What is Hypermobile Ehlers-Danlos Syndrome (hEDS)?

Hypermobile Ehlers-Danlos syndrome (hEDS) is a connective tissue disorder that affects the body’s ability to produce strong and stable collagen—a protein essential for the integrity of skin, joints, blood vessels, and internal organs. hEDS is the most common form of Ehlers-Danlos syndromes (EDS), a group of 14 heritable conditions that share three hallmark features: generalized joint hypermobility, skin hyperextensibility, and tissue fragility.

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The Ehlers-Danlos Syndromes: A Family of Disorders
There are 14 recognized types of Ehlers-Danlos syndromes, each caused by a different genetic mutation that affects connective tissue. For 13 of these types, the specific gene mutations have been identified, allowing for molecular testing and clearer diagnostic criteria. However, hypermobile Ehlers-Danlos syndrome remains the only type without a known genetic cause. Despite intensive research, no definitive molecular marker has yet been identified for hEDS, making it a diagnosis based on clinical criteria rather than genetic testing.
 

This lack of a molecular signature complicates both diagnosis and research. Nonetheless, individuals with hEDS exhibit the core characteristics common to all EDS types—joint laxity, stretchy skin, and fragile tissues—but often present with a broader range of symptoms and varying degrees of severity.
 

A Brief History

The Ehlers-Danlos syndromes are named after two physicians—Edvard Ehlers, a Danish dermatologist, and Henri-Alexandre Danlos, a French physician—who each described patients with loose, hyperextensible skin and joint hypermobility in the early 1900s. Their observations laid the groundwork for recognizing a group of connective tissue disorders characterized by joint laxity, fragile skin, and poor wound healing.

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Throughout the 20th century, as clinical genetics advanced, researchers classified several subtypes of EDS based on distinct genetic and clinical features. However, one common and puzzling presentation—generalized joint hypermobility with pain, fatigue, and tissue fragility—lacked an identifiable genetic cause. This form was often diagnosed as Joint Hypermobility Syndrome (JHS), especially in the UK and parts of Europe, and as Ehlers-Danlos syndrome, hypermobile type in other settings, including the U.S. The two terms were often used interchangeably.

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In 2017, an international consortium of experts convened to clarify the classification system. The result was the current diagnostic framework that formally separated hEDS from JHS. Under this model

• hEDS was defined by stricter clinical criteria and continued to fall under the Ehlers-Danlos umbrella.

• Joint Hypermobility Syndrome and similar presentations that did not meet full hEDS criteria were reclassified as Hypermobility Spectrum Disorders (HSD)—a separate but related category.

This reclassification was intended to improve diagnostic clarity and ensure consistency across clinical and research settings. However, many experts believe that hEDS and HSD likely exist on a continuum, rather than being entirely distinct. Given their nearly identical symptoms and the absence of a genetic marker for either, it is widely anticipated that future discoveries—particularly a molecular cause—could lead to the reuniting of hEDS and HSD under a broader hEDS diagnosis.
 

How Common is hEDS?

While hEDS is the most prevalent subtype, its exact frequency in the population is difficult to determine. Population-based studies in Wales and the United States estimate the diagnosed prevalence of hEDS at approximately 1 in 3,100 people. However, experts believe this number is significantly underestimated. The condition is frequently underdiagnosed or misdiagnosed, partly due to its wide range of symptoms and the absence of a definitive diagnostic test.
 

Because of this, hEDS remains classified as a rare disease by the U.S. National Institutes of Health (NIH)—meaning it affects fewer than 200,000 people in the U.S.—but many clinicians and researchers suspect it is more common than currently recognized.
 

Who Gets hEDS?

hEDS affects people of all racial and ethnic backgrounds, but data on ethnic disparities in diagnosis remain limited due to underrepresentation in research and access to care. Current studies suggest that White individuals are more commonly diagnosed, but this may reflect diagnostic bias and healthcare access inequalities rather than true differences in prevalence.

There is a notable sex difference in diagnosis: females are diagnosed far more often than males—some studies suggest by a ratio of as much as 9:1. The reason for this imbalance is not fully understood. Biological sex differences in connective tissue, hormonal influences (such as estrogen affecting collagen), and gender-related differences in symptom reporting or healthcare utilization may all contribute.

The age at diagnosis varies significantly, but most individuals with hEDS report symptoms beginning in childhood or adolescence, particularly joint hypermobility, pain, and frequent sprains or injuries. However, a formal diagnosis is often delayed until adulthood, with many receiving a diagnosis in their 20s to 40s after years of unexplained symptoms. In some cases, diagnosis is made only after a triggering injury or a child’s diagnosis prompts evaluation of a parent.
 

