an effective provider
34:41
essentially ABA teaches parents
34:47
more detail about how to figure out the function of the behavior so why is the behavior happening
34:52
because that’s really going to inform everything so then what do we do to help reduce the behavior or what do we do to help build a behavior that’s why it’s
35:00
called applied analysis so a lot of the therapy initially is spent just understanding the child
35:06
watching the child seeing what kind of triggers these behaviors and how do we respond that
35:12
maybe we’re accidentally keeping that behavior going or what do we need to do to change it
35:17
because aba is hard to find i mentioned parent management training here because sometimes that can be more easily accessed and it uses a lot of the same principles about how to build
35:27
skills and how to reduce problematic behaviors by building positive behaviors
35:34
and i think my biggest quick tips for parents is to at first always consider communication so so many times the behavior is related to
35:42
difficulties in communication and so it’s just the child’s way of trying to communicate something and then think about these other reasons maybe sensory maybe they’re sensory overloaded or they’re bored
35:53
or maybe you know giving them something else to do with their hands might just completely distract from the behavior it could be pain i know as clinicians we think a lot about could this be
36:02
constipation or dental pain and maybe the child doesn’t know how to tell us what’s going on uh oftentimes it’s just to obtain something that they want or to get out of something they don’t
36:11
want to do and in those instances it’s hard because the answer is to stand strong and not
36:16
you know not allow the behavior to get the desired goal and some are just automatically reinforced
36:24
and those are the hardest that’s where we really rely on our aba therapists to help because that just means that we don’t we can’t figure out why it’s happening and it clearly serves
36:34
a function for the child but but we don’t know what that is and so we don’t know how to help that and that’s where behavior therapists really will get down to some very specific analysis
36:47
and i just just to say explicitly that obviously it’s important to remember cultural considerations
36:53
and your family context because that informs our expectations and practices and how we interpret
36:58
behaviors and how we respond to them okay and a few last thoughts therapeutic and educational
37:05
interventions should always particularly when we’re thinking about individuals assisting gap 1 or individuals with intellectual disability should always focus on functional adaptive skills and
37:13
improving independence in your day-to-day life you know it’s not like while it’s great to do
37:19
counting and things like that like sometimes it’s better to focus our time on on functional skills that are going to help us communicate in the world and be yeah be more independent in
37:30
the day-to-day functions uh i already mentioned some of the issues with access access can be a huge challenge for any of these therapies again i want to reinforce that augmentative communication
37:39
is very key and that last point practice practice practice i think something that is both probably
37:47
encouraging and also overwhelming is that you will have to reinforce the skill day after day
37:53
teach something again and again and it may feel like i’ve done this a lot of times but because of those cognitive delays it’s going to require a lot more reinforcement for a lot of these skills
38:04
i remember speaking with dr vincent who’s a neurodevelopmentalist who’s worked a long time with singaporean patients here she’s about to retire but she her thing her saying was always
38:13
to if you’re trying to teach something do teach it again day after day every day until the child
38:19
has mastered it for a long period of time and then you then you can finally stop teaching that that
38:27
particular skill and so ideally all the therapies and educational interventions will come first but
38:33
obviously there are medical interventions that we can do medications for some of these behavioral challenges that is a whole another probably lecturing of itself it’s confusing i feel like
38:43
a lot of times for parents i’m sure this feels like trial and error because there’s a lot of types of medications we can try for adhd-like symptoms impulsivity aggression and attention
38:54
and each child is very unique and different even medications that work the same way theoretically
39:01
one of them might work for a child and then i’ll switch if it doesn’t i’ll switch to a different one that technically works the same way and um that one might just be you know the magic bullet
39:12
for that child so like i said a whole nother lecture in itself but i’m sure it feels sometimes
39:18
can feel frustrating because sometimes we have to do a little bit of trial and error my one rule for medications is never change more than one thing at one time because then you don’t
39:27
might not know which thing helped or or hurt
39:32
and rely on your resources i know folks are listening from all over so i’m in texas but i try
39:38
not to list a lot of texas specific things but i mean this foundation and of itself like i said is
39:43
phenomenal um a lot of states have waiver programs where you know families can qualify for services
39:53
that you know you know it’s irrespective of income that’s why they’re called waivers just if your
39:59
child has high needs there are programs that can give you support you just have to ask about them in your individual state easter seals in the arc i think are pretty are not just in texas
40:10
they’re they’re more broad organizations and they can be really helpful of knowing your local
40:15
like therapies and resources and your local intellectual disability agencies
40:20
you can google litta in your area and then there’s a lot of info out there in terms of
40:28
syngap1 specifics if you’re interested in some of the more specifics around the findings and
40:34
both medical and developmental and uh there are places to find that and i think i will stop here
40:43
a little bit over time i know for the goal but um stop here for questions i can go back to anything as well that was great thank you i really appreciate it we’ve got um
40:55
a few of us here in zoom and i’ve i’m watching facebook there’s five or six out there so for the facebook folks if you want to use the short link syngap dot fun slash um
41:05
was it holly or was it harris i think it’s holly it’s in the link um you guys can join and ask questions live i have a i have a bunch of questions dr harris
41:16
where to begin so let’s start with so i appreciated you talking about the id
41:22
um because i mean almost all of our patients have that um except for those with who are mild which
41:29
you pointed out there’s one in dr holder’s set who is oddly mild i’m very familiar with that case um
41:38
i will observe that within our patient population we have a couple the five prime is the beginning
41:43
and the three prime is the end is that right yes yeah so so it in the vlasscamp 2019 paper
41:48
they observed that mutations in exon one through five so the five prime are generally a milder phenotype and we have identified the three three three dells c three three
41:57
del and as a 192 del so people with deletions really early on seem to have milder phenotype
42:05
and then the case in um jimmy’s data set is c3583-9 so that’s an intronic over by exon 19.
