An NFXF Webinar with Dr. Walter Kaufmann

Autism spectrum disorder and Fragile X syndrome are often linked. In fact, numerous small and parent-reported studies have shown that a considerable percentage of individuals with FXS also carry a diagnosis of autism. But many questions remain unanswered.

The first large-scale study looking at autism in FXS was conducted using FORWARD data (a project coordinated by the National Fragile X Foundation). With this new data, we discovered a higher percentage of autism in the FXS population than previously reported. Findings also showed greater behavioral impairments, and greater disparities between expected and observed behavioral treatment use, for those with FXS plus autism than those with FXS alone.

Dr. Walter Kaufmann, the principal investigator for the study, discusses this topic and answers questions in this NFXF webinar, “Autism Spectrum Disorder and Fragile X Syndrome, Co-Occurring Conditions and Current Treatment.”

You can view the webinar below or on our NFXF Fire TV app. For more information, also see Fragile X & Autism, and from our treatment guidelines (i.e., consensus documents), see Autism Spectrum Disorder in Fragile X Syndrome.

Autism Spectrum Disorder and Fragile X Syndrome, Co-Occurring Conditions and Current Treatment

Walter Kaufman, MD
, Director, Center for Translational Research, Greenwood Genetics Center, South Carolina

Jayne Dixon Weber
, Director, Education and Support Services, National Fragile X Foundation

Full (Unofficial) Webinar Transcript

Jayne Dixon Weber: Good afternoon everyone, I would like to welcome you to today’s webinar, “Autism Spectrum Disorder and Fragile X syndrome, Co-Occurring Conditions and Current Treatment” by Dr. Walter Kaufmann. I’m Jayne Dixon Weber, the director of education and support services here at the National Fragile X Foundation.

Today we have Dr. Walter Kaufman. He is a clinician and a researcher with a focus on developing treatments for genetic disorders associated with intellectual disability and autism. He’s the director of the Center for Translational Research at the Greenwood Genetics Center in South Carolina. Before arriving there, Dr. Kaufmann was a professor of neurology at Harvard Medical School. His research uses a multidisciplinary approach to understand the basis of cognitive and behavioral problems in children with genetic disorders associated with intellectual disability and autism spectrum disorder. He’s one of the leaders in the study of autism and Fragile X syndrome. He’s a member of the Fragile X Clinical and Research Consortium and has published more than 200 journal articles. He’s also served on several editorial boards as a reviewer for over 90 scientific journals. Welcome Dr. Kaufmann, it’s a pleasure to have you with us this afternoon.

Dr. Kaufmann: Hello everyone, thanks Jayne for the kind introduction. This is my first webinar, and I’m very excited to be here to talk about this important topic. The focus is a publication that came out in June 2017 in the journal Pediatrics, and I want to emphasize that this publication was possible thanks to the participation of many of you in a project called FORWARD, which is funded by the Centers for Disease Control and Prevention and administered by the National Fragile X Foundation. This is a very important project, taking advantage of families attending clinics, which are part of our [Fragile X Clinical and Research ] Consortium.

We call data, and we try to understand the most important issues that affect individuals with Fragile X. Initially it was about children, but we’re expanding this project to include adults with Fragile X. And certainly autism, the diagnosis of autism, or the new terminology, autism spectrum disorder, is a common one in Fragile X.

Here you can see that there are different metrics, different ways to measure the relationship between Fragile X and autism.

Number one, Fragile X syndrome is the leading genetic cause of autism. Depending on the study, anywhere between 2% and 6% of children with autism are diagnosed with Fragile X.

On the other hand, if you look at it from the Fragile X perspective, about 40% of individuals with Fragile X are diagnosed without autism spectrum disorder in our clinics. That proportion is targeted in males and females. There is a probable higher rate in males with Fragile X being diagnosed without the autism spectrum disorder.

Now the central issue about doing this study was to answer the question, “What happens when a child with Fragile X is diagnosed with autism? What difference does it make?” So, we focused on identifying the different neurological problems that were affecting those who got the diagnosis of autism. From this study, we learned that there is also an age dependence.

