Introduction

Overview of ehlers-danlos syndrome (EDS)

Ehlers-Danlos Syndrome (EDS) is an umbrella term used for 13 different types of inherited (genetic) medical conditions that affect connective tissue within the body.¹ EDS is commonly inherited through a process called autosomal dominant inheritance, where a child only needs to inherit one faulty gene from one of their parents to develop EDS.1 However, sometimes the gene is not inherited, and EDS occurs for the first time in the family’s medical history.¹

EDS affects the body’s ability to produce collagen, which is a protein found in the body that is the primary building block of the skin, muscles, bones, ligaments, and connective tissue.^2,3

Some of the types of EDS are:¹

• Hypermobile EDS (known as hEDS) - Most common, causes mobility, gastrointestinal, skin issues, chronic pain and more¹ 
• Classical EDS - Tends to have a more prominent effect on the skin and its surface
• Vascular EDS - The most serious type of EDS affecting blood vessels and internal organs¹

Hypermobile EDS has an incidence rate of approximately 1 in 10,000; however, it can be difficult to diagnose due to the variability of symptoms and complexity of the disease.² Therefore, it is likely that this is an underestimation of the incidence of hypermobile EDS.²

Autonomic dysfunction

Autonomic dysfunction (also known as dysautonomia) is a group of medical disorders that affect the autonomic nervous system (ANS).⁴ The ANS is a component of the peripheral nervous system (PNS) and is responsible for regulating involuntary (automatic) processes in the body to maintain homeostasis.⁵ These involuntary processes include:⁵

• Heart rate
• Blood pressure
• Breathing
• Digestive processes
• Body temperature⁴
• Bladder control⁴

Symptoms of EDS 

Typical symptoms of EDS include:¹

• Joint hypermobility 
• Unstable joints - have the potential to dislocate easily
• Joint pain
• Fatigue
• Dizziness
• Chronic pain²
• Increased heart rate when standing up
• Digestive problems, e.g. heartburn and constipation
• Skin that bruises easily
• Problems with bladder control, such as urinary incontinence 
• Muscle weakness - some patients report difficulty walking²
• Delayed wound healing
• Thin scars left on the skin after wound healing²
• Diahorrea²
• Changes to internal organs - can result in spontaneous rupture²

EDS and dysautonomia 

Ehlers-Danlos Syndrome, particularly hEDS, is frequently associated with autonomic dysfunction, a condition where the ANS  does not function properly.⁴ The link between EDS and dysautonomia is thought to be due to connective tissue abnormalities as a result of damage to collagen. This affects blood vessels, leading to blood pooling and a reduced ability to regulate blood pressure and heart rate, thus affecting the ANS.⁶ The most common form of dysautonomia linked to EDS is Postural Orthostatic Tachycardia Syndrome (PoTS), a form of orthostatic intolerance that causes symptoms when standing up or in an upright position.⁴

Postural orthostatic tachycardia syndrome - PoTS

PoTs causes an exaggerated increase in heart rate upon standing, typically a rise in heart rate of >30 bpm (beats per minute) in adults and >40bpm in teenagers. There is typically no fall in blood pressure.⁶ PoTS affects approximately 0.2% of the UK’s population, and is more prevalent in females aged between 15 and 50 than in males.⁷ It is typically diagnosed in adolescence, causing significant disability that can interfere with social activities, work, sports and school.⁹ Similar to EDS in general, PoTS is typically underdiagnosed because its symptoms are closely related to conditions such as chronic fatigue syndrome (CFS).⁷ Symptoms of PoTS include:^7,8

General symptoms

• Temperature sensitivity
• Shaking
• Sleep disturbances
• Exercise intolerance
• Sweating 
• Weakness/heaviness of the legs¹⁰

Cardiovascular and respiratory symptoms

• Dizziness
• Chest pain
• Shortness of breath
• Heart palpitations (being aware of your heart beating fast)
• Fainting (or feeling faint)

Neurological symptoms

• Brain fog (cognitive difficulties)
• Headaches
• Anxiety

Gastrointestinal and urinary symptoms

• Nausea
• Gut issues
• Bladder issues

In a recent 2024 study looking at the long-term effects of the condition, female patients with PoTS demonstrated a greater symptom severity and duration than males, with 99% of female patients reporting ongoing symptoms. The researchers concluded that PoTS appears to be worse in female patients – a suggestion confirmed by a previous study that reported a female-to-male ratio of 5:1.^9,10

Link between EDS and PoTS

In a study by Gazit et al. 2003, 80% of EDS patients demonstrated symptoms associated with PoTS, which suggests high comorbidity.^11,12,13 Roma et al. 2018 estimated 41-49% of individuals with EDS also had PoTS.¹⁴ The precise prevalence of individuals with EDS also having PoTS varies between studies, despite there being a well-established clinical link between hEDS and PoTS.¹⁵ The exact pathophysiology that links EDS and PoTS is also unknown;¹⁵ however, there are two prominent theories regarding the connection.

