Understanding the Invisible Illnesses of Hypermobility

Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorder (HSD) are often associated with flexible or “double-jointed” joints. However, both are increasingly recognised as complex, multisystem connective tissue disorders that can affect far more than simply your muscles and joints [1, 2, 3].

Having a diagnosis of HSD can be just as life-impacting and debilitating as hEDS. People with symptomatic hypermobility, hEDS and HSD often experience multiple comorbidities or co-occurring health conditions. These symptoms and conditions can present as: significant pain across the muscles, joints and other body parts; automatic body function impact (fatigue, heart racing, temperature regulation, dizziness, etc), anxiety, gut and digestion issues, conditions usually relating to the nervous or immune systems, neurodivergence and mental health problems. These co-occurring conditions/symptoms are often known as additional “Invisible Illnesses”, and for many, these conditions have a greater impact on daily life than joint instability and pain alone [4, 5, 6, 7,8].

This article explores why these conditions commonly occur together, helping move the discussion beyond “bendy joints” and towards a more accurate understanding of hEDS and HSD as interconnected, whole-body conditions.

Health conditions, comorbidities and co-occurring conditions: What’s the difference?

• A health condition is any disease, disorder, injury, syndrome, or ongoing physical or mental health issue that affects a person’s health, wellbeing, or daily functioning.
• A comorbidity is an additional health condition or health issue that exists alongside a primary diagnosis. The term “comorbidity” does not mean automatically that one condition caused another. It simply means that two or more conditions are present in the same person.

While the term “comorbidity” has traditionally been used in medicine, many clinicians and researchers discussing hEDS and HSD now prefer “co-occurring conditions.” This term better reflects how complex and interconnected these presentations can be.

It also avoids suggesting that one condition is secondary, less important, or separate from the wider clinical picture. For example, treating joint instability, chronic pain, gastrointestinal dysfunction, autonomic symptoms, fatigue, and migraine as unrelated problems may mean the broader pattern is missed.

The distinction is therefore important. A comorbidity may be recorded as an additional diagnosis, while “co-occurring condition” recognises that several conditions may be present and interact, even when their exact relationship is not yet fully understood.

Why so many “Invisible Illnesses” occur together in hEDS/HSD – New research

Connective tissue was originally thought to be the main reason hEDS and HSD affect so many parts of the body. It gives the body strength, flexibility, support and cushioning. Connective tissue is found not only in joints and ligaments, but also in and around muscles, fascia, tendons, skin, blood vessels, nerves, the digestive system and organs such as the heart, lungs and bladder. Because it is found throughout the body, changes in connective tissue and the surrounding support network may contribute to symptoms in several body systems [2, 11, 12, 13].

Current research suggests that hEDS and HSD are probably caused by several interacting factors, rather than one problem with collagen or connective tissues. Changes in the body’s support network, fascia, cell communication, muscle control, automatic body functions, immune activity, pain processing and nerve function may all play a part [4, 11, 12, 13, 14, 15, 16].

This helps explain why a person with hEDS or HSD may experience different combinations and severity of joint instability, pain, fatigue, dizziness, poor sleep, digestive symptoms, body awareness, anxiety, autonomic function and difficulty with daily activities, rather than only joint hypermobility.

The precise causes and relationships between these mechanisms are still being investigated.

The most common co-occurring conditions / “Invisible Illnesses” in the Symptomatic Hypermobility Syndromes and hEDS

Chronic widespread pain

Chronic pain is one of the most common and disabling features of hEDS and HSD. It may result from joint instability, muscle overuse, nerve irritation, or central pain sensitisation, where the nervous system becomes more sensitive and pain persists or spreads beyond the original injury [17, 18, 19]. Pain often fluctuates and may not be clearly explained by imaging, which can delay diagnosis.