42:14
so really that the takeaway there is any mutants that are in the ends where you start getting into
42:19
isoforms seem to be milder broad observation not yet backed up by science there’s a fellow at um
42:27
boston children’s hospital right now analyzing the citizen data who will hopefully be able to validate these hypotheses um with the 170 plus patients we have in citizens so so that that’s
42:39
just i just wanted to mention that and then to come to the autism you mentioned 53 and 73 and
42:46
i think the 50 number comes from the blast camp 2019 paper which was an international cohort
42:52
and the 70-ish percent number comes from the jimenez gomez paper which was i think primarily
42:57
a u.s cohort right and and i think i’ve always that’s always struck me right there’s two things
43:05
there if i characterize those two populations the vast camp population was an earlier population
43:10
right it was more of ingrid’s work more global and it was more global earlier in global whereas in menos gomes more recent more u.s so it’s it’s it’s safe to say that wow the number was much higher
43:24
in in a more recent population and a u.s population right and i think in the us
43:30
agreeing with everything you said the cold hard reality is you can’t get access to aba or
43:36
countless other services or waivers or forgive the expression damn near any support in the absence of
43:43
an autism diagnosis so in the u.s people have had to um parents have had to work really hard
43:52
in conference in two short meetings with well-trained clinicians like yourself to navigate that a b check box rubric and get all the buzzwords yep to get that diagnosis and
44:07
i met so i really appreciated how you broke that down but here’s the question now speech complete
44:14
when i when i’m talking to singap parents going into those meetings i literally tell them give your child two snickers bars three red bulls kick him in the butt don’t let them sleep the night
44:22
before like just the goal is property damage right send it into that room and destroy the building
44:29
like make it so the clinician cannot possibly not give you an autism diagnosis but but the reason
44:36
but to be a little more serious i do say that but to be a little more serious
44:42
what i’ve observed in singap is the phenotype is broad and takes time to set in and the trouble with a three to five year old singapian is they still give everybody the
44:51
parents included a false sense of security so they walk into that clinician’s office they look you dead in the eye they’ve seen this movie before it’s like their 20th appointment
45:00
and they see dr harris and they smile because they know that’s how they’re going to get out of this room right and it’s not going to be until they’re four five six seven eight
45:10
that their elopement and their aggression and their fixations become more pronounced
45:17
so what i hear parents say is the person who they come to when they’re at the wit’s end is i went to
45:23
get the autism diagnosis the doctor disqualified me because the first thing the kid did was smile
45:29
at them and they were like this kid’s not autistic which i think is too simple and and sort of over indexes on eye contact yeah but then what i say to them is go back and fight harder because
45:40
the presentation has evolved right yes how would so the question is like how
45:46
does a parent re-engage the developmental pediatrician or the pete or the whomever
45:52
to make that argument look the the phenotype like what are the buzzwords they need to use
45:57
yeah to to get that reassessed yeah oh that’s a great question i think
46:05
i think it’s very challenging because i think even within you know primary care pediatrics i mean i
46:12
think about even as we are educating learners that are going out to be primary care pediatricians
46:18
autism is still there’s still this sense of like oh if the child smiled or looked at me
46:24
in the eye they don’t have autism which that’s not the case just like you were saying like in general for any child um there’s a lot more subtlety to it i think i think your point of
46:36
going back and fighting harder is a good one sometimes depending on where you are
46:42
depending on the clinician and how maybe for lack of better terms um rigid they are about certain
46:49
things um you may be i mean it may be worth getting an outside opinion i think a lot of us
46:59
because these are just these descriptive diagnoses um a lot of us like you’re pointing out i think of it as autism is this big umbrella and there are genetic syndromic forms of autism
47:14
where like you were saying like children with singapore mutations have these features that
47:20
are part of the criteria and we because of the way things are it is unfortunate a disservice to maybe
47:28
not just acknowledge that from an early age um but as far as like if you’re not seeing some you know
47:35
someone who understands kind of the that whole spectrum like what to say or what to do i i mean
47:42
i think one part is just showing that knowledge like um speaking to others in the foundation who
47:48
have walked that road um going in there i think if you go in as a parent and you say like look i know
47:54
what autism is and let me tell you how they meet this criteria from my standpoint you know i think
48:00
in some ways maybe maybe that’s that’s the best way it’s kind of looking in the dsm-5 and um
48:08
because if you go into a provider with that level of knowledge and you’re able to get examples
48:13
from your child um in the home setting because it should be based on history and observations we’re
48:19
not going to see everything in two hours so that would probably be my my biggest piece of advice is to know that criteria and um especially like you’re saying i think the the sensory the behavior
48:31
side is more obvious but the social side can get you know confusing because someone might um might
48:41
smile at you once or whatever so if they can really articulate where those deficits are