In children, those who are ages 3 to 11, there is a higher proportion of a variety of problems. Those are mainly hyperactivity and ADHD-type symptoms. However, anxiety is now more common in those who got the diagnosis of autism. While on the other hand, the problem is more prevalent in those who are older than those who are in the teenage years. So, you know there are higher proportions of individuals who have neurologic and behavior problems and they tend to be more severe in adults with autism, but there is an age dependence.

We also see that seizures are more common at any of these two ages, children between the ages of 3 and 11 and teenagers between the ages of 12 and 21. Those who received a diagnosis of autism had a higher frequency of seizures. In terms of sleep, the difference is much more obvious only in those who are older, in the teenagers. It doesn’t mean their sleep problems are not present in those without a diagnosis. They’re actually common, but they are more common in adolescence, in the teenage years with Fragile X and autism.

The behavioral problems that affect individuals with Fragile X are diverse. So, we examine each one of them. But only a few were more clearly common in those diagnosed with autism. In the case of children, disruptive and aggressive behavior is more common in those who got the diagnosis as well as ADHD symptoms and hyperarousal. As you know, hyperarousal is an excessive response to sensory stimulation. It’s typically auditory but not only auditory; it could be other sensory modalities. Other behavioral problems were now more common in those with Fragile X.

When you look at the teenage years, one other thing that this study showed is anxiety is more prevalent in those who got the diagnosis of autism. And that is maybe a little bit surprising because we also see anxiety in children. In any case, anxiety is a very important problem, particularly social anxiety because it is a very distinctive feature of Fragile X.

A particularly challenging time period in everyone’s life is social interaction. Social life really is a major part of adolescence, so that is probably one of the reasons why it’s more prevalent at this age. In addition to looking at neurological capacities the children have, we also look at the use of medications and we found what we expected. Aggressive behavior is more common in those with the label of autism. There is a type of medication that is used for this common behavior in autism. We’re talking about a medication we call atypical neuroleptics. Some of them you know by their brand name like Abilify and Risperdal, those are medications that are typically used for these behaviors. So that wasn’t a big surprise, it’s confirmation that some of the behavioral problems are more common in those who have a diagnosis of autism.

Now, in addition to that we look at what type of non-pharmacological treatments—meaning no drug treatments—are those children with autism receiving. We look at everything that is under the therapy and service label. What we found is that in general terms the children with the diagnosis of autism tend to use or receive more services. That’s very clear for services across the board for those in preschool. But by the time the children are in a school from K-12, which is 5 years and older, actually we were a little surprised that while many services are more prevalent and more frequent in those with a diagnosis of autism, some services that you expect to see in children who were diagnosed with autism were not more prevalent and more frequent. And we’re talking about services that have to do with autism like social skills, applied behavioral analysis—what we call ABA. And we were surprised about that … and we try to understand these and to compare [them] with what happened in the population with autism. And that’s what this slide is showing [above]. For instance, ABA, which is a type of behavioral therapy, is widely used in the adolescent field. Children who are in the pre-K age segment, those who have the diagnosis of autism, 26% of them are receiving those services. But those who are older, who are in the K-12 in the school period, only 16% are receiving those services. And both numbers are lower than what we see in the general population with autism, which is about 36% percent. So that was a surprising find.

Many of the findings that I presented to you before were not a complete surprise. We have suspected them, but because we were doing the study with a smaller sample—over 100 individuals with Fragile X were being analyzed—it was important that this data be confirmed. But this is completely new, this information about utilization of services. So why do this? Well, because we want to make sure that we understand what it means to have a diagnosis of autism, and what are the problems that children and teenagers with Fragile X can have. So, like I said, some of those that are being reported is for the study. But we are having a larger study called fumitory study. A study that could be more definitive is that we can have information for planning. How is this used? For clinicians who are seeing children with Fragile X, knowing this information is important because we can emphasize the type of problems that they have to pay attention to.

An example is, in children who get the diagnosis of autism at age 3 or 4, we are aware that soon after that they may have aggressive behavior, disruptive behavior. And perhaps a way to deal with the situation is to make sure that the environment of that child is one that makes it less likely that they will display those behaviors.

