EDS 101

What Is Ehlers-Danlos Syndrome?

Ehlers-Danlos syndrome is a genetic condition that affects connective tissue — the material that gives your body its structure, support, and resilience. Because connective tissue is found throughout the body — in joints, skin, blood vessels, muscles, and nerves — EDS doesn't affect just one place. It can influence how many different systems work, and how they communicate and respond to stress.

EDS is not a single diagnosis. It's an umbrella term for 13 recognized subtypes, each with its own pattern of symptoms. For most subtypes, the genetic cause traces back to differences in how collagen is made, processed, or assembled — which is why understanding collagen, as described in the previous section, provides such an important foundation for understanding EDS as a whole.

Hypermobile EDS is the most common subtype, accounting for the majority of people diagnosed with EDS. Unlike most other subtypes, no consistent collagen gene mutation has yet been identified in hEDS — which has led researchers to look more carefully at what else might be driving it.

What is joint hypermobility?

Normally, our musculoskeletal system is designed to maximize function while minimizing injury. When ligaments don’t resist tension as they should, when resting muscle tone is poor, or when joint sockets are shallower than they should be to tolerate a particular mechanical load, this can result in joints that move more than they safely can move. Without symptoms, this is considered an anatomical variant and someone might just be described as “flexible.” When the body sends pain signals to the brain, it requires attention as continued misuse will likely result in undesirable symptoms.

What is collagen?

Collagen is the name of the protein that forms the building blocks of connective tissue and gives it structure and strength. Its intended purpose is to resist deformation while providing a matrix for support of tissues like skin, blood vessels, tendons/ligaments and as scaffolding or protection of internal organs. When it is not working as intended, skin stretches and breaks easily, wounds don’t heal well, blood vessel walls are weak and rupture or cause excessive bruising, tendons and ligaments are too elastic and “sprain” or easily “tear” and internal organs move around too much and “prolapse” or “herniate.”

More than just a collagen problem — in hEDS specifically

That search has led somewhere important. Recent studies examining genetics, immune function, and protein activity in people with hEDS have produced compelling early evidence that the body may have changes in the pathways that regulate immune response, inflammation, and stress signaling. This suggests that for hypermobile EDS, the picture may extend beyond connective tissue structure alone — the immune system itself may be dysregulated, keeping the body in a more reactive, more sensitized state much of the time.

It's important to be clear that this is an active and evolving area of research. Whether immune dysregulation is the primary driver of hEDS, a contributing factor alongside connective tissue differences, or one of several possibilities still being explored — that remains an open question. What the research does suggest is that hEDS is more complex than a single structural defect, and that understanding it fully will require looking at multiple interacting systems.

This complexity helps explain something that many people with hEDS already know from lived experience: the symptoms don't stay in one place. Frequent pain flares, allergy-like reactions, fatigue that feels out of proportion to what you've done, dizziness, and heart rate changes aren't random or unrelated. They may all be reflecting the same underlying picture — one where connective tissue differences, nervous system regulation, and immune signaling are all interacting with each other.

Why this matters

Understanding EDS as a whole-body condition — not just a joint problem — changes how we think about symptoms and care. It explains why symptoms can feel widespread, unpredictable, or hard to pin down. And it's a big part of why physical therapy for hEDS needs to be individualized and carefully paced, rather than based on programs designed for a different kind of body.

Your body isn't overreacting. It's responding exactly the way a body with hEDS responds. We'll cover what that means for treatment in detail later in this book.

What is Hypermobile EDS?

Hypermobile EDS (hEDS) is an inherited disorder of connective tissue and its collagen protein. It is defined as a syndrome by the association of the following conditions that tend to occur together: generalized joint hypermobility, joint instability complications, systemic musculoskeletal pain, and unique skin features. It may also include pelvic dysfunction, cardiovascular symptoms, autonomic nervous system dysregulation, anatomical variants, GI dysfunction, difficulty with balance, anxiety and/or mast cell activation syndrome. Research is beginning to demonstrate that these other conditions are linked to hEDS and not just arising independently. The prevalence of hEDS is estimated to be 1 in 5000 people. Although suspected to have a genetic marker associated with the expression of hEDS, one has not yet been identified. 

In plain language: Collagen is the material my body uses to hold itself together — and in most forms of EDS, differences in how collagen is built help explain why joints feel unstable, why skin behaves differently, and why symptoms show up in so many places at once. For hypermobile EDS specifically, researchers are finding that the picture may involve more than collagen alone — with immune and inflammatory pathways potentially playing a role as well. That's actually encouraging news, because it means science is getting closer to understanding what's really happening. The more researchers understand, the better care can become.

Sources for this section:

• Mao JR & Bristow J. The Ehlers-Danlos syndrome: on beyond collagens. J Investig Dermatol Symp Proc. 2001.

• Chiarelli N, et al. Cellular and molecular mechanisms in the pathogenesis of EDS. Front Genet. 2019.

• Malfait F, et al. The Ehlers-Danlos syndromes. Nat Rev Dis Primers. 2020.

• Miklovic T, et al. Ehlers-Danlos Syndrome. StatPearls. 2023.

• Ritelli M, et al. Molecular genetics and pathogenesis of Ehlers-Danlos. Front Genet. 2020.

• Ricard-Blum S. The collagen family. Cold Spring Harb Perspect Biol. 2011.

• Shoulders MD & Raines RT. Collagen structure and stability. Annu Rev Biochem. 2009.

• Gensemer C, et al. Hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders: Clinical and genetic update. Am J Med Genet C Semin Med Genet. 2020.

• Malfait F, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017.

• Fajardo-Jiménez MC, et al. Epidemiology and clinical characteristics of hypermobile Ehlers-Danlos syndrome. Orphanet J Rare Dis. 2022.

• Demirdas S, et al. Insights into the genetic basis of hypermobile Ehlers-Danlos syndrome. J Med Genet. 2022.

• Mao J, et al. Genetic complexity and multisystem involvement in hypermobile Ehlers-Danlos syndrome. J Med Genet. 2020.

• Griggs RC, et al. Proteomic profiling reveals immune and inflammatory pathway alterations in hypermobile Ehlers-Danlos syndrome. Front Immunol. 2025.

[Please note: Wendy4Therapy is not a medical doctor and is not licensed to provide an official medical diagnosis. Education provided here is for your information only, and it is expected that you visit a medical practitioner who is licensed to provide a diagnosis for further exploration. Wendy4Therapy can take you through the diagnostic criteria but cannot formally diagnose EDS or related conditions. Please do  not reproduce without permission. This is GENERAL and not intended to be customized for individual patients. Please follow consultation and recommendations of your healthcare provider for specifics to your condition.