48:46
in social you know back and forth um and i’m you know you would think it would be clear but i i
48:54
think if they can maybe argue in that perspective that might be helpful but um yeah it’s a great
48:59
question okay next question let me keep coming you said something that woke me up you said you
49:07
know our standard is cma for fragile x and the reason that makes me crazy dna and fragile x
49:17
because our kids tend to present like fragile x and a chromosomal microarray will not catch a syngap mutation correct yeah right so that’s
49:26
time wasted and as of a year ago and i i i must have misunderstood what you said then because
49:32
as of a year ago the acmg was like first line testing for kids with id under 18 should be
49:38
exome or genome so like i but literally the vast majority of our kids get get waste time and money
49:46
getting a chromosomal microarray and unfortunately many people are told when that comes back negative it’s not genetic which is just like right generally by older clinicians you’re recently
49:55
trained at exceptional institutions so i’m sure you would never say that but it kills me when why are we doing why are we even doing cma anymore why aren’t we just punting it right to x-woman genome
50:07
is one question and then i wanted to share this with you i recently spoke to um let me share my screen for a second i recently spoke to uh gene dx so this is a slide i put up at the gene dx
50:16
all staff and based on our first 90s patients in citizen here are my top sources of diagnosis right
50:25
so so gdx by far by a mile with 33 is a third of my diagnoses right in vitae
50:32
coming in second with 21. but there you are baylor at 13. um but when you double click on
50:39
this and i i didn’t have room for the baylor data eight of those 13 are whole exome trios
50:45
right it’s it’s it’s it’s at the and and and gene and you know vitae is more of the panel
50:53
um but i’ll tell you from from side conversations with them and vitae has two buses for every hit
50:59
and gdx has one bus for every hit i actually don’t know the baylor numbers i should find them out and i think that’s because the vitae system is you know it’s a panel it’s more automated it’s it’s a
51:09
yeah it’s quicker to bust someone yeah but my point here is
51:17
isn’t is i guess i’m asking isn’t the standard of care like when you just said we do cma and fragile x i was like no no we but we shouldn’t we should be doing
51:24
excellent genome or at least a panel right i just want to make sure i heard that writer um
51:30
unfortunately you did because i think and then your question is why so i agree with you based on
51:37
the most recent publications the most literature you read recently whole exome we should be doing
51:43
whole exome on autism idiopathic autism we should be doing whole exam on any you know anything we should be doing whole egg zone um but the insurance companies do not agree
51:53
um and so a lot of times what is out there in literature lags behind the widespread uptake um
52:00
amongst clinicians i think because we when you feel the luxury of being in a larger institution
52:06
um many times i will just refer my patients directly to genetics because they have in vitae
52:13
relationships with mbta panels they have saliva testing within the department they are able to um
52:21
better advocate for authorization um they are able to but still many times they will start with cma
52:27
and fragile x um and then once those are negative only then can they advocate for the whole exome
52:34
and the parents not have to pay out of pocket so sometimes it’s a function of that and in
52:41
addition to the genetics organizations like the american academy of neurology and the
52:46
american american academy of pediatrics like their statements still do not i think say whole exome um
52:53
so it’s a lot of people just wait for everyone to be on the same page um i do think i’m fortunate to
52:59
be at baylor where there’s a very strong genetics yeah no absolutely i love it and i mean if
53:05
insurance doesn’t cover if the child has seizures right if insurance doesn’t cover it behind the seizure would cover the envy panel exactly exactly so then get that right exactly so there are ways
53:15
that we should be able to get around that and yeah with especially if there’s other some other type of medical finding seizures even if i can argue um for some type of you know polydactyly
53:26
or some other quote unquote syndromic medical finding then sometimes we have more success
53:32
well i would i would also say we have we have two we have a partner in ambit and and also another one coming online soon who we can send someone to them and they will do free testing so
53:41
even if for whatever reason behind the seizure is not an option call us because yeah yeah i hate chromosomal microarrays i hate
53:49
uh almost as much they can’t stand insurance companies okay so we talked about that we talked about repetitive behavior dmd oh you you mentioned meds and i don’t want to try to get you on the
53:59
record talking about meds because i realize that makes doctors very nervous and i actually don’t
54:05
prescribe a lot either because i’m a developmental behavioral i do but anyway go ahead i’ll i’ll try my best but i then i guess you so when you when you suspect i guess that’s a two-part question the
54:16
first is when you suspect a child needs meds you refer to psychiatry no no i do start i do start
54:22
good so then because the thing the thing that i’ve seen again you know i i do this full time
54:28
and i’ve done this full time for two for for a few years now and so i get on the phone with
54:33
parents and what what happens is this is changing as genetic testing is happening earlier for id
54:40
but the average course is seizures lead to genetic diagnosis lead to neurology lead to anti-epileptic
54:47
drugs and then the seizures are under control and then the parent starts dealing with the sleep
