Scott Webb (Host): Hypermobility spectrum disorder, or HSD, is a connective tissue disorder that causes joints to be more flexible than normal and can lead to pain and instability for kids. And my guest today is here to explain HSD, how it relates to Ehlers-Danlos Syndrome, and more.

I'm joined today by Dr. Mekhla Varma. She's a pediatrician with Stanford Medicine Children's Health. This is Health Talks from Stanford Medicine Children's Health. I'm Scott Webb. Doctor, welcome to the podcast.

Mekhla Varma, MD: Thank you so much for having me here.

Host: Yeah, it's my pleasure to have you here. I'm going to learn from you today, because I just don't know a lot about hypermobility spectrum disorder, maybe easier said as HSD. So, let's start there, Doctor. What is it and how widespread is HSD?

Mekhla Varma, MD: Hypermobility disorders are disorders whose primary manifestation is generalized joint hypermobility, that is the ability to move the joints beyond typical ranges of motion. This can result in pain, instability, muscle strain, postural faults, and other musculoskeletal complications. Hypermobility disorders are not limited to hypermobile joints. They are multisystemic, which means that they can and do affect multiple organ systems. Connective tissue is everywhere in the body, so the impact the syndrome has can show up in a lot of different ways and it can also change with time.

The prevalence of hypermobility disorders is estimated to be one in 600 to one in 900. However, the exact prevalence of HSD and hypermobile Ehlers-Danlos syndrome, which is HEDS, is not well established. This is because a lot of people are not diagnosed or it takes multiple years to get diagnosed. And the disorder is often underdiagnosed because of lack of clinician familiarity and experience. There also is no confirmatory genetic testing as yet for HSD, which is hypermobility spectrum disorder.

And one of the most difficult things about HSD is that the presentation clinically can differ very much between patients. So, to be honest, we really do not have the exact prevalence, but go with one in 600 to one in 900.

Host: right. So actually, you know, one in 600 or one in 900, you know, is a little more common than I thought it was. And as you say, it is a lot to take in here, but underdiagnosed. And I know that it's a relatively new diagnosis, so when was it first classified as a separate condition, and why?

Mekhla Varma, MD: People have been speaking of hypermobility since the 1930s, when the first few cases were documented. And over time, newer cases were found and documented. There were several classifications that happened. And in 2019, the classification for Ehlers-Danlos syndromes came out in which they made the criteria for diagnosis very strict. A lot of people who had joint hypermobility did not fit all the criteria for hypermobile Ehlers-Danlos syndrome, which is HEDS. And therefore, the category of HSD, which is hypermobile spectrum disorders, was created to include all those people who had hypermobility, and all the other comorbid conditions that went with it, however, did not meet the strict criteria, which were formulated. This is something that is undergoing revision again, so we might have different classifications and different criteria in the next few months from what we understand.

Host: Yeah. It does seem like HSD is really a bit of a work in progress, if you will, and I know that it's commonly associated with other genetic conditions, like, as you say, Ehlers-Danlos syndrome, EDS. But how is HSD different from EDS?

Mekhla Varma, MD: The underlying issue is hypermobility, which is the common thread between HSD and EDS, the hypermobile type of EDS. However, there are very many overlapping morbidities, which need to be understood. It's not just about calling a disorder a particular name. The HEDS criteria were made stricter so that we had a clearer way of identifying HEDS; however, all those people who did not meet the criteria, they also needed clinical care. And to me, as a clinician, these are just names where some patients meet criteria and some people do not meet criteria. However, the care that they need is very similar. And also, it does not mean that if you're not meeting the criteria for hypermobile EDS, you are less affected because there can be very many manifestations, which are not a part of the HEDS criteria, which are still important to treat and manage.

Host: Yeah, I want to talk about the symptoms and complications. I know that joint laxity itself can cause sprains, strains, dislocations, you know, the greatest hits, if you will. But what are some of the other symptoms and complications that are associated with HSD?

Mekhla Varma, MD: So, the most common comorbid conditions, which are associated with HSD in children are chronic pain, functional gastrointestinal disorders, chronic fatigue, functional bladder disorders, dysautonomia, and anxiety. However, there can be a lot more symptoms, which can happen because connective tissue is everywhere. It can extend from, you know, easy bruising to poor wound healing and then stretchy and soft skin. There's also data, which is talking about more ADHD in kids who are hypermobile.