Our ultimate goal is to have a good quality of life for these children and not necessarily to write more prescriptions. It’s to have management of the environment, to try to create the conditions by which it can be better adapted to his or her own situation. Whether it’s a school, home, or what we call community. Going shopping, going to recreational activities, playground, etc. So, this is helpful for clinicians and it’s also helpful for clinicians and other therapists who are providing services [that] don’t include medication.

To make sure that we give that proper treatment, it’s very concerning that they’re getting more ABA when they are very young. They are not getting that in the same proportion when they are older, when they are … school age. So, this is actually information that we can use when we are interacting with the schools where these children go. In clinics, we already do that, many times we’re involving the IP process. When involved in advising the family, you can fail also in terms of a bigger policy. We may go at the state level—even at the federal government level—to explain the type of services needed with Fragile X, but I think that those who get the diagnosis of autism need more planning at the local level.

It helps with the management of the children and management that could be more preventive. And also, it helps set a bigger picture of the type of things that advocacy groups like the National Fragile X Foundation do. So, because the diagnosis of autism is so important, have we been concerned about how good are we doing?

DSM-5 is the abbreviation of the [Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition] and the most recent one was published in 2015. It’s about four and a half years old and we have been looking at how DSM-5, version number 5, is doing in terms of diagnosing. And what we need to be concerned about is the quality of the diagnosis. Are we doing a good job? We have been concerned that the intellectual and behavioral challenges of our children may lead to a diagnosis that is not accurate—[or] lead to underdiagnosis or overdiagnosis.

For full disclosure, I was a member of the committee that issues this style and … anything inside is a working progress. So, while we can start as a follow-up to this work and the relation with this style, we can begin to look at how we can do the diagnosis. So, as part of our very important project we’re collecting data on a couple of autism-related measures. This one is [a] social communication questionnaire and the social responsiveness skills. The names are not as important as to tell you that they’re measures of behavior and … which way that data can improve the diagnosis.

We can miss some of how these measures[?], which I’m mainly screening but we can use them as supportive measures for diagnosis. We are working on improving that and incorporating them into the practice in clinics. So, this is something that can be applied for [future] clinics and hopefully not only that, but we’re about to publish a paper on the subject. So, the clinicians who are seeing children and teenagers with Fragile X and autism—Fragile X you know who are now part of this—also learn about this and become more attune to the challenge of the diagnosis of autism in this population. That’s all that I wanted to mention today and I’m ready to begin the discussion … about your questions, clarifying what I just said, thank you.

So actually we have our first question and it says, “Dr. Kaufmann, thank you for your presentation. What would you recommend as current diagnostic best practice for ASD in children with Fragile X. Syndrome?”

So … that’s a good question … and we’re still recommending for clinicians to use the DSM-5; but to try to incorporate as much information as possible. To try to be … strict in terms of applying for use … to make sure that a diagnosis is not influenced by their communication skills—[the] level of communication and skills of the child or teenager or even adult—because that is not a factor that should influence the diagnosis. It’s not the level of communication skills but rather the use of the communication skills, [and] how they are used for social interaction and communication.

Another concern that we have, that’s a general concern, is about a variety of genetic disorders that go along with a level of intellectual disability. Specific to adolescence, we think that anxiety could lead to a potential overdiagnosis. So, to make sure that the symptoms are taken into consideration for their diagnoses and not influencing … it being influenced by anxiety, hyperarousal, and some exaggerated response to sensory stimulation could be another factor.

So taking into consideration the type of behavioral problems and the type of cognitive problems that the child or adolescent may have, and now … making sure that we are not the ones influencing the process of that diagnosis. I think that we are not yet ready, but we will be very, very soon, to recommend the use of a modified social communication questionnaire and social responsiveness scale. We are going to publish which items for those scales are important, because the scale was developed for children with autism in general or at risk for autism. And again they could be affected by this problem I just mentioned. So, we have selected through a process of very careful review … items on those scales should be used; we have gone from 39 items in the SEQ to 25. I don’t know exactly the number that we are at for the SOS but … 65 down to 50 something. So there has been a reduction of the items. So we have that we’re working to actually recommend the use of that through our projects community. But also by publishing the data, these recommendations are going to be available to the community.