54:54
and the behaviors and they come to me and and i’m like
54:59
well what meds are you on and they rattle off all the usual suspects all the aed’s and i’m like anything for anxiety anything for impulse control
55:08
and they’re like no no one’s ever talked to me about that and i think you did mention anxiety
55:15
what what what we what we’ve when you get past the aed conversation the next two conversations i have
55:23
are first ask your doctor to think about like does your child feel anxious do you think there’s
55:29
anxiety right i mean one of our one of the smartest parents in our group who’s a you know got a got an adult child and has a phd herself and i we were talking it’s a whole
55:39
other conversation which i should i said what is kindness first in gabby and she said kindness is consistency because anything else messes with their world and creates anxiety and so while
55:50
i’m not all parents are terrified about what’s happening to our children’s livers and we’re not i’m not necessarily pro-medication i have seen in my own son anti-anxiety and anti-impulsivity drugs
56:03
make his days easier to get through so i’m i’m curious so question for you there is how
56:09
do you feel about that statement slash where where do you how do you think about sequencing
56:14
discussing or recommending those meds in the in the context of aeds because i always i feel like aed’s always happen first and that’s probably appropriate yeah i have
56:24
a second point but i’ll let you answer that one yeah yeah so i think uh i think
56:29
i agree with your statements that you’ve made i think it can be extremely helpful um to address
56:37
impulsivity anxiety and that that’s how i i approach it i think i have a lot of
56:42
discussion with the parent um about what we think is the driver of the behavior is it just purely
56:50
an attention impulsivity like it happens child can’t even inhibit like
56:55
or is it rooted more and no there’s clearly things that make him or her anxious and then we see it
57:01
because that would affect like the choice um as to whether you kind of go more anti-anxiety
57:07
route or you go more anti-impulsivity adhd meds type of route um i think
57:14
i think it is challenging when you’re already on anti-epileptics more so just from the standpoint of like you just have to look out for interactions and things like that but there are plenty that can
57:24
be used hand in hand and that we often do use hand in hand if i’ve ever if i’m ever unsure i’ll just
57:29
consult with the neurology colleague about you know what they think is the true risk and the tough part is sometimes there are risks but in reality you know like what what are those risks
57:39
what are the risk benefits for this child and the degree and severity of this behavior and you know um so sometimes it is kind of a peer-to-peer conversation um but i don’t know if that answers
57:49
your question but i think you have to figure out like what’s the root what do we think is the root and then just try something and like i said before one thing at a time and don’t be too timid i mean
57:59
if it’s okay go up you know see maybe that child’s metabolism is higher or whatever the case may be
58:04
which gets us to pharmacogenomics which i won’t ask you about but it’s my new favorite topic um cool i think we should do them on all singaporeans because i think i think i
58:13
think what’s risky is an untreated singapian who’s who’s impulsive and anxious yeah yeah in
58:18
society i think it’s terrifying um but so the last question and then i’ll and then i’ll open it up
58:24
actually two more points i always have two more points the one thing you didn’t mention that is the next thing i always ask parents is gi
58:34
and i’ll just i’ll just flag it for you for the next singapian when parents are losing their mind and they’re like drugs behavior house torn down child eloped whatever i’m always like when is
58:45
the last time they pooped and they’re like why are you talking to me about poop and and i’m like well
58:51
when our kids get backed up seizures and behaviors skyrocket and i’ve seen this like again and again
58:57
and again and again and again and i think it’s something that people just we don’t folk we don’t
59:02
folk we people don’t intuitively index on when was the last time my kid pooped when everything else is going wrong yeah but then again i don’t have the hard data on this yet but i’m sure so we’re
59:13
going to get some soon you know the whole the trifecta including jimenez gomez jimenez gomez dalman and moshiri are these three doctors working on gi issues for singapore in florida right now
59:25
and i’m sure they’re gonna show this some way um when our kids get backed up things go fall apart
59:32
and i’m wondering if that’s if if it’s how what triggers you to refer to gi or to think about that
59:40
yeah no i and maybe i should have like made it more of a i think i was rushing towards the end to
59:45
make sure i finished but in the last slide about quick my my first quick tip go to’s for behaviors communication and then in the other category is is pain and i i i as a clinician place you know
59:55
dental constipation i place a lot of those medical reasons under that but i’m glad you brought it up because i think it’s i think constipation is by far if i’m thinking anything medical is by far
1:00:06
the first thing i think about the first thing i ask about um and i agree a lot of times i’ll just
1:00:13
i think sometimes even kids even if they are stooling every day you know pooping every day
1:00:18
whatever term you want to use it still might not be that they’re cleaned out i mean there’s a lot
1:00:23
that could be in there and they’re still pooping every day so i talk to parents a lot about that um
1:00:29
that maybe is worth just a trial of a weekend clean out and we’ll do you know you know hit
1:00:34
it hard with a couple of medications for a few days when you know you’re going to be at home and just see if that helps it’s not going to harm to try to clean it all out you might have a few