Clinical Features 

Common symptoms include joint hypermobility, chronic pain, fatigue, easy bruising, and soft or stretchy skin. Many also experience autonomic dysfunction, gastrointestinal issues, and mental health symptoms. Symptom severity can fluctuate daily and often worsens with age or injury.

Diagnosis and Challenges 

Diagnosis is based on clinical criteria established in 2017, as no genetic test currently exists. This includes joint hypermobility, associated features, and exclusion of other conditions. Diagnostic delays are common due to symptom overlap with other disorders and variability in presentation.

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Management and Treatment

There is no cure for hEDS. Management focuses on symptom control and quality of life, typically through physical therapy, occupational therapy, pain management, and accommodations at school or work. Multidisciplinary care and individualized plans are key.
 

Research

Over the past decade, research on hEDS has expanded in both volume and scope. Earlier studies focused mainly on joint laxity and musculoskeletal symptoms, but recent research has adopted a biopsychosocial lens, examining the disorder’s impact on work, education, and mental health. Chronic pain, fatigue, and comorbid anxiety and depression are now recognized as major contributors to disability.
 

Longitudinal studies show that symptom severity may worsen with age or cumulative injury, though some individuals report adaptation and improved coping. Recommended accommodations include ergonomic tools, flexible schedules, assistive devices, and extended testing time—though evidence for some remains theoretical. Recent studies emphasize the importance of self-management strategies and comprehensive care.
 

Despite growth, research remains limited by the lack of biomarkers, diagnostic inconsistency, and underrepresentation of marginalized populations. Nevertheless, new studies are exploring immune dysfunction, autonomic dysregulation, neurodivergence, and patient experiences, and scoping reviews are increasingly common.
 

Visibility and Awareness

Public awareness of hEDS has grown dramatically over the past 10–15 years. Before 2010, hEDS was virtually unknown outside of specialist clinics. Patients were often misdiagnosed with anxiety or dismissed entirely. The 2017 diagnostic reform spurred greater visibility, aided by online communities, advocacy, and social media platforms like TikTok and Instagram.

While this increased visibility has empowered patients and brought attention to medical gaslighting and delayed diagnosis, misinformation remains a concern. Oversimplified portrayals can trivialize the condition, and public understanding still lags behind awareness.

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The Role of the NIH

The National Institutes of Health (NIH) is the key U.S. agency for biomedical research, distributing roughly $49 billion in funding in fiscal year 2023. However, hEDS itself doesn’t receive a dedicated, disease-specific line item. Studies relevant to hEDS are typically funded within broader connective tissue or musculoskeletal disorders by institutes like NIAMS or NCATS.

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In context, major diseases such as multiple sclerosis or lupus may receive hundreds of millions to over a billion dollars annually, while hEDS research, when isolated, receives only small portions—often a few million at most, and sometimes primarily through private foundations. This means that hEDS is significantly underfunded relative to its burden, relying heavily on specialized private grants (e.g., from The Ehlers‑Danlos Society or Segal Foundation) and investigator-initiated NIH grants spanning broader categories.

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The Role of The Ehlers-Danlos Society

Founded in 1985 and relaunched in 2016, The Ehlers-Danlos Society is a global nonprofit organization dedicated to advancing research, awareness, education, and patient support for all types of Ehlers-Danlos syndromes and hypermobility spectrum disorders. The Society provides a wide range of resources for individuals living with hEDS and related conditions, including international conferences, physician directories, patient support groups, and updates on scientific advances. It also funds research efforts aimed at identifying the genetic basis of hEDS and improving diagnostic accuracy and treatment. Through its advocacy and educational work, The Ehlers-Danlos Society plays a central role in uniting the global community affected by these complex and often misunderstood disorders.
 

Looking Ahead

As research into hEDS continues, hopes are high that the genetic basis will be discovered, allowing for better diagnosis and targeted treatments. Meanwhile, the increasing attention to patient experience, mental health, and function reflects a maturing field. Improved recognition, clinical care, and advocacy promise a more informed and compassionate future for individuals living with hEDS.
 

Summary

Hypermobile Ehlers-Danlos syndrome is a complex, under-recognized connective tissue disorder marked by joint hypermobility, tissue fragility, and a wide array of symptoms. While it shares its core features with other EDS types, its unknown genetic cause and broad variability make it uniquely challenging. hEDS disproportionately affects women, symptoms often begin in childhood, and the syndrome most likely remains underdiagnosed in many populations. The classification has evolved over time, but the condition itself remains poorly understood. Organizations like The Ehlers-Danlos Society and the National Institutes of Health are helping to drive research, improve care, and bring hope to those living with this difficult but increasingly recognized disorder.

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