One of the questions that a parent sent in was they have found out about using a sensory diet or even incorporating sensory aspects throughout the day. They’ve read that it’s been recommended for a lot of people with Fragile X syndrome. Is that true when you have an autism diagnosis too?

As I mentioned, children who have the diagnosis of autism tend to have higher frequency of sensory problems. So, they definitely tend to have more of that. Any intervention that deals with sensory processing is going to help.

In the position of a particular child or teenager—because some of them don’t have the problems of similar severity … but if the sensory issues have been identified and a specific therapy has been implemented as part [of] that, it will seem to make things better. You have to [remember] that the core problems in autism are about social communication interaction plus … what we call restrictive behaviors. Those are the core symptoms. We work very hard to identify treatment for the core symptoms of autism. Unfortunately we don’t have them here. That has been frustrating long past that. Everything that can be done to modify autism behaviors is going to be helping with communication problems. So, in the war with Fragile X and autism … we have sensory problems. The sensory problems diminish in general. Any intervention that is trying to reduce [or] minimize the social communication in time is going to be more effective. And overall, like I mentioned before, what we intend is to improve quality of life. So we hope to make this being very confined. We are going to make use of that in order to be in class, perhaps to go to a shopping mall where there is a lot of social information. I call it the Starbucks effect. I use that word because you enter a Starbucks or one of these coffee shops where people are screaming and they are ordering, [and] there’s so much sensory information that for many in the world without disorder that have sensory is very difficult to manage. We try to modify it some away … we are going to make more [?] that that individual, that child could, you know, be in [some] type of community setting. So definitely, any treatment of [associated] problems—[from] ADHD to aggressive behavior to anxiety and hyperarousal—I want to make a difference in terms of improving the overall quality of life and even … in behavior.

I see, so we’re speaking of anxiety. So what type of strategies do you recommend for addressing anxiety in children with Fragile X and autism?

It is like any treatment, it has to be very much tailored for the child. Some children can respond, particularly older children who have better communication skills. Maybe they will be able to respond to some type of modified cognitive behavioral therapy, which is a treatment that is used in anxiety, others include hear therapy.

Other [types] of behavioral interventions are also effective. Dealing with and anticipating anxiety in a real situation—[say] they are going to go to the doctor—so [it’s about] the preparation for those events, preparation for transitions. So that is likely a strategy that can be used in the general category of behavioral management. All the way from the issue with scheduling to more complex therapies. I cannot give a single recipe for everyone with autism and anxiety because there is so much of a difference.

Now medications may be there also and certainly we tend to use medications that are used in our general population for anxiety and those tend to be what we call SSRIs. And actually, we know some that seem to be more effective with Fragile X and I will use those. Also, even some of the medications that are used for treating aggressive behavior seem to also help with anxiety. The commercial name is Abilify and seems to be more effective than Risperdal for dealing with anxiety, at the same time dealing with aggressive disruptive behavior. So there are a number of strategies that can be applied … to do as much as we can without medication but the medication won’t necessarily reduce it. Having said all that, of course right now we’re happy about all the options we have and the reason why we keep trying to look for medication that’s more effective specifically for Fragile X is that we can go to the root of the problem.

I know that there are some strategies online, for example, addressing anxiety … so, what I’m hearing is that if you have a child who also has a diagnosis of autism, it isn’t very important to really figure out those strategies and what worked for your child because of the impact that autism can have on Fragile X syndrome.

That’s correct. I mean I think that everything that we can use to minimize problems for these children is critical. Because that will make them more engaged … in the type of therapy that we’re trying to use for the core problem—I mentioned that we will be in the study published in June—we were surprised about seeing that children who got the diagnosis of autism are not using or not receiving social skills and therapy in greater proportions. But in order to take advantage of that social skills therapies or any other type of other problem, we need to try to minimize all the other problems that they have, so we are more proactive about treating anxiety, treating hyperarousal like I mentioned before. It’s all very customized because, as you can see, the range … a child with Fragile X syndrome can have is numerous. But they [are] not necessarily all in the same individual so it had to be really focused on … the problems of this child or adolescent.