1:00:43
miserable days of diarrhea but then um but then you might see a great improvement after that so um
1:00:50
just have to make sure your kid stays hydrated but again um there are there are ways that we can i i agree with you i think that’s a common one that does get overlooked because there’s so much else
1:01:00
going on um but it’s something easily potentially treatable
1:01:06
yeah there’s a lot there’s a lot there yeah there um interesting okay so now i’m i’m gonna
1:01:13
let i’m gonna turn to these questions that are popped up in the chat lauren is doing god’s work translating them for their because people are replying to facebook so question about research
1:01:23
related to environment general education versus special education specifically in the three to six range and then the next one is also from him kevin with regard to exposure from peers
1:01:33
yeah i think i understand yeah i think i understand the question so should we be doing general education and getting exposure to peers are we missing out on that by doing special
1:01:41
education specifically in that three to six age range um that’s a per that’s a great question i think part of it is okay if they’re three to six um in their chronological age so that’s how
1:01:51
old they are you know getting a sense from your developmental pediatrician your school team like where are they kind of cognitively are they more one-to-two are they still working on some core
1:02:00
skills and because i think special education is best for when you really need that one-to-one practice building some core skills um because what you don’t want i think what what lets me know that
1:02:11
a child is ready for general education or at least a little bit of integration into general education is can they communicate in some fashion doesn’t have to be with words but can they communicate
1:02:20
to you to let you know what they need um and um can they uh in the can they
1:02:27
navigate their environment and not um not completely disrupt the classroom environment
1:02:33
because they do have to factor that in as an educator like i mean sometimes that they can they just might need a one-to-one and so that’s what we’re advocating for right so this child is
1:02:42
needs some exposure to same age peers needs a little extra support in that environment can we get a one-to-one for this many hours and you know start a little bit at a time um because
1:02:52
i think like you’re like i think to kevin’s point both settings are valuable for different reasons
1:03:04
yeah i feel your pain on that one kevin and then dr harris what type of specialist if if any would you recommend our kids see for the varying for this disorder syndrome with varying diagnoses
1:03:15
oh for like the bearing development um yeah and i think i think maybe asking who should they see because of all of the variability around
1:03:23
developmental diagnosis maybe because i’m within gap one i mean certainly i would recommend a neural a neurologist um and or genetic geneticist sometimes that’s the same person depending on
1:03:33
where you are we have some neurogeneticists around here um and then i think for the developmental
1:03:38
side um if you have access to a developmental pediatrician like myself that’s what would be called a ddp a developmental pediatrician that’s ideal a neurodevelopmental pediatrician but that’s
1:03:48
i mean those are also very hard to come by in some states there’s one for the whole state so you can
1:03:56
in terms of like the day-to-day you know helping your child uh therapeutically and educationally schools and private therapists can do an excellent job of really giving you a good
1:04:06
assessment of where the child is and what to do next um but in terms of like making the diagnoses
1:04:12
that’s that’s difficult psychologists in the community can make diagnoses of autism
1:04:18
um and intellectual disabilities so if it’s something kind of like you need it you need to have that written down somewhere for your child you can go to a psychologist
1:04:28
in the community which might be a little bit easier to find than a developmental pediatrician
1:04:34
but if it’s private infinitely more expensive and then varena asks an interesting question brenda and i always find interesting topics for conversations brennan leads i should mention
1:04:44
that the the entire german community oh cool how do i see if it’s anxiety or frustration
1:04:51
yep um but i mean that’s really hard and that’s why i think in my slide i said sometimes it feels
1:04:57
like trial and error and that’s not i mean sometimes at some point you just have to try something um i think i think about anxiety when it’s there is an environment a change
1:05:09
something that you you know when my child sees this thing or gets in this environment they
1:05:15
lose it you know they just can’t hold it together behaviorally um to me that suggests that something
1:05:20
is anxiety provoking about that thing that environment um frustration and like distinguishing
1:05:28
that from frustration so frustration can occur for many reasons i think if you know that my
1:05:35
child doesn’t like doing this and so that that’s when this behavior occurs that i would see is more
1:05:40
frustration like i don’t want to be doing this i want to get out of it not i’m fearful um another
1:05:47
you know if you’ve given your child every option to communicate so if you feel like there’s a behavior you’ve given them choices you’ve you know tried to meet see if there’s a need that needs
1:05:56
to be met or um making sure you’ve eliminated the community like that you’ve tried the communication
1:06:03
side because that could be another thing that’s just frustration as opposed to true anxiety i don’t know i mean this is where you guys too are the experts i don’t know mike if you’ve had any
1:06:15
you have thoughts around that i have thoughts about everything i i wish i could think less um
