What is Hypermobile Ehlers-Danlos Syndrome (hEDS)?

Hypermobile Ehlers-Danlos Syndrome (hEDS) is one of 13 types of Ehlers-Danlos Syndromes (EDS), a group of connective tissue disorders that affect collagen and other extracellular matrix proteins that are responsible for giving our skin, joints, and blood vessels strength and flexibility [1]. hEDS is a complex and often misunderstood condition. Unlike other types of EDS, hEDS does not have a known genetic marker, which makes diagnosis particularly challenging [2].

hEDS is mainly characterised by joint Hypermobility, joint instability, pain and other body-wide symptoms. Joint instability means your joints move beyond the typical range of motion; that you are “double-jointed” or extra bendy. Hypermobile Ehlers-Danlos Syndrome (hEDS) symptoms and signs vary, meaning that it often mistaken for other diagnoses.

If you or someone you know has been diagnosed with hEDS, or if you suspect you might have it, getting a diagnosis and understanding the condition are the first steps in managing its effects on daily life.

Types of Hypermobile Spectrum Disorders (HSD) and Hypermobile Ehlers-Danlos Syndromes (hEDS)

Starting in March 2017, a new classification system was established by the International Consortium on the Ehlers-Danlos Syndromes[3].  The Consortium highlighted a new diagnostic term of Hypermobility Spectrum Disorder (HSD) for those who don’t meet the hEDS criteria (or any other Heritable Disorder of Connective Tissue (HDCT)).

This new classification included a review of Hypermobility disorders, with Hypermobility syndrome now renamed and categorised under the umbrella of Hypermobility Spectrum Disorders. The spectrum of joint Hypermobility now includes:

• Generalised Hypermobility Spectrum Disorder (G-HSD)
• Peripheral Hypermobility Spectrum Disorder (P-HSD)
• Localised Hypermobility Spectrum Disorder (L-HSD)
• Historical Hypermobility Spectrum Disorder (H-HSD)
• Hypermobile Ehlers-Danlos Syndrome (hEDS)

How common is hEDS, and how does it relate to Hypermobility?

hEDS is the most common type of EDS, making up about 90% of cases. It is a genetic condition that affects connective tissues, leading to overly flexible joints, joint problems, and long-term pain. Research shows that around 10% of people with generally flexible joints have symptoms severe enough to be diagnosed with Hypermobile Spectrum Disorder (HSD) [4].

More recently, experts have started to see hEDS and HSD as part of the same condition rather than completely separate disorders. New estimates suggest that up to 1 in 500 people may have hEDS or HSD, which is much more common than earlier estimates of 1 in 5,000[5]. This means many people with Hypermobility-related conditions are far more common than once believed and that many people may go misdiagnosed or not be diagnosed.

If you’re navigating life with hEDS, understanding its complexities can help you advocate for better care and support. While there’s still much to learn, increasing awareness and research are shedding new light on this often-overlooked condition.

When it’s more than just being bendy – Understanding Hypermobility Syndromes, Hypermobile EDS and the overlap

While many people with Hypermobility do not experience any problems, others may face significant health challenges. When Hypermobility is accompanied by symptoms such as pain, frequent injuries, fatigue, joint instability, and other symptoms, it is referred to as Symptomatic Hypermobility. When these symptoms significantly impact daily life, Hypermobility is then termed “syndromic” or “symptomatic” [6]. The two primary conditions associated with symptomatic hypermobility are Hypermobile Spectrum Disorder (HSD) and Hypermobile Ehlers-Danlos Syndrome (hEDS) [7].

In reality, everyone with Symptomatic Hypermobility who falls within this hEDS/HSD/JHS group requires similar symptom-based treatment and management, with the awareness that there could be a connective tissue disorder present.

The Hidden Links:  How Heritable Connective Tissue Disorders (HCTDs) overlap and share symptoms:

• Ehlers-Danlos Syndromes (EDS) – Different types have different prevalences (how many people have this condition in the total population). The most common, Hypermobile EDS (hEDS), may affect 1 in 500 people, while rarer types, like vascular EDS, occur in about 1 in 50,000 to 1 in 200,000
• Marfan Syndrome – Affects about 1 in 5,000 people worldwide.
• Loeys-Dietz Syndrome (LDS) – Considered rare, affecting around 1 in 100,000
• Osteogenesis Imperfecta (OI) – Varies in severity, with an estimated prevalence of 1 in 15,000 to 1 in 20,000

Hypermobile Ehlers-Danlos Syndrome (hEDS) symptoms

Individuals with hEDS may experience a variety of symptoms, which can vary widely among individuals [8].

