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Current Approaches to the Management of Rett Syndrome

  • Authors: Jeffrey Neul, MD, PhD; Dallas Armstrong, MD
  • CME / ABIM MOC Released: 11/11/2022
  • Valid for credit through: 11/11/2023
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  • Credits Available

    Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 0.25 ABIM MOC points

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Target Audience and Goal Statement

This activity is intended for neurologists, pediatricians, and primary care physicians.

The goal of this activity is for learners to be better able to effectively manage patients with Rett Syndrome.

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Management goals of Rett syndrome


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  • Jeffrey Neul, MD, PhD

    Professor of Pediatrics, Division of Neurology, Pharmacology, and Special Education
    Annette Schaffer Eskind Chair and Director
    Vanderbilt Kennedy Center
    Vanderbilt University Medical Center
    Nashville, Tennessee


    Jeffrey Neul, MD, PhD, has no relevant financial relationships.

  • Dallas Armstrong, MD

    Assistant Professor
    Department of Pediatrics and Neurology
    UT Southwestern Medical Center
    Dallas, Texas


    Dallas Armstrong, MD, has the following relevant financial relationships:
    Research funding from: Taysha Gene Therapies (former)


  • Pakinam Aboulsaoud, PharmD

    Senior Medical Education Director, Medscape, LLC


    Pakinam Aboulsaoud, PharmD, has no relevant financial relationships.

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    Associate Director, Accreditation and Compliance, Medscape, LLC


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Current Approaches to the Management of Rett Syndrome

Authors: Jeffrey Neul, MD, PhD; Dallas Armstrong, MDFaculty and Disclosures

CME / ABIM MOC Released: 11/11/2022

Valid for credit through: 11/11/2023




Jeffrey Neul (00:01):

Hello, I'm Dr Jeffrey Newell, the director of the Vanderbilt Kennedy Center and Professor of Pediatrics, pharmacology and special education at Vanderbilt University Medical Center in Nashville, Tennessee. Welcome to this podcast series titled, Bringing Focus to the Diagnosis and Management of RETT Syndrome. Today. Joining me is Dr Dallas Armstrong. Dr Armstrong, could you introduce yourself please?

Paige Nues (00:29):

I am the medical director of the RETT and Related Disorders Clinic here at Children's Health in Dallas, Texas and an assistant professor at the University of Texas Southwestern in Dallas.

Jeffrey Neul (00:41):

Welcome, Dallas. And thank you for joining me and us today. Today we're going to talk about this episode, today's titled, Current Approaches to the Management of RETT Syndrome. So let's begin a little bit with background. Dallas, could you tell me a little bit about what are the clinical features of RETT syndrome?

Paige Nues (01:09):

Rett syndrome is characterized by early, apparently normal development, and a period of regression. And in that period of regression, individuals will lose skills they once had with their hand use, with language, with walking, and there's often this very characteristic, repetitive hand movement that happens around the time of that regression.

Jeffrey Neul (01:52):

Okay. So what I understood is that essentially they're having a normal development and then they lose some skills, some hand skills, they lose some spoken language skills, I have trouble walking. And then they have these repetitive hand movements, this loss of these skills and this initial onset about what kind of age does that happen?

Paige Nues (02:17):

And we often see the regression sometime after six months and before age five years. And often most girls we're seeing that more in those toddler years. When we start to see the regression and it often happens around the same time that those hand movements start to occur.

Jeffrey Neul (02:33):

Do people lose both the hand skills and the spoken language at the same time always? Or is it sometimes disconnected?

Paige Nues (02:45):

Certainly the latter and each child's experience with that regression is unique and important for families to try to ride out. We're really trying to optimize development, so as they go through that regression, we want to hold onto any skills that we can creatively and then rebuild as possible after that regression period has ended.

Jeffrey Neul (03:09):

So the regression period does end and what happens after that?

Paige Nues (03:14):

Just after that development continues, new skills are learned, but the pace of that skill acquisition is often slower than neuro typical counterparts. And so part of what we hope for these individuals is that their care team can circle around them and really support the acquisition of new milestones along the way.