1:06:22
thanks i think it says that i think our kids are incredibly anxious i think i think our kids are having more seizures than we can see i think they’re having more sensory issues than we
1:06:29
realize i think that i think the open field of life is very stressful for them and i have um
1:06:39
i i am not an advocate of pouring endless amounts of drugs in our kids throats i think we have
1:06:46
some some of our older kids especially you find them on lists of meds that have just accumulated
1:06:51
over time and unfortunately no doctor why yeah no doctor has said wait what’s going on here
1:06:56
yeah so that’s something i i that i stress out about about my own my own child but i i i do
1:07:02
encourage families to ask about how about an ssri you know like let’s just try it let’s see and i
1:07:09
and anecdotally i’ve seen good results yeah i think to your point that’s huge too as a
1:07:14
community as a foundation gathering that anecdotal data right i mean you you are the ones seeing and
1:07:23
experiencing what’s been helpful um and i think that’s something that as a clinician
1:07:29
i would find very useful um and it would it would make me help help me not to feel like it’s as much
1:07:35
trial and error if i’m like okay this percentage like this population of st gap one families have told me that this has been helpful and i do it a lot you know anecdotally sometimes we’re
1:07:45
thinking about adhd and if a parent is like oh i have adhd and i took this medication and it was
1:07:51
like changed my life in a positive way then i’m gonna use that one for their child because it’s i mean it’s it’s the same family member so there are there is information that we can gather
1:08:01
um anecdotally that that can be really helpful when we’re making these decisions where it’s a
1:08:06
little bit of trial and error and that’s where the pharmacogenomics thing comes in right like
1:08:12
you know i i can’t wait for insurance to start covering that because i really think especially when i study and talk to the the older kids like the my kids i mean the 20s the 40s
1:08:22
karen is 66 and i thought when i look at the meds some of these adult patients are on it’s a lot of
1:08:28
um psychiatric support yeah yeah cool um other questions from the greater audience
1:08:36
there was something in the chat on the the the one that i can see the zoom chat um do you see a lot of paradoxical reactions to medications in patients with sin gap um it must
1:08:46
have been just to you i don’t see that one yeah oh no no it’s on that yeah um so again this is where
1:08:51
i’d love to hear from you i i because i don’t know that my base is enough to make any generalizations
1:08:57
of the patients that i’ve seen directly i find that many children with if it’s any kind of
1:09:05
given genetic diagnosis or neuro um developmental diagnosis i feel like it’s i never can guess how
1:09:13
they’re going to respond i think it’s always a possibility and it’s a little bit more likely in in the populations that i see that it’s gonna do the opposite i don’t know what have you guys seen
1:09:25
so i’ve we have seen paradoxical we have seen some crazy stuff we’ve seen some um on the aed
1:09:31
side i’ve seen paradox goals to kephra and anfi that were notable and then um
1:09:38
i’m not a doctor i’m not making medical advice i’m sharing anecdotes on the impulsivity side
1:09:45
some people have had great luck with want facing er
1:09:51
and there have and that is a constant topic of discussion and there has been a couple of
1:09:59
paradoxical responses to that for that yeah those are common the alpha agonist lumpus and quantity
1:10:04
and those are common ones that typically do fine but then some children it’s just the opposite you
1:10:10
know we’re trying to help with sleep and behavior and then it does the opposite um yeah it’s un it’s
1:10:15
hard it’s unusual but it’s weird and and and the thing the other thing about our kids is they just seem to be so sensitive to meds like a smallest change is just yep yep and i think that’s another
1:10:26
good thing to take away is like your physician you want that’s another one of my policies i’m sure
1:10:31
i think it’s hard because we want to do something we want to help but we want to fix it fast but uh i always like one change at a time and like inching i’ll be like inching up um because of
1:10:41
that because i think it’s just like you would think that this tiny dose isn’t going to you know
1:10:47
make that big of a difference but it might for some children well the citizen data i will say
1:10:54
is available to any researcher or clinician so if you ever wanted it you could get um
1:10:59
standardized normalized data on 100 and i think the next data release will be in about a week and it’ll be 150 patients there including their full med history yeah so you can just make a
1:11:10
table work and show you pretty cool stuff i think part of it too is just like education
1:11:15
i mean i’m even thinking about as a developmental behavioral pediatrician like how do we disseminate
1:11:21
things quickly i think you know going back to like the genetic testing piece and like
1:11:26
you know like i i yeah people have found out a lot of good information and we’re just not disseminating it fast enough um because that’s like you think that’s news to me i need to go
1:11:35
look at that so here’s a real here’s a question i mean a lot of my questions i have an agenda as you can tell but like this one is a sincere question to you parents come to me and they
1:11:44
tell me something cool that happened and i was like oh my god that’s so fascinating
1:11:50
well how do i what again like what’s the magic words i or the parent needs to use back to
1:11:56
the clinician to get them to write up a case report because there’s some really interesting things that i think are either sentinel for our community like i’ve heard this story five times
1:12:05
and i wish to god it was in the literature or so weird i want people to know about it