Connective tissue laxity theory

Connective tissue laxity theory suggests that loose connective tissues present in individuals with hEDS make blood vessels more stretchy, leading to the vessels being unable to constrict properly when the individual stands up.^15,16 Due to this, blood pools in the body, leading to PoTS symptoms.^15,16  Although direct scientific evidence is lacking, this is the most hypothesised and widely accepted theory about the connection between EDS and PoTS.¹⁴

Small fibre neuropathy theory

Individuals with EDS tend to show a higher rate of damage to small nerve fibres, known as small fibre neuropathy.^15,17 These fibres are vital in the ANS to control automatic bodily functions such as blood pressure and heart rate; therefore, damaged small nerve fibres may contribute to PoTS in individuals with EDS.^15,17

Diagnostic approaches

EDS diagnosis

There are currently no clinical tests for EDS diagnosis.¹ The diagnosis is based on a combination of a physical examination and assessing previous family medical history.¹

Genetic testing is available for other subtypes of EDS except hEDS (commonly associated with PoTS), as the genetic basis of this subtype is currently unknown.¹⁸ Hypermobile EDS is typically diagnosed by the Beighton score assessment, which measures joint hypermobility using a range of movements, on a 9-point scale.¹⁹ A positive Beighton score is 5/9 points in adults, 6/9 points in children (pre-puberty) and 4/9 points in adults over the age of 50 years old.¹⁹ The joints assessed are:¹⁹

• Elbows
• Knees
• Base of thumbs
• Knuckles of pinky fingers
• Spine 

PoTS diagnosis

There are two main tests for PoTS diagnosis: the active stand test and the tilt-table test.⁷ The active stand test is a short test that assesses and monitors an individual's heart rate and blood pressure, to determine how the cardiovascular system responds to a change in posture, particularly from sitting down to standing up.⁷ During the tilt-table test, the individual lies flat on a table that is then tilted to a standing position, while monitoring the individual's heart rate and blood pressure.²⁰ A significant increase in heart rate, without a decrease in blood pressure, strongly suggests a PoTS diagnosis.²⁰

Management and treatment approaches

As there is currently no cure for EDS and PoTS, the treatment options for individuals diagnosed with both conditions should focus on managing symptoms and preventing disease progression and complications.² Treatment needs to be individualised to the patient, depending on the clinical symptoms.⁴ Psychological support for both conditions is also required to manage these chronic illnesses and provide additional support to individuals and families, such as cognitive behaviour therapy (CBT).¹

EDS 

The NHS states that people diagnosed with EDS often require multiple healthcare providers in different specialities to manage the condition, which are:¹

• A physiotherapist - to learn exercises to strengthen joints, manage pain, and avoid injuries
• An occupational therapist helps with daily activities

PoTS

For managing PoTS, the NHS recommends making lifestyle adjustments, which could include:⁸

• Increased fluid and salt intake (at least 6 grams a day) - helps to increase blood volume⁴
• Eating small meals, low in refined carbohydrates
• Limiting caffeine and alcohol intake²¹
• Avoid standing for long periods of time²¹
• Wearing compression clothing, e.g. knee-high socks
• Gradual movement - avoiding sudden changes in posture

According to PoTS.In the UK, there are no specific medications tailored to PoTS; however, medications such as beta-blockers and ivabradine can be prescribed to slow down the heart rate.²² Healthcare providers may tailor the type of medication prescribed, depending on the symptoms the individual is experiencing and potential co-existing medical conditions such as EDS.²² 

Summary 

Ehlers-Danlos Syndrome (EDS) is an umbrella term for a group of 13 inherited conditions that can cause a range of symptoms, including joint hypermobility, pain and fatigue. The most common type of EDS is hypermobile EDS (hEDS), which is commonly associated with autonomic dysfunction (also known as dysautonomia), where the autonomic nervous system (ANS), responsible for controlling involuntary processes, e.g. heart rate, does not function properly.

Postural Orthostatic Tachycardia Syndrome (PoTS) is a type of dysautonomia that causes symptoms such as heart palpitations, brain fog and fainting. PoTS has been closely linked to hEDS, although the pathophysiology of the co-morbidities is not known, despite there being two possible theories: connective tissue laxity theory and small fibre neuropathy theory. 

Diagnostic approaches for the conditions include the Beighton score test for EDS and the active stand and tilt-table test for PoTS. Management and treatment approaches involve lifestyle adjustments and multidisciplinary care to manage symptoms and prevent disease progression. Individuals experiencing symptoms of EDS or PoTS should contact their healthcare provider.