I’m going to switch gears just a tiny bit. In your experience, when do children with Fragile X typically get diagnosed with autism? Is there an age when the autism symptoms begin to display in children with Fragile X syndrome?

I don’t think that we have that data, and I don’t want to give my impression only because … it would start like the one we publish in June, we were trying to go beyond a small series.

One thing that is true is that some children are diagnosed with autism before they are diagnosed with Fragile X. The average age of diagnosis of Fragile X continues to be about three and a half. So, some children are diagnosed with autism before that, so that’s a group in which the diagnosis of autism is before the diagnosis of Fragile X. So, Fragile X, I would say that if they go to a place in which there is a lot of experience with Fragile X and the other [related] mental disorders, they get the diagnosis relatively shortly after that.

I know for the most part it couldn’t be true that within age four or five, in general, the diagnosis of autism is much more obvious. We want to make that much earlier. And remember, we want the diagnosis but we want the correct diagnosis. We don’t want anyone with Fragile X to get the diagnosis of autism because that happened [back] when … people were not familiar. So, we want to make the right diagnosis and that’s the, you know, the picture as we move [forward] with [an] improved diagnosis approach.

We’re going to look into these issues, this is an excellent question, and we’ll show you how much we can get from this looking forward, and we look and look at every issue out [of] this publication that I present, they have led to other studies and going to lead to more follow-ups, to try to get deeper and deeper into the issues that affect the individual with Fragile X.

Here’s a question from Walter, he says, “My child does not technically have autism though he has many similar traits, but in order to receive certain benefits through the school system, it’s like a switch gets flipped on when you have an ASD diagnosis. I’m torn over the ethics of pushing for an autism diagnosis when I can get more services and so it’s kind of … what’s the sentiment in the medical community to go ahead and label my child with autism just to get more services?”

This is a very important question and this dilemma is not only [a] dilemma for parents, but also for clinicians, because we want the best for our patients, and where we struggle about providing the diagnosis—that we may think that it is not accurate but is the only chance to, to get services … and I think it reflects the problem with the system and is a very, very important problem in the United States, but it’s not only restricted to the United States. I was, earlier this year, in Sweden, and I was discussing with my colleagues in Sweden the situation about the diagnosis of autism in general. Not only in Fragile X, but in the world [of those] with [an] intellectual disability, it’s the same situation, even though that’s a different health care system. I think we have to find some way to provide what a patient needs without being so strictly attached to labels—and this is coming from someone who wrote the label—so, I don’t think that … we shouldn’t lose perspective that the most important thing is what [are your] particular … needs, and whether all the symptoms are there, to get a particular label or not, it is … it’s important for the big picture—organizational services and other things that we need—but if someone has social communication problems but … the second component [of] the diagnosis of autism is not there, we should provide the treatment for the social communication problems and not be so focused or fixated on the diagnosis—there is a problem, there is an impairment, we need a solution, and the question has a lot to do with policy and with the organizational services. I’m going to tell you the truth, we clinicians sometimes give the diagnosis of autism because we’re so worried that our patients are not going to get the services, but we know that by doing that we modified the statistics, and at the end of the day, whoever needs to plan for services and [has] … incorrect information, it’s not good—so we have to have different approaches to this with a concern that we have about the diagnosis of autism in Fragile X and other genetic disorders.

We’re beginning to think about getting other diagnoses that are such that point out … to the real problem of the child, and we need to be proactive about saying if a child gets the social communication disorder, yes, it doesn’t sound like autism but that child needs the same services. Some work with autism in that area, and social communication area—this is something that keeps me awake at night and we need to do something about it. I do this type of a study, like the one that we published recently, and the second one about the diagnosis of autism I just mentioned at the end. This time I’m going to provide data so we can go to the appropriate levels, whether it’s legislature or other levels, to get a different approach to providing services.

Well, you know, Walter, thank you for sharing that because I know that that’s … really tricky and so you know, I know, families struggle with that. I’ve gotten emails focused on my child really needs ABA, but unless he has a diagnosis of autism my insurance won’t pay for it. [That] kind of thing, it’s a tricky one.