1:12:10
how do we encourage overworked over-scheduled tired but very capable clinicians like yourself
1:12:18
to write a short case report and get it into the literature ask them if they have a med student
1:12:27
and then what’s the appropriate stipend we can offer that med student like i’m willing to pay for this stuff i really we really need this in these stories to be told
1:12:36
yeah no i i completely agree with you i think um i mean in full disclosure i think
1:12:44
my brother has autism and i think some of the most fascinating things i learned about autism are through my brother and so it’s like i yeah i hear you like there’s just something there where
1:12:53
a part of me is like man if i had all the dollars and time in the world i would like research this thing that he’s telling me you know and figure out how to research that but um
1:13:03
in in seriousness i think i think you’re right what the issues are time time and overworked
1:13:10
and um if you can find a way to alleviate that and then you know it maybe maybe we can talk offline
1:13:21
about a stipend no i’m not i’m not sure i’d have to think about that but i i do agree with you like don’t give up on it because i think that is how we’re gonna have to get the information out there
1:13:31
is through writing up the things that we learn from from families um
1:13:38
oh sorry i don’t want to forget tim also asked a question about the cost difference between the cma and a whole egg zone it’s much closer now than it used to be but
1:13:48
yeah but do you actually know that i don’t know the numbers off the top of my head i mean cmas are dirt cheap i think insurance gets away with like we’re talking about digits right
1:14:00
CMA is three digits uh an exome our genome is down to low four digits whereas it used to be five
1:14:07
yeah yeah good summary but privately tim i mean private pay you can get these for not much and
1:14:14
like i just said like through our partnership with ambit which i haven’t even announced yet like things are happening so fast they can’t even answer but um through our partnership with ambit
1:14:22
through behind the seizure if you if someone needs testing we can get them tested right um we really need to we really need to find more patients because they’re out there
1:14:35
yeah cool oh i want one point of order as you keep doing this great presentation dr harris
1:14:42
you mentioned the syngap1 foundation i’ve heard of them but they’re not us we’re the syngap research
1:14:49
fund um i think colloquially we’ve been referred to as a syngap foundation and it’s odd that
1:14:55
the other group changed their name i don’t know somebody said that they’re trying to impersonate us i don’t think that’s really happening but if you could just add the syngap research fund
1:15:05
certainly that i agree with you i thought i was talking about the same thing which is embarrassing for me but no it shouldn’t be embarrassing i think it’s intentionally confusing and very
1:15:14
and it’s anyway you don’t have time for these details but if you could add singapore’s yeah of course of course and then send you guys the um the slides yeah it’s all good we’ll talk to
1:15:25
the presentation please do i can even send you a clip of myself saying syngap research fund
1:15:32
no it’s all right we got it olga dr harris thank you so much that was wonderful and we’ll get you
1:15:39
the information on um cook’s children’s for the end of june yeah perfect wonderful for me
1:15:45
i learned from you guys so yeah that’s that’ll be great andrade and perry are good and the
1:15:51
and the dravet meeting if you weren’t planning on going there’s going to be a lot of heavy hitters there too which would be some great clinicians yeah and then uh thank you tim and then next week
1:16:04
we have what’s what’s next week’s webinar olga they’re coming fast and furious uh dr Rumbaugh
1:16:10
dr rumba on splice forms yes which will get to what we talked about at the top about the three prime and the five prime and then the week after that is some something else right um
1:16:19
it’s the probably genetic testing finding more patients yeah awesome all right thanks i have
1:16:26
one quick question before we go that might help dr harris and help me understand too
1:16:33
she’s talking about fragile x testing etc syngap is only coming up through the epilepsy panel
1:16:39
or i mean do we have a specific test that if dr harris suspected she saw a sydney gaping patient
1:16:46
she said okay can we send them directly for that test or do that it has to be the whole exome or
1:16:52
dr harris you want to take that first you want me to uh you can weigh in um because i like i
1:16:58
said because i’m not getting the chance to send a lot of these myself i’m having to refer out to genetics i would think you could do sequencing specific to the gene um like that you can and some
1:17:08
others but i don’t know if y’all are i don’t know if you can do it so so we have so the answer to
1:17:13
that here’s my answer and i welcome correction for dr harris the CMA is like a 30,000 foot picture of
1:17:19
the chromosome and if a chromosome is misformed like you would see in fragile x you get that but it doesn’t zoom in on the genes right which is why it’s so antiquated and cheap and relatively
1:17:30
useless but the so the question is is ogre one of decisions right how do we catch a mutation
1:17:37
in syngap one and that’s why people prefer exome and genome is because exome and genome look at the whole exome slash genome and say okay where are their variants and what do they mean and if
1:17:46
they have a clinical indication of id or epilepsy whatever they will zero in on neurological genes but because it’s cheaper and this is this is this is rapidly becoming not true as the cost of exome
1:17:57
crashes to tim’s question you’re seeing these panels go away but they’re still cheaper they’re
1:18:02
