Controversies & Issues

Controversies and Challenges in hEDS

Although growing recognition suggests that hypermobile Ehlers-Danlos syndrome (hEDS) is more prevalent than once believed, it remains one of the most controversial and poorly understood medical conditions, despite its significant impact on patients’ lives. Its lack of a molecular marker, evolving diagnostic criteria, diverse symptom presentation, and unequal access to diagnosis and care all contribute to confusion and inconsistency in how the condition is recognized and managed. This article explores the major controversies surrounding hEDS, including diagnostic uncertainty, challenges in symptom recognition, barriers to care, and social disparities.

Diagnostic Criteria and Ongoing Debate

The diagnostic framework for hEDS has been a source of ongoing debate. In 2017, an International Consortium established new criteria to improve diagnostic precision. These criteria require three main elements: (1) generalized joint hypermobility (GJH), (2) musculoskeletal and systemic features that suggest a connective tissue disorder, and (3) the exclusion of other heritable or acquired conditions through clinical evaluation and, when possible, genetic testing.

Unlike most other subtypes of Ehlers-Danlos syndrome, hEDS lacks a known genetic mutation. As a result, diagnosis is entirely clinical, based on physical signs, symptoms, and exclusion of other conditions. This stands in contrast to many other forms of EDS, where molecular testing can confirm a diagnosis. The transition from the older 1997 Villefranche criteria to the 2017 guidelines narrowed the diagnostic pool and excluded many individuals who had previously been diagnosed. While this change was intended to improve consistency and aid research, it also led to diagnostic uncertainty and the perception of being "undiagnosed" for many symptomatic individuals.

The distinction between hEDS and hypermobility spectrum disorders (HSD)—which are diagnosed when a person has features of joint hypermobility but does not meet full hEDS criteria—remains murky. Clinically, patients with HSD and hEDS often experience the same symptoms and require similar care, yet they may receive different diagnoses or face different treatment pathways.

Diagnostic Challenges

Diagnosing hEDS is further complicated by the limitations of current assessment tools. The Beighton score, commonly used to assess joint hypermobility, can yield inconsistent results depending on the examiner. Some features of hypermobility are also age-dependent: young children may appear more flexible than they are due to developmental norms, while older adults may have reduced mobility due to aging or joint damage, making it harder to meet the criteria.

Another challenge is the requirement to exclude other connective tissue disorders. This typically involves genetic testing, which is expensive, not always available, and may not be covered by insurance. Although there are pediatric-specific diagnostic frameworks that account for age-related factors and developmental changes, these are not consistently implemented in clinical practice.

Is hEDS Just a Connective Tissue Disorder?

hEDS is traditionally classified as a heritable connective tissue disorder because its most visible and consistent signs—joint instability, stretchy skin, and tissue fragility—are rooted in the structure and function of connective tissue. Connective tissue forms the scaffolding of the body, supporting joints, skin, blood vessels, organs, and nerves. hEDS is believed to involve defects in collagen or the extracellular matrix (ECM), the structural framework that holds tissues together.

However, many symptoms of hEDS extend beyond what can be explained by connective tissue weakness alone. Individuals with hEDS frequently experience dysfunction in multiple body systems, such as

The autonomic nervous system, often presenting as postural orthostatic tachycardia syndrome (POTS), which causes dizziness, rapid heart rate, and fatigue.
The immune system, with many patients reporting symptoms suggestive of mast cell activation, such as hives, flushing, or food sensitivities.
The digestive system, where conditions like irritable bowel syndrome (IBS) and gastroparesis are commonly reported.
Neurodevelopmental conditions, including a higher incidence of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).

These systemic symptoms—such as chronic fatigue, brain fog, and lightheadedness—suggest dysregulation at the level of the nervous or immune systems, rather than being explained solely by connective tissue fragility.

In response to these complexities, some researchers have proposed reclassifying hEDS using broader terms. Emerging frameworks suggest viewing it as a multisystem dysregulation disorder, a neuroconnective phenotype, or part of a broader Connective Tissue Spectrum Disorder (CTSD). These models acknowledge the widespread effects of hEDS and may provide a more accurate foundation for diagnosis, treatment, and research.

While hEDS remains officially classified as a connective tissue disorder, this label likely oversimplifies the condition. A more comprehensive model that accounts for multisystem involvement may better serve patients and researchers alike.

Symptom Variability and Impact

hEDS presents a highly variable symptom profile that affects multiple organ systems. People living with hEDS may experience chronic pain, fatigue, joint dislocations or instability, autonomic nervous system dysfunction (such as POTS), gastrointestinal problems, and mental health challenges including anxiety, depression, or ADHD.

This wide-ranging symptom burden can significantly impair quality of life. Many individuals struggle with daily functioning, social participation, and employment, often experiencing isolation, physical limitations, and emotional distress. Unfortunately, the lack of awareness about the systemic nature of hEDS often results in underdiagnosis, invalidation, and fragmented care.