Okay. moving on to the next one: “My child’s anxiety and hyperarousal directly affects his ability to communicate—whether it is Fragile X or his autism—both directly affect his ability to communicate. I don’t understand how that would not increase communication problems in the DSM-5.” I think that is what she is asking.

I really don’t understand the question. I mean, certainly anxiety and hyperarousal are common, you don’t have to have the diagnosis of Fragile X, autism, or have both of them. All that we’re saying in this study is that the frequency—and probably also severity—is greater if you have the diagnosis of autism, and you can have Fragile X without ASD, and have anxiety, hyperarousal, and in both cases, they are going to improve impaired communication. I don’t understand what is this relationship called communication and with the SM, so I cannot answer that.

Let me see if she adds more in just a minute. I’ll keep moving down. Do you think the sensory processing problems are more of a contributing factor to the aggressive and disruptive behaviors in ASD in Fragile X?

Well that’s a good question, and we always try to understand why a child displays aggressive behavior. To be honest, I don’t think that we all will have an answer and we have to try to find the cause, but I think that, also, to be very cautious about over-interpreting situations.

Probably the best way to make sure whether it’s contributing to—let’s say aggressive behavior—is to have long periods of observation and collecting data, that’s what the oral therapies do, they not only let the ABA expert—which is one flavor of behavior therapy—but other forms to collect data. This analysis, that’s what b stands for, [in] applied behavioral analysis, do you look at the behavior of it, if you will, and you try to see what is the trigger. What is causing the behavior, definitely, we know that if you have communication problems you get frustrated and you may display aggressive behavior. Because of that, if you have anxiety, maybe aggressive behavior—of what is labeled aggressive behavior—says scale response because you’re so-so, we’re [?] by the situation … you want to run and in order to run, you push people around.

It could be the sensory issue, or one with that noise, with all that … so many things happen at the same time and one way to, say, is to match when you don’t have the verbal abilities. So the answer is all the problems that [?] the world with Fragile X are common, that I mentioned: anxiety, sensory stimulation, communication. All of them could lead to something, behavior, independent of whether they have autism or not, so a good behavior approach—to disruptive behavior or any other type—[?] is to try to see, what is the cause or what is—if not the cause—sometimes sounds like it’s such a big world, what seems to be, you know, triggering, to see at least facilitating the behavior, and to try to care, to deal with that as a way to decrease aggressive behavior.

Unfortunately all that I have mentioned involves time, involves having behavioral experts and those new heroics are not available everywhere. Good quality behavioral services are not available everywhere, so unfortunately the solution to the problem in the short term may be medication because the problem is so big, that you have to deal with it right away, but is ideally not the long-term solution. The long-term solution is some type of modification, and environment modification of the way that they, in the world, will try and respond to the environment and decrease the chances that aggressive behavior being displayed.

Well I know they can be more challenging when you’ve set up a pattern. When you try to go to change something, it can take a while before, for example, the child understands that, the environment is no longer going to be. You’ve changed the environment so that it’s knowing you’re going to be overstimulating, or as overstimulating as it was before, so it takes a while to unlearn some of those behaviors.

Right, this is an important point because when maladaptive behavior come on, adapting, here in a problem, behaviors are displayed and in some way, reinforced by the environment, it is very difficult to modify them. When I was in Baltimore at the Canadian Institute and I began working on Fragile X in 1995, the inpatient unit had always seen a teenager, typically 18 years, nonverbal. [Note: Unable to format the following for clarity] When you know that, what autism, as out-patients try to do with the—because that was the only way it was no longer possible to do it as an outpatient by the time I left in 2012.[?] There wasn’t always someone with Fragile X to miss, an index that we are doing better, we have been very big [on] human services earlier and that’s one of the functions of this publication, to say: look at this. If this child comes to you—let’s say that a child comes to you with a diagnosis of autism—then an early intervention service, that, even before the Fragile X diagnosis, if that’s the sequence, by the time that comes to your clinic, be aware that this is a very high-risk challenge, to display aggressive behavior. So at the first report from parents, or the school system, or whoever, your therapist tries to take you to do an intervention that prevents the reforms of this behavior, and that can happen as early as four or five. So, yes, they are trying to prevent the escalation, or the problem is very important, and again data—as the one in the paper—you know, reinforces the cause of being proactive.