Jeffrey Neul (03:36):

Do people with RETT syndrome have other problems the other than this loss of skills and this trouble with the walking and hand use and spoken language?

Paige Nues (03:48):

And they're very important to quality of life for individuals with RETT syndrome. So I think it's important to talk about all these different body systems that are affected in this diagnosis. When I talk to families, so often, one of the more pressing things that we talk about in a neurology visit is things like GI, their gastrointestinal system. This is kind of sweeping. They can have reflux, they can have really troubling constipation issues, there can be difficulties with feeding themselves and also taking food that's given to them by mouth. Meal times can last a very long time and certainly we can struggle to get enough nutrition by mouth. And so that's a really important component of their care. Certainly there's also this very unique abnormal respiratory pattern that can be very important for individuals with RETT syndrome. There can be pauses in breathing, there can be breath holding, air swallowing, and this quick breathing event that's sometimes worries some procedure as well.


They can do abnormal movements outside of seizures And also these girls are certainly at risk for seizures and so their clinical care becomes a little bit murky. It becomes very important to tease out which body system is causing the problem at hand and how to support that. Certainly it's also worth talking about musculoskeletal issues. Individuals with RETT syndrome are at risk for scoliosis. They also can have cardiac abnormalities that aren't persistent over time. Sometimes they can come and go. And so investigating that with cardiac electrophysiology studies is a really important part of caring for them as well.

Jeffrey Neul (05:28):

You mentioned a number of things and you mentioned seizures, you indicated that they may be common in RETT syndrome?

Paige Nues (05:39):

Yes, and one of the things that I think is encouraging when we're thinking about treating the seizures in RETT syndrome is sometimes we can be really thoughtful about the medications we use to protect individuals from seizures. Sometimes those medications can have other effects that support, let's say mood individuals with RETT syndrome certainly can also struggle with anxiety. There are mood stabilizing seizure medications we can use, and also the breathing abnormalities that can be very troubling for some families or the teachers that take care of these individuals. Some of our seizure medications can reduce the frequency of those breathing abnormalities as well. So we're using a medication maybe primarily for seizures, but we're hoping to get some other benefits from it as well.

Jeffrey Neul (06:26):

What I understand is that there's a number of different systems and issues, clinical problems that can arise in RETT syndrome. You had already sort of indicated that regression period was in the toddler a year and a half, two and a half kind of range oftentimes. But what about these other things like seizures? Is that off? Is that also happening at two years old or is that something that people have to watch for later and some of these other issues you mentioned? I mean, when do they happen in the course of this child's lifetime?

Paige Nues (07:06):

A really helpful question to think about. There's actually a consensus guideline on managing RETT syndrome across the lifespan. That I think is a lovely resource when thinking about this because you know can think about in the first five years and in the early elementary years and once we talk about puberty and individuals with RETT syndrome. But I think it's important to talk about the GI symptoms we talked about, are very early on, something that children are dealing with right around that time when they're getting diagnosed or hopefully getting diagnosed around the time of their regression. Seizures definitely can present in those early days, but sometimes that difficulty can present more throughout childhood and certainly things like scoliosis or even more of a prominent concern near adolescence and in young adulthood. And then the, RETT episodes and the breathing abnormalities that we discussed, those are something that seem to come up throughout the course of people's lives with RETT and something that can be variably problematic for people.

Jeffrey Neul (08:16):

So I mean since there are these variety of things then they seem to have different potential onsets. How does that sort of influence how you start thinking about what your goals are, treatment and what the therapeutic plan over time, how it evolves?

Paige Nues (08:34):

Yeah, I think early on really focusing on screening for any seizures, making sure that those aren't going undetected early on is really important. Optimizing as much as we can for expressive communication turns out to be something that can help with anxiety down the road. As these individuals become more and more aware of the world around them, the better we can be at helping them express their wants and desires can help reduce some of that frustration and some of those anxiety exacerbations. And then I think for some of those other health issues, scoliosis, constipation, EKG abnormalities, there's certainly also tone abnormalities that could be low tone, that could be abnormal tone. I think having a checklist for myself, as I'm seeing these individuals, really helps to make sure that I'm screening for things like scoliosis and cardiac abnormalities at each yearly visit to make sure that too much time doesn't elapse without having intervened on those issues if they exist.

