Ehlers-Danlos Syndrome: Symptoms, Types, Causes and Treatment

Ehlers-Danlos Syndrome (EDS) is a group of rare, inherited connective tissue disorders known for their striking diversity in symptoms and severity. People living with EDS often face a range of challenges, from persistent joint pain to life-threatening vascular complications. Understanding EDS requires an exploration of its many faces: its symptoms, the different types, underlying causes, and available treatments. This comprehensive article brings together the latest research to provide a clear, engaging guide for patients, families, and clinicians navigating the complex world of EDS.

Symptoms of Ehlers-Danlos Syndrome

Living with EDS is often described as a journey through a landscape of unpredictable symptoms. From the outside, some signs may be subtle, but for those affected, the impact is profound—ranging from daily discomfort to severe health emergencies. Knowing the core symptoms is the first step toward timely diagnosis and better management.

Symptom	Description	Prevalence/Impact	Source(s)
Joint Hypermobility	Unusually flexible joints, frequent subluxations/dislocations	Very common; may cause pain & instability	1 2 5 7 10
Skin Hyperextensibility	Skin stretches more than usual, feels soft	Common; varies by type	1 5 7 9
Chronic Pain	Persistent, sometimes severe musculoskeletal pain	Highly prevalent; debilitating	1 2 3 17
Easy Bruising	Skin bruises easily, sometimes without clear cause	Seen in all subtypes	4 5 6
Fatigue	Tiredness not improved by rest	Common and disabling	1 2 3
Vascular Fragility	Fragile blood vessels, risk of rupture	Especially in vascular type	4 6 8 15
Other Symptoms	Headaches, gastrointestinal issues, poor wound healing	Variable by subtype	2 5 3 17

Table 1: Key Symptoms

Core Musculoskeletal Manifestations

The hallmark of EDS is joint hypermobility, where joints move beyond the normal range. This flexibility often leads to instability, frequent joint subluxations, and dislocations. Many patients report their first symptoms as children or teenagers, with musculoskeletal pain starting early and often becoming chronic and widespread 1 2 5 10.

Chronic pain is not just physical; it affects daily life, limiting mobility, work, and social participation. It's more commonly reported and severe in the hypermobile type of EDS but can affect all subtypes 1 2 3 17. Muscle weakness, myalgia, and easy fatigability compound these difficulties, contributing to reduced quality of life 2 3.

Skin and Soft Tissue Features

Skin abnormalities are another signature of EDS. Skin may be unusually soft, velvety, and hyperextensible—it stretches more than expected and snaps back. Easy bruising is nearly universal, and in some forms, wounds heal poorly, often leaving thin, atrophic scars 4 5 7 9. Some individuals also experience slow or abnormal wound healing and increased risk of hernias.

Vascular and Neurological Symptoms

Some types of EDS, most notably the vascular subtype, cause extreme fragility of blood vessels and hollow organs. This can lead to life-threatening complications, such as arterial or bowel rupture, often with few warning signs 4 6 8 15. Neurological symptoms, including headaches (particularly migraine), muscle weakness, reduced vibration sense, and even motor delay, are increasingly recognized 2 3. Fatigue and sleep disturbances are common and can be as disabling as physical symptoms 1 2 3.

Additional Manifestations

• Gastrointestinal problems (e.g., abdominal pain, constipation, or diarrhea)
• Gum bleeding, dental fragility
• Poor wound healing and atrophic scars
• Increased risk of organ and tissue rupture, especially in specific subtypes

Types of Ehlers-Danlos Syndrome

EDS is not a single disease but a spectrum of related disorders, each with its own unique genetic causes and clinical features. Accurate classification is essential for proper management, genetic counseling, and anticipating potential complications.

Type Name	Key Features	Genetic Basis/Inheritance	Source(s)
Classical	Skin hyperextensibility, atrophic scarring, joint hypermobility	COL5A1/COL5A2 mutations, autosomal dominant	5 7 9
Hypermobile	Generalized joint hypermobility, chronic pain, mild skin involvement	Unknown gene(s), autosomal dominant	5 7 10
Vascular	Thin, translucent skin, arterial/organ rupture, characteristic facial features	COL3A1 mutations, autosomal dominant	4 6 7 8 15
Kyphoscoliotic	Severe hypotonia, progressive scoliosis, scleral fragility	PLOD1 mutations, autosomal recessive	5 7 12
Arthrochalasia	Severe joint hypermobility, congenital hip dislocation	COL1A1/COL1A2 mutations, autosomal dominant	5 7 13
Dermatosparaxis	Extreme skin fragility, soft doughy skin	ADAMTS2 mutations, autosomal recessive	5 7 13
Rare Types	Variable symptoms, often overlap with others	Multiple genes, varied inheritance	7 9 11 13

Table 2: EDS Types by Features and Genetics

The 2017 International Classification

In 2017, an updated international classification recognized 13 distinct subtypes of EDS, reflecting advances in genetic research and a better understanding of clinical presentations 7. This replaced the earlier Villefranche nosology, which listed only six types. The most common types include:

Classical EDS

Characterized by skin hyperextensibility, atrophic (thin, papery) scarring, and joint hypermobility. Mutations in type V collagen genes (COL5A1, COL5A2) are most frequently responsible, and inheritance is typically autosomal dominant 5 7 9.

Hypermobile EDS (hEDS)

Probably the most common subtype, hEDS is defined by generalized joint hypermobility, chronic musculoskeletal pain, and mild skin involvement. Unlike other types, the genetic mutation causing hEDS remains unknown, making diagnosis solely clinical 5 7 10.

Vascular EDS (vEDS)

This life-threatening form is marked by translucent skin, visible veins, easy bruising, and a high risk of arterial, bowel, