Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common forms of muscular dystrophy, affecting individuals across the lifespan with variable severity. Advances in genetic understanding and therapeutic development have led to an era of promising disease-modifying strategies.

In this episode, Katie Grouse, MD FAAN, speaks with Renatta N. Knox, MD, PhD, author of the article "Facioscapulohumeral Muscular Dystrophy" in the Continuum® October 2025 Muscle and Neuromuscular Junction Disorders issue.

Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California San Francisco in San Francisco, California.

Dr. Knox is an assistant professor of neurology in the Division of Pediatric Neurology and Neuromuscular Section at Washington University School of Medicine in St. Louis, Missouri.

Additional Resources

Read the article: Facioscapulohumeral Muscular Dystrophy

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 Full episode transcript available here

Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast.

Dr Grouse: This is Dr Katie Grouse. Today I'm interviewing Dr Renatta Knox about her article on fascioscapulohumeral muscular dystrophy, which appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders. Welcome to the podcast, and please introduce yourself to our audience.

Dr Knox: Hi Katie, thank you so much for the invitation for the audio interview. I'm looking forward to our conversation. As she mentioned, my name is Renata Knox. It's a pleasure to be here today.

Dr Grouse: I'd like to start by asking, what is the key message that you hope your readers will take from your article?

Dr Knox: I would say two things. The first is an appreciation and understanding of the unique genetic mechanism that leads to FSHD. And the second is the really exciting therapy landscape that we find ourselves in. So, we're hopeful that there will actually be disease-modifying therapies for FSHD soon.

Dr Grouse: We're really looking forward to learning more about that. Now, before we get to that piece, could you just remind us of the clinical manifestations and features that are specific to FSHD?

Dr Knox: So, one of the most unique things about FSHD that we see clinically is the pattern of weakness. So, one of the first features is that it's asymmetric. And then there are certain muscle groups that typically are affected, and that's partly where the name comes from. So, we see effects in the face, the limbs, the trunk; and so, those are some of the unique features that we see clinically.

Dr Grouse: I'd love it if you could walk us through how you approach diagnosing a patient who presents with proximal weakness where FSHD is in your differential.

Dr Knox: Yeah, it's a really great question. So, I would say it depends. So, I actually focus on FSHD in my clinical practice. So, many times patients are referred to me because there's a very high suspicion or there's a known family history of FSHD. So, that's one category of cases. I would say the other category of case is where it's, as you said, maybe more proximal weakness more broadly. Someone that's before me who has a known family history, they really have some of the characteristic physical features---which I'm pretty attuned to, as this is, you know, part of my subspecialty---I'll actually go directly to FSHD genetic testing. And that is one of the unique features of this disease, that the next-generation sequencing panels that are typically used for some of our other muscle diseases, FSHD is not captured on those. So, we actually have to send targeted testing for FSHD to diagnose it. So, that is one category where, again, I have a very high suspicion either based on their clinical presentation and/or a known family history, then I will actually go directly to FSHD-targeted genetic testing. In the second case, where it is one of the conditions that I'm considering among others, I will do more broad testing. So, I will get a CK level to see if there's evidence of muscle breakdown. I'll likely also do one of the next-generation sequencing panels that we have access to, which will allow us to identify, potentially, one to two hundred potential muscle diseases. And then again, if FSHD is higher on my differential in that second group of patients, then I will also send targeted FSHD-specific testing.

Dr Grouse: That's really helpful. And I'm wondering if you have any thoughts about common pitfalls that you've seen when providers are trying to work this up?

Dr Knox: I don't know if I would say pitfalls. I think I would acknowledge that it's challenging. My subspecialty training in neuromuscular medicine and also gene therapy. And so FSHD is pretty high on my radar. But I would say in neurology in general---and then, you know, the general medical population---,it really isn't something t