Joint instability, subluxations and dislocations

Subluxations and dislocations are common in both hEDS and HSD. A subluxation is a partial dislocation, while a full dislocation occurs when the joint surfaces lose contact and move out of alignment. This ongoing joint instability can also cause muscle guarding, nerve irritation, fear of movement, and ongoing pain [5, 20, 21].

Postural Orthostatic Tachycardia Syndrome (POTS) and dysautonomia

Autonomic dysfunction is common in hEDS and HSD. POTS is only one presentation in dysautonomia or autonomic dysfunction and can cause dizziness, palpitations, fatigue, brain fog, nausea, and fainting when standing. Lax connective tissue in blood vessels may contribute to blood pooling and poor circulation, triggering these symptoms [22, 23, 24].

Fatigue and Chronic Fatigue Syndrome (CFS)

Fatigue in hEDS and HSD is often persistent and can be severe or out of proportion to activity. It may be linked to pain, poor sleep, autonomic dysfunction, immune activation, gut issues, sensory system overload and the extra effort needed to stabilise hypermobile joints [19, 24].

Gastrointestinal disorders

Common digestive symptoms include reflux, bloating, constipation, diarrhoea, nausea, early fullness, and abdominal pain. Irritable bowel syndrome, gut dysmotility, and functional gastrointestinal disorders are also frequently reported [25]. Connective tissue differences-hypermobility within the gut and autonomic dysfunction have been found to affect gut movement, sensitivity, and digestion [14, 25, 26, 27].

Headache and migraine disorders

Migraine and chronic headache are much more common in people with hEDS and HSD than in the general population. Possible contributors include cervical instability, muscle tension, autonomic dysfunction, and altered pain processing [28, 29, 30].

Anxiety disorders

Anxiety is more common in hEDS and HSD, but this does not mean physical symptoms are psychological. Possible shared mechanisms include autonomic nervous system and actual nervous system differences and increased interoceptive awareness, or sensitivity to internal body signals [31, 32, 33]. Anxiety may also result from unpredictable symptoms, functional limitations, ongoing invalidation and long diagnostic delays.

Depression

Depression is reported more often in people with hEDS and HSD, particularly when pain, fatigue, and functional limitations are poorly managed. Social isolation, medical invalidation, and repeated treatment failures can also affect mental health [34].

Sleep disorders

Common sleep problems include insomnia, non-restorative sleep, restless legs, and sleep-disordered breathing. Pain, autonomic symptoms, and anxiety can disrupt sleep, while poor sleep can worsen fatigue and pain sensitivity [6] .

Neurodivergent conditions, including ADHD and autism

Higher rates of ADHD and autism have been reported in people with hEDS and HSD. Research is ongoing, including into possible shared neurodevelopmental and connective tissue pathways [9, 31, 32, 35, 36].

Mast cell activation disorders

Mast cell activation symptoms, including flushing, itching, hives, gastrointestinal upset, bloating, headaches, and medication sensitivities, are frequently reported in hEDS and HSD. Research is still developing, but mast cell activation and immune dysregulation appear to overlap with connective tissue disorders in some people [37, 38, 39].

Temporomandibular joint disorders

TMJ disorders can cause jaw pain, clicking, locking, headaches, and facial pain. They may result from jaw hypermobility and muscle overuse and can affect eating, speaking, and quality of life [9].

Pelvic floor dysfunction and gynaecological conditions

Pelvic floor dysfunction can affect people of all genders and may cause bladder or bowel problems, prolapse, pelvic pain, and sexual pain. Reduced connective tissue support, pain, and muscle guarding may all contribute [4, 6, 40].

Small fibre neuropathy

Small fibre neuropathy affects nerves involved in pain and autonomic function. Symptoms can include burning pain, tingling, temperature sensitivity, altered sweating, and other autonomic problems. Research suggests it may be under-recognised in hEDS and HSD [4].

Cardiovascular differences

Most people with hEDS or HSD do not have life-threatening heart conditions. However, mild valve changes, orthostatic intolerance, and circulation problems are more common and may worsen fatigue, exercise intolerance, and autonomic symptoms [6].