Jeffrey Neul (09:42):

Well it sounds like because there's so many different systems, thinking about a care team, at a place like a RETT center, what is the sort of componentry that is helpful to have other parts of the care team?

Paige Nues (10:00):

Yes, I think it's really important that people with RETT syndrome have specialists on their team who are passionate about caring for people with RETT syndrome. So certainly you want a gastroenterologist on the care team. Often there's a sleep medicine doctor who helps. We haven't mentioned that yet, but certainly individuals with RETT syndrome can have altered sleep, both sleep onset insomnia and sleep maintenance difficulty, and an orthopedist who can help us with scoliosis. Certainly physical medicine and rehabilitation teams are really important for optimizing all of the gait and occupational hand use and also thinking about bracing if that's ever something that children need. And then additionally, the cardiology department has been really important for us. We definitely do the EKGs, but sometimes children benefit from Holter monitors as well as it gets some longer term data. And then we also have, I think it's important that physical therapy, occupational therapy, speech therapy, are all involved.


Many individuals will benefit from their state school for the blind and visually impaired. There could be a component of cortical visual impairment and really understanding that can help inform the way any augmented communication device is structured to help individuals be even more successful in trying to utilize that technology to help them express themselves to the world outside. And also sometimes supports like school services are really important to help advocate for the needs of these young children and their schools. And lastly, I think it's really important when we're able to connect families of people with RETT syndrome, with other families through some of the national organizations and even local chapters. I found that to be very, very helpful for families. And sometimes I joke is the most important thing I do at our first visit.

Jeffrey Neul (11:58):

Yeah, absolutely. You work at a center, a recognized center of excellence where you have a lot of people with experience and people you can call on. Give any advice or places people can look if they are a practicing pediatrician or child neurologist and a place that it doesn't have a center, but they want to have some advice or guidance to think about what they should be doing in terms of health maintenance and medical evaluations.

Paige Nues (12:38):

I appreciate this question a lot and I think going back to one of the resources that I mentioned earlier, I think that the consensus guidelines on managing RETT syndrome is a very helpful document complete with some checklists about the frequency of screening. And I also think it's important for people to know that if they look at the International RETT Syndrome Foundation website and look at the centers of excellence that are listed there, any of those medical directors are also going to be happy to field questions and provide support as people are caring for individuals with RETT syndrome who aren't close to a center of excellence.

Jeffrey Neul (13:16):

Yeah. Great. Do you have any further comments or pieces of advice you'd like to give?

Paige Nues (13:25):

Yes, I think I initially underestimated how important optimizing expressive communication was in individuals with RETT syndrome. And it's an uphill battle often to obtain the technology that's needed and do all of the therapy. People with RETT syndrome follow the whole bell curve of personality. So some individuals are going to be like me and quite stubborn and so it can be an uphill battle to get those augmented communication devices set up. But it has been one of the more fulfilling parts of my career thus far to watch people start to be able to use that device as a window to let the outside world in and to share what they're thinking and seeing the Rett episodes decrease, seeing the constipation improve, seeing the respiratory dysrhythmia events decrease with that has been a very fulfilling experience.


And I would also add that in individuals who need an anti-seizure medication, really thinking about, can I get two for one benefit with the medication I'm using is a really important part of treating people with RETT syndrome. So thinking about medications with carbonic andradites activity, for instance, to really help if respiratory dysrhythmia or red episodes are a significant piece of that particular patient's experience with RETT syndrome are using mood stabilizing medications if the anxiety piece is a particularly difficult part of their journey.

Jeffrey Neul (15:05):

Excellent. So I think that the key takeaway that we have from this is that RETT syndrome is a complicated disorder with many different clinical and overall features that impact the quality of life of people who are affected. And it's important to recognize that these things come at different times and likely need different specialists to engage with. But there are published guidelines on clinical care that provide some guidance and checklists of things to monitor for people who are affected. So Dallas, I'd like to thank you for this great discussion today. I'd like to thank everyone for participating in this activity and please continue on to answer the questions that follow and complete the evaluation.