Thank you. Here’s another one that’s kind of tricky. I think, I mean, it’s more of a comment, but then I have a question that comes out of it. So, ABA therapies focus on compliance now, this is one parent’s comments, ABA therapies focus on compliance and not mental impairment for my son. We tried ABA from three to five years of age and again at seven and a half years of age. His experience was a great increase in his anxiety because of the ABA. The ABA school did understand the Fragile X and anxiety of hyperarousal. We transitioned to a public school, who did better with Fragile X, but they did not understand the autism issues. So then they went on to home-school. Yes, I got my computer jumped around to teach, you know, coping skills, and teach at his level to help him understand. What they found is the different placements did not understand the co-occurring diagnosis, that I do see. How do you adapt the ABA to someone who has Fragile X and autism? Mouse and Tracy did write an article about that, but I mean I’d love to hear what you have to say.

It’s a very important question, if you are using ABA to extinguish some behavior or even, you know, reinforcing, or a skill, and the context in which … is supply, is one that triggers anxiety or hyperarousal. Obviously it is not a good situation so to me, ultimately good ABA is an ABA that doesn’t create new problems. Now this sounds pretty straightforward but for many children is not obvious that a particular approach that could be very structured and therefore anxiety triggering is inappropriate but at some point the therapist had to realize the situation.

I think that if a therapist is applying ABA and doesn’t know how to deal with anxiety, the [?] autistic symptoms, needs to know, to get … to gain additional experience, to take some courses, because it’s not only Fragile X anxiety as a comorbidity, co-occurrence of autism is not only Fragile X, the high evidence is in the general population [?] the link between anxiety and autism, that now both one, doing the particular testing, new treatments in animals, is of autism includ[ing] anxiety as part of them … the … this symptom that they look for in the animal, is the drug decreasing behaviour that are called anxiety in mice as a way to make sure that the [?] eventually, when I go to human trials we … now that can deal with anxiety, also, and [?] is so close that anyone applying an ABA went for the purpose of dealing with our autistic symptoms, or autism-related problems had to, in being cooperative.

Hyperarousal may be a little bit different because while hyperarousal is also present in children with autism who don’t have Fragile X, some of the elements of the hyperarousal you see in Fragile X are very unique. The auditory component we have with children who have tactile issues, the difficult thing [is that they] cannot deal with labels in the clothing, they had to have a sort of loose-fitting clothing, things like those and even visual stimuli can produce an exaggerated response, but the auditory hydrolysis is [a] very unique Fragile X phenomenon. So I think that I understand that could have been a little bit problematic. So, I don’t know if I had answered the question, but I think that in my view, therapies that would deal with an ABA in autism had to be able to deal with anxiety and to largest and with at least a certain level of height … arousal so I don’t fully understand what happened.

I’m with you, I think that that’s probably what does happen, is that the parents—is that some of the ABA do not take.

It doesn’t take into account, it’s not going to be a problem, those providers are going to have children with Fragile X but children with autism or other causes because it’s so common in autism. There is one thing I want to mention that is different in Fragile X, it  is the prominence of the social type of anxiety, all types of anxiety can be present, but the social side is so prominent and that is, it makes almost, like a label of Fragile X. But, again, autism is such a broad and diverse condition that you see many people who have social anxiety also, so I think that whatever was being implemented needs to be revised because it’s not going to only fail for Fragile X, it is going to fail for other causes of autism.

I agree, I agree. For those of you who are still on, so, you can go to our website and, I think it’s called … the article we have is “Adapting ABA for Fragile X,” or something to that effect, and if you can’t find it, shoot me an email.

Couple more questions Walter and then we’ll call it an evening. What about the child that has missed the window of opportunity when they were younger to get that ABA behavior and now that the child is older and it’s so expensive, so, I mean, you know ABA wasn’t around when my son was younger, and I often thought, you know, how would things be different if he had received it, so what can you give to parents whose kids are older now and they’re discovering ABA therapy?