Host: It's so great to have you here today, doctor, your expertise, your compassion, your way of explaining things. I'm trying to stay with you here. It's a lot to take in, probably more than we can cover in a podcast, but we'll at least sort of get the headlines out and cover the broad strokes, if you will. Maybe the $64,000 question for those old enough to know what that means and get that reference, doctor, is there a treatment or cure for HSD?

Mekhla Varma, MD: At this time, no. We try to manage all the clinical manifestations of HSD individually. For instance, for people who are getting chronic injuries to their joints because they're hypermobile, we make sure that they get adequate physical therapy. We talk about, you know, surgeries which are sometimes required to stabilize the joints. They treat the gastrointestinal manifestations of the disease as separate entities. So, unfortunately, there's no one cure for HSD as of now. We are still learning so much every single day. At some point, hopefully, we can identify the exact pathogenesis of HSD and find a targeted cure.

But until then, I want to say that the important thing to remember is that we need to be able to identify the disorders which are associated with hypermobility, whether they are bladder disorders, whether they are gut disorders, whether they're anxiety, depression, and manage each one of these disorders individually. And that's why one of the most important things in hypermobility is to have a team of doctors who can help. You need one primary care clinician who can understand and identify the disorder, understand the comorbidities of the disorder, and then engage other specialists in taking care of the individual issues.

Host: Yeah. You must have read my mind, I was just going to ask you, you know, what types of doctors care for HSD patients and do you personally make referrals? It sounds like you do. Depending on the type of problems that a child has, it seems like it really might be a multidisciplinary group of physicians and specialists that might help kiddos.

Mekhla Varma, MD: That's correct. I was listening to one of the very well-known figures in hypermobility, Dr. Francomano. And she mentioned in her talk that when we were medical students, one of the things which was told to us was if it's multisystemic, if every system is involved, it's probably nothing.

And that just couldn't be more untrue in the case of hypermobility. So, it is important for clinicians to understand that there can be manifestations of the disorder in every single system, and then identify the issues one by one and handle them. And sometimes, as clinicians, it's not easy to manage every single problem at the same time. So, we direct our energy and attention towards those problems, which are and they are truly impacting a patient's quality of life and then gradually manage everything else. And of course, there's an underlying need to make lifestyle changes a lot of times in hypermobility disorders, which impact all the comorbidities in a positive way.

Host: Yeah, kind of like with a mechanic, doctor, you know, when you take your car and they don't just immediately replace the engine. You know, they start with the smaller things that they can handle immediately and they work their way towards the bigger things. So, I get your point that there is no magic pill or cure for HSD and you get this group of specialists, multidisciplinary specialists, involved in communicating and trying to help kids and tackle things as best they can, sometimes one at a time, sometimes maybe more. Really interesting stuff today, really educational. I just want to give parents a chance as we wrap up here, doctor, like what should they look for if they suspect that their child is more flexible than others?

Mekhla Varma, MD: I would say talk to your pediatrician first. It's the first place where you can find information and the important thing about identifying hypermobility in your child is to make sure that the excessive range of motion in their joints does not have them get microtraumas, which can accumulate over time and lead to big joint issues. So, children who are hypermobile need to learn how to use their joints so that they don't damage them. And physical therapy plays a huge role here. So, talk to your doctor. A great resource for parents on hypermobility is the Ehlers-Danlos Society. They have a wealth of information online for patients, for doctors, and I think it's a great place to start if you suspect that your child may be hypermobile.

Host: Yeah. That sounds right to me. Well, as I said, doctor, I really appreciate your time and your expertise. I learned a lot today. I feel like there's a lot more I need to learn about HSD as it does appear, as you say, this is just a big work in progress and there could be new and more and exciting developments in the coming months or years, certainly hope so for patients and their families. I just really appreciate your time. Thank you so much.

Mekhla Varma, MD: Thank you so much for having me here.

Host: Yeah, it's my pleasure. And for more information, go to stanfordchildrens.org. And we hope you found this podcast to be helpful and informative. If you did, please share it on your social channels and be sure to check out the full podcast library for additional topics of interest. This is Health Talks from Stanford Medicine Children's Health. I'm Scott Webb. Stay well, and we'll talk again next time.