Treatment Limitations and Evidence Gaps

There are currently no treatments that alter the course of hEDS or address its root cause. As a result, management focuses on symptom control and supportive care. Most treatment plans are multidisciplinary, involving physical therapy, pain management strategies, and behavioral interventions to improve functioning and quality of life.

However, evidence to support best practices is limited. Much of the available guidance comes from small observational studies or clinical consensus rather than large-scale trials. Compounding these challenges, many physicians receive little or no formal education on hEDS, leading to uncertainty in treatment approaches and under-referral to supportive services. Another major obstacle is that hEDS is a multisystemic condition, and no single medical specialty has taken ownership of it. As a result, patients are often referred from one specialist to another without any provider assuming comprehensive responsibility for care.

Access to treatment is also a significant barrier. Patients often encounter long waitlists, geographic limitations, or financial constraints when trying to obtain physical therapy, occupational therapy, or psychological services.

Access to Care and Systemic Barriers

Many individuals with hEDS face significant challenges in the healthcare system. A primary issue is the widespread lack of provider knowledge, which can delay diagnosis or lead to mismanagement. Even when diagnosed, patients may struggle to find specialists familiar with hEDS or willing to coordinate care across multiple disciplines.

Insurance restrictions and high out-of-pocket costs further limit access to essential treatments. These issues are especially pronounced in rural and underserved areas, where few providers have experience with complex, multisystem conditions like hEDS. As a result, patients often go without the care they need or must travel long distances to receive appropriate services.

Social Determinants and Disparities

Health outcomes for people with hEDS are not distributed evenly. Socioeconomic status, race, ethnicity, and geographic location can all influence the likelihood of receiving a timely and accurate diagnosis. People of color and low-income patients are underrepresented in research and are more likely to experience diagnostic delays or inadequate care.

In some cases, provider bias or systemic racism exacerbates these disparities, creating additional barriers to treatment and recognition. These inequities highlight the need for more inclusive research, provider education, and policy reforms to ensure equitable care across diverse populations.

Pediatric and Transition Issues

Diagnosing hEDS in children poses unique challenges. Young children may appear unusually flexible due to age-appropriate joint laxity, making it difficult to distinguish between normal development and pathological hypermobility. Moreover, many symptoms of hEDS, such as fatigue or gastrointestinal issues, may not become apparent until later childhood or adolescence.

The transition from pediatric to adult care is another vulnerable period. Many adolescents with hEDS lose access to supportive pediatric services without a clear pathway to adult providers who understand their condition. This gap can lead to delayed care, increased symptom burden, and a decline in functioning during a critical developmental stage.

Research Gaps and Promising Initiatives

Scientific understanding of hEDS remains limited, in part due to the lack of a known genetic marker. However, research is ongoing. The HEDGE project (Hypermobile Ehlers-Danlos Genetic Evaluation) is a global initiative aiming to identify the molecular basis of hEDS through large-scale genetic analysis.

In addition to genetic work, researchers are exploring plasma-based biomarkers—such as the breakdown products of extracellular matrix proteins—as potential diagnostic tools. While these findings are promising, they are not yet validated for clinical use.

Efforts are also underway to develop standardized outcome measures and clinical guidelines. These tools are critical for improving consistency in care and enabling future research trials that can evaluate the effectiveness of various treatments.

Patient Advocacy and Public Awareness

Growing public awareness of hEDS has helped some patients get diagnosed sooner and access more information. However, increased awareness also carries the risk of overdiagnosis, especially when the criteria used are broad or interpreted subjectively. Social media, online support groups, and personal narratives may shape public understanding in ways that don’t always reflect clinical evidence.

Self-diagnosis and confirmation bias can skew prevalence estimates and make it more difficult to conduct accurate epidemiological research. Nonetheless, patient-led advocacy continues to play a key role in pushing for better care, funding, and visibility.

Coding Practices and Epidemiological Inconsistencies

Accurate tracking of hEDS is hampered by inconsistent diagnostic coding. Variations in the use of ICD (International Classification of Diseases) codes between countries and even among providers make it difficult to determine how many people are affected and how care is being delivered. As a result, prevalence estimates vary widely depending on region, study design, and diagnostic criteria used. Improved coding practices are necessary to advance research and allocate healthcare resources effectively.

Summary

Hypermobile Ehlers-Danlos syndrome is a complex, multisystem disorder with no clear biomarker, inconsistent diagnostic practices, and major barriers to care. These challenges are compounded by social disparities, limited research funding, and a healthcare system ill-equipped to manage chronic, poorly understood conditions. Nevertheless, progress is being made. Ongoing research initiatives, growing patient advocacy, and efforts to improve provider education hold promise for a future in which individuals with hEDS can access timely, equitable, and evidence-based care.