Right, you know we want to be part of the early intervention autism but it is not available. One thing that everyone had to remember, there is never a period in which you cannot do anything, so probably the type of effects that ABA has on a variety of domains, including cognition, are not going to be there because the window, then the elemental window, was missed. However, any type of the hero intervention and an ABA had been become so closely attached to autism I had to tell you ABA was not initially designed for autism. It was designed for former hero problems in, mainly dealing with intellectual disability, but it was seen as a way to modify behavior by having sort of a very scientific and structured approach. Like I said before, by analyzing the situation and trying to put a plan that makes sense to that particular individual, so the hero interventions are never something that we should rule out no matter how [?], in fact, the story that I mentioned about the unit in Baltimore those teenagers, typically in 15, 16 year olds with autism and limited verbal abilities, right to the unit after being on four or five different medications and none of them seemed to be successful in dealing with behavior. In the safe environment, they were taken off all medication. You cannot do that at home, but you can do it in an inpatient unit, it is specialized in these, and we don’t know what is working here. Maybe by the time that you end up with four or five medications you don’t know why the first one won’t prescribe, and they were taken off the medication, and the approach of collecting data, and try to modify behavior began by the time they were discharged. You know, they almost always are going to make issue, but fewer than they came in, so maybe one medication, because the behavioral intervention had made a difference.

I can provide testimony that it is never too late to modify behavior, and while you know some of the gains that could have been achieved early in life may not be possible at 15 or 16 by modifying this other behavior that we report in this paper, we can make the difference in providing a better environment for dealing with the symptoms of autism. If that’s what the problem that this teenager has, it is never too late to intervene. This is actually based on experience but also based on neuroscience. The brain fortunately still can be modified late in life, not to the same extent that it can be modified in early life for sure, but it can be modified. You never lose the capacity to make a positive change.

Now the downside of that he said that’s a reason why FMRP deficiency, which is the fundamental problem Fragile X has, this is a lifelong situation because you need the therapy all the time for your connections in the brain to function properly. But, the good side is that the connections are constantly being reorganized and being in some way fine-tuned, is that it’s always a window of opportunity. So when we do come up with a better treatment for Fragile X we know that even though the trial was done in young children we still know that drug may be able to work to some extent in someone who’s older.

Well I would agree with you, and I’ve seen that. I mean, I think it’s never too late, and I think that I’ve got that myself, an adult son, and he continues to learn and he continues to understand my kind of repercussions of his behavior, so I think that, like all of us do, I think we all continue to learn our whole life and that’s true for our kids too.

So with that, Walter, I think we’ll end on that question and I would like to say thank you very much for sharing your expertise with us. It was very interesting and informative. This was the first webinar we’ve had that really discussed autism and Fragile X, so thank you very much.

I am glad I had the chance to cover this a very important topic on Fragile X.


Fragile X Syndrome & Autism »
When associated with FXS, autism is caused by the genetic change or mutation in the Fragile X gene—the most common genetic cause of autism.

A Blood Test for Autism? Not so Fast »
The notion that autism itself can be directly diagnosed through a blood test is incorrect and misleading.

Autism Spectrum Disorder in Fragile X Syndrome: Cooccurring Conditions and Current Treatment »
This study examines the impact of the ASD diagnosis in a large clinic-based FXS population to better inform the care of people with FXS. (Pediatrics, June 2017, Vol. 139)

More About Dr. Kaufmann

Dr. Walter KaufmannWalter E. Kaufmann, MD
Director, Center for Translational Research, Greenwood Genetics Center, South Carolina

Born in Santiago, Chile, Dr. Kaufmann, a graduate of the University of Chile School of Medicine, is currently a senior associate neurologist at Boston Children’s Hospital. Throughout his distinguished career, he has also enjoyed faculty appointments at his alma mater as well as the Johns Hopkins University School of Medicine, Harvard Medical School, and the Massachusetts Institute of Technology. He was the recipient of a Honorary degree from Harvard Medical School in 2013.

His research interests have focused on neurodevelopmental disorders including Fragile X and Rett syndromes. Dr. Kaufmann is extensively published in the medical literature and has been funded through numerous major grants from the National Institutes of Health (NIH), industry, and academia. He has served as editorial peer reviewer for over 90 scientific journals.