Here are some common symptoms and conditions associated with hEDS:

• Joint Hypermobility *: Joints that move beyond the normal range of motion (hyperflexible joints).
• Chronic joint pain and instability: Frequent strains, joint subluxations, dislocations, sprains, and chronic pain.
• Muscle pain*: Generalised muscle pain and weakness.
• Skin differences *, soft, stretchy, may including bruising and poor wound healing: Skin that is soft, velvety, and may be slightly stretchy and may not heal properly.
• Fatigue*: Extreme tiredness and low endurance, waking without feeling rested.
• Digestive problems/Gut issues *: Issues such as heartburn, diarrhoea, constipation, gastroparesis, and gastroesophageal reflux disease (GERD)and bloating.
• Headaches
• Anxiety and or depression*
• Dizziness and increased / racing heart rate: Especially after standing up.
• Problems with internal organs and or blood vessels*: Such as mitral valve prolapse, or organ prolapse.
• Bladder/Urinary issues: Difficulty controlling bladder functions.
• Dysautonomia/Autonomic dysfunction: Issues with blood pressure regulation and other autonomic functions, including postural orthostatic tachycardia syndrome (POTS)
• Dental issues*
• Female health concerns
• Sleep difficulties
• Neurodivergence is when there is a natural difference in how people think, learn, and process information. It includes conditions like autism, ADHD, dyslexia, and others.
• Slow to reach developmental milestones [9]: Children with HSD or hEDS can experience delayed motor development and poor coordination

The symptoms listed above with a * next to them also can relate to other more complex types of EDS, or connective tissues disorders, so these need exclusion prior to a hEDS diagnosis. Full diagnosis outline is below.

It is important to note that not everyone with hEDS will experience all of these symptoms, and the severity can vary widely between people and within the same person over time.

Causes of Hypermobile Ehlers-Danlos Syndrome (hEDS)

The exact cause of hEDS is not fully understood, but it is believed to be a genetic disorder[2]. Unlike other types of EDS, which are often linked to specific genetic changes, the genetic basis of hEDS remains hidden. However, it is known that hEDS tends to run in families, meaning that if a parent has hEDS, there is a 50% chance their child will inherit it.

Research has shown that hEDS is associated with abnormalities in collagen, a protein that provides structure and strength to connective tissues. Collagen abnormalities can lead to the characteristic symptoms of hEDS, such as joint Hypermobility and skin elasticity.

What is Collagen?

Collagen forms the primary building blocks of skin, bones, tendons, ligaments, cartilage, and other connective tissues. Collagen provides strength, elasticity, and support to these tissues. It is essential for building healthy connective tissues. The fact that collagen makes up connective tissues is how and why we often call Hypermobility a ‘connective tissue disorder.” [11]

Collagen fibres have a tensile strength comparable to that of steel, meaning they can withstand a significant amount of stretching and pulling forces without breaking [12]. However, collagen is much more flexible and less dense than steel, making it ideal for human body tissues that need both strength and flexibility.

In the average human, connective tissues like collagen provide structural integrity to joints, tendons, and ligaments and many other supportive body structures that can brace or scaffold blood vessels, and organs.

Due to genetic changes affecting collagen creation or structure, my patients often notice “issues in their connective tissues”. They often say they “don’t feel well held together” as this is reflective that the connective tissues are not performing their job, stretching too much, causing joint issues like partial subluxations or full dislocations can lead to excessive joint laxity and instability, as well as body wide health issues and symptoms[13] [1].

These collagen issues can also affect your body’s ability to sense where your joints are in space, leading to chronic pain and fatigue for people with Hypermobility Spectrum Disorder[3]. In addition, alterations in collagen metabolism can impair proprioception and contribute to chronic pain and fatigue in individuals with Hypermobility Spectrum Disorders[8]. Connective tissues and especially collagen, provides structural support to various parts of the body, including the:

• Joints
• Skin
• Bones
• Nerves and neural systems
• Gut
• Bladder
• And many other organs.

When these tissues are more elastic than usual, it can lead to joint instability and other health issues. People with EDS have ineffective collagen, leading to less supportive connective tissues.

Diagnosis of hEDS

Diagnosing hEDS can be challenging due to the variability of symptoms and the lack of specific genetic markers. Diagnosis is typically based on clinical criteria, including a detailed medical history and physical examination. The 2017 international classification of Ehlers-Danlos syndromes provides guidelines for diagnosing hEDS.

Because there is no genetic test for hEDS, diagnosis relies on a combination of clinical signs and family history. The 2017 International Classification of Ehlers-Danlos Syndromes outlines specific criteria, including:

• Generalised Joint Hypermobility (measured using the Beighton Score)
• A history of joint instability-related injuries
• Other characteristic symptoms such as skin, dental, body wide and connective tissue abnormalities
• Chronic pain and relative with hEDS or EDS

Since many of the symptoms overlap with other conditions, a thorough medical evaluation is essential. If you suspect you have hEDS, a visit to a knowledgeable GP or rheumatologist is the best starting point. Additionally, you may wish to Take the test! to find out if you might benefit from professional support.