still easier to get through insurance so people still do them so we are on an epilepsy panel because of peter from our boards advocacy we are now on cp panels we are on id panels so if you’re
1:18:13
on an id panel an autism panel a cp panel what am i missing guys there’s probably one other we
1:18:20
we have we have talked to gene dx in vitae ambry variantex and others to make sure we are in as
1:18:26
many panels as possible so that we can catch and it’s just and that’s just a decision right there’s 400 panels on the invite epilepsy panel 400 genes on the nvt epilepsy panel we’re one of them
1:18:37
and so when i talk to other rare groups and they say how do we get on these panels it’s this old school you call the company and be like put me on the panel
1:18:48
yeah i think i definitely i think that’s a good explanation the CMA i see it is like you’re
1:18:53
looking for big copy number variants so it’s a big chunk deleted or is a big chunk duplicated
1:19:00
yeah and so if if the big chunk that was deleted contains the same gap gene maybe you could like
1:19:06
make some differences but yes yeah exactly and then fragile x is like completely separate
1:19:12
because even a CMA will miss fragile x that one you’re looking right because it’s a repeat sequence a triplet repeat so for that one you’re like okay i’m looking at that exact gene to see
1:19:22
yeah and then it looks like there was a comment to in the chat that sanger sequencing that’s what i was trying to think of you can’t yeah that’s what i was going to bring up yeah you can sequence the
1:19:30
specific gene um oh but interesting so there have been families who’ve done that though and it still came back normal and then later the exome caught it so it sounds like egg zone maybe
1:19:40
it’s the and i think verena’s other question is super interesting the point
1:19:45
verona is so smart she’s talking about you know also angelman and rhett panel because
1:19:52
we did all of that for yeah took us five years and i would i wouldn’t i wouldn’t encourage someone to go look at syngap just because you know a syngapian and an Angelman
1:20:03
and an STXBP1 and whatever in the early years they they all feel pretty similar frankly and it only after a couple years that they um that’s actually that’s a great point a lot of overlap
1:20:15
developmentally like speaking just from my area of experience with angel men and and like kind of
1:20:20
the degree of the delay and how it presents yeah it’s interesting the thing about the angels though
1:20:26
is our kid our kids start as angels and then they visit the dark side until they’re about 20. yeah
1:20:34
and it’s true in a schizophrenic matter like six days you know 20 hours a day my son’s awesome
1:20:42
and then yeah and then you know aggression and behavior are real issues that’s why i look like this
1:20:50
thanks very much i’m going to check that out make sure yeah me too yeah huh okay well thank you dr harris i’m we’re grateful that you see our patients
1:21:01
and we’re excited that you’re fresh out of fellowship and you’re so young and smart because
1:21:07
we need all the syngap experts we can get in this country because there’s i see patients get diagnosed every week yeah and you know they’re coming
1:21:14
yeah no it’s it’s fascinating to me i like i said my area of research is autism broadly i think the
1:21:20
quote idiopathic autism is fascinating because we’re gonna find you know what that is but
1:21:25
there’s other forms i do a lot i do Angelman clinic here i do fragile x clinic and i do mech p2 duplication and ret syndrome clinic because of that reason i’m like they all have their own form
1:21:35
of autism it’s part of their genetic diagnosis right and so yeah we need to anyway back to their
1:21:40
original topic of like the same type of services would be helpful um and so funny story and just
1:21:47
put it out there that you know this is syngap1 autism this is idiopathic autism it’s all you know
1:21:54
i can’t wait to read your paper you should really get a citizen hopefully the way things move you know it might be the years down the road but thank you guys so much for teaching me
1:22:02
as well i i’ll just i’ll just funny story like there’s a drug company working on rett and syngap1
1:22:09
and we they had us present at an all staff and so the re the rep people have been around forever right they have way more money than we do very professional they have a beautiful presentation
1:22:18
and marta who’s on a doctor on our board um presented our slides which were my slides which
1:22:24
weren’t as pretty as the red slides but she did an amazing job presenting them and then i got this question from someone in the audience about like why is this and i was like guys rett syndrome was
1:22:35
first diagnosed by dr rett in 1960 something right you’ve had decades to diagnose patients and then
1:22:41
only in what the 90s did we find mechp2 and say ah medp2 causes red you have to understand syngap1
1:22:49
the gene was identified in 1989 the first patient in 2009 i had those numbers wrong round numbers
1:22:55
1990 but 2009 first patient right we’ve only been diagnosing patients for 13 years the only way you
1:23:01
get this glorious diagnosis is if somebody gets through insurance and gets a diagnosis on the
1:23:07
gene yeah so it’s talking like yes rett syngap they roll off the tongue together these days
1:23:13
but historically they’ve had so much longer to educate people see hand flapping they think rett
1:23:19
and they they diagnose but syngap they’re like well what am i doing it’s a totally different sort of way in and a disease strictly defined by a genetic variation it’s just the system is
1:23:32
still getting its head wrapped around it you know yeah it’s a good way to put it still getting its head wrapped around it but but people like you will help them do it faster so we’re grateful
1:23:42
so i’ll work on the dvp side of things the developmental peds side to get it out there please do i think you guys are essential yeah all right thanks guys bye everyone