Why this matters for diagnosis and care

Because hEDS and HSD can affect many body systems, people often see multiple health professionals before receiving an accurate diagnosis. Their symptoms may be treated separately, without anyone recognising the broader pattern.

Some people are told that their symptoms are unrelated, caused by stress, or “just anxiety.” This can contribute to delayed diagnosis, repeated investigations, medical traumatisation invalidation, and treatments that do not address the full clinical picture [41, 42].

Recognising common co-occurring conditions can help to:

• Validate people’s experiences
• Reduce diagnostic delays and improve treatment planning
• Encourage multidisciplinary care
• Identify patterns across different body systems
• Shift the focus from isolated symptoms to whole-person management

For people living with hEDS and HSD

hEDS and HSD are not simply conditions of flexible or unstable joints. They are complex, interconnected conditions that can affect the body as a whole. Recognising common co-occurring conditions can help people better understand their symptoms and feel less alone. It may also help explain why concerns such as pain, fatigue, digestive problems, dizziness, migraine, sleep difficulties, and other symptoms can occur together.

HSD can be just as disruptive as hEDS, even when a person does not meet the full diagnostic criteria for hEDS. Every presentation is different, but symptoms should not be dismissed simply because they affect several body systems or cannot be explained by one diagnosis.

Understanding the wider pattern is an important step towards more coordinated, compassionate, and effective care.

For GPs and Allied Health Professionals

Hypermobile Ehlers-Danlos syndrome and Hypermobility Spectrum Disorders are multisystem connective tissue disorders, not isolated musculoskeletal conditions. Many patients experience significant multimorbidity involving the autonomic, gastrointestinal, neurological, immune, psychological, and musculoskeletal systems.

Why this matters in clinical practice

Patients may present with fragmented symptoms and consult several health professionals before the wider pattern is recognised. Diagnostic delays are common, and physical symptoms may be incorrectly attributed to anxiety or functional illness.

Clinicians should consider hEDS or HSD when a patient presents with:

• Long-standing pain alongside hypermobility
• Joint instability or recurrent subluxations
• Multiple unexplained symptoms across different body systems
• Poor responses to standard single-system treatments
• Symptoms beginning in childhood or adolescence
• A family history of hypermobility or related conditions

Common co-occurring concerns that may require screening include:

• Chronic widespread pain
• Joint instability and poor injury recovery
• Persistent fatigue and non-restorative sleep
• Migraine and chronic headache
• Anxiety and depression, which may be co-occurring not the main cause
• Dysautonomia or POTS
• Central sensitisation of pain, fibromyalgia or FND
• Gastrointestinal disorders
• Mast cell activation symptoms
• Pelvic floor dysfunction
• Temporomandibular joint disorders
• Neurodivergent traits, including ADHD and Autism
• Small fibre neuropathy

Principles of care

Management should reflect the multisystem nature of hEDS and HSD. Depending on the patient’s needs, this may involve support from general practitioners, physiotherapists, occupational therapists, psychologists, cardiologists, gastroenterologists, and other relevant health professionals [43, 44, 45].

Important principles include:

• Validating the patient’s symptoms and provide hope (treatment and management options are available)
• Recognising multisystem involvement as part of the clinical picture
• Screening proactively rather than reactively
• Looking for patterns and clusters of symptoms
• Focusing on function, pacing, and quality of life
• Coordinating care across health disciplines where needed

Symptomatic Hypermobility, hEDS and HSD are conditions of complexity, not hypochondria or exaggeration. Treating each symptom as an unrelated problem can lead to missed diagnoses, delayed care, and poorer outcomes.

Recognising predictable patterns of co-occurring conditions can improve diagnostic confidence, strengthen patient trust, and support safer and more effective management.

A whole-body condition requires whole-person care.

Are you a health professional looking to learn more?

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