Management of hEDS

Once diagnosed, the focus shifts to managing hEDS with the goal of alleviating symptoms and improving quality of life. This often involves physical therapy (physiotherapy) to strengthen muscles and stabilise joints, pain management strategies, considering methods to manage fatigue, digestive and gut issues, and counselling and lifestyle modifications to reduce the risk of injury. Given the complexity of hEDS, multidisciplinary, holistic care, may be needed to support the individual, including several medical and allied health clinicians.

These elements should be collaboratively integrated to support overall wellbeing, addressing not just physical symptoms but also the broader impact on daily life and mental health.

A final note

Hypermobile Ehlers-Danlos Syndrome is a complex condition that requires a comprehensive approach to diagnosis and management. Understanding the symptoms and causes of hEDS is crucial for providing effective care and improving the quality of life for those affected by this condition. Living with hEDS can be challenging, but with proper management and support, individuals with the condition can lead fulfilling lives. It is important for patients to work closely with their healthcare providers to develop a personalised care plan that addresses their specific needs and symptoms.

If you suspect you have hEDS or have been recently diagnosed, connecting with specialists and support groups can be incredibly helpful.

For further reading, check out:

• Hypermobility Syndromes Association
• The Ehlers-Danlos Society
• Mayo Clinic on Ehlers-Danlos Syndrome
• You can find more information on the diagnostic criteria for these conditions here.

References

[1] Malfait, F., Francomano, C., Byers, P., et al. (2020). The 2017 international classification of the Ehlers-Danlos syndromes. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 175(1), 5-7.

[2] Gensemer, C., Burks, R., Kautz, S., Judge, D. P., Lavallee, M., & Norris, R. A. (2021). Hypermobile Ehlers‐Danlos syndromes: Complex phenotypes, challenging diagnoses, and poorly understood causes. Developmental dynamics, 250(3), 318-344. https://doi.org/10.1002/dvdy.220

[3] Castori, M., Tinkle, B., Levy, H., Grahame, R., Malfait, F., & Hakim, A. (2017). A framework for the classification of joint hypermobility and related conditions. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 175(1), 148-157.

[4] Blajwajs, L., Williams, J., Timmons, W. et al. Hypermobility prevalence, measurements, and outcomes in childhood, adolescence, and emerging adulthood: a systematic review. Rheumatol Int 43, 1423–1444 (2023). https://doi.org/10.1007/s00296-023-05338-x

[5] Demmler, J. C., Atkinson, M. D., Reinhold, E. J., Choy, E., Lyons, R. A., & Brophy, S. T. (2019). Diagnosed prevalence of Ehlers-Danlos syndrome and hypermobility spectrum disorder in Wales, UK: a national electronic cohort study and case–control comparison. BMJ open, 9(11), e031365-e031365. https://doi.org/10.1136/bmjopen-2019-031365

[6] Tinkle, B., Castori, M., Berglund, B., Cohen, H., Grahame, R., Kazkaz, H., & Levy, H. (2017). Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD): Clinical description and natural history. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 175(1), 48-69.

[7] Hypermobility Syndromes Association. (n.d.). What is hypermobility? Retrieved February 18, 2025, from https://www.hypermobility.org/what-is-hypermobility

[8] Tinkle, B., Castori, M., Berglund, B., Cohen, H., Grahame, R., Kazkaz, H., & Levy, H. (2017). Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD): Clinical description and natural history. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 175(1), 48-69.

[9] Nicholson, L. L., Chan, C., Tofts, L., & Pacey, V. (2022). Hypermobility syndromes in children and adolescents: Assessment, diagnosis and multidisciplinary management. Australian Journal of General Practice, 51(6).

[11] Grahame, R. (1999). Joint hypermobility and genetic collagen disorders: Are they related? Archives of Disease in Childhood, 80(2), 188. https://doi.org/10.1136/adc.80.2.188

[12] Yamamoto, N., & Nakamura, S. (2017). Relationships between the tensile strength and diameter of collagen fibrils isolated from mouse tail tendons. Journal of Biomechanical Science and Engineering, 12(3), 16-00511.

[13] Gensemer, C., Burks, R., Kautz, S., Judge, D. P., Lavallee, M., & Norris, R. A. (2021). Hypermobile Ehlers‐Danlos syndromes: Complex phenotypes, challenging diagnoses, and poorly understood causes. Developmental dynamics, 250(3), 318-344. https://doi.org/10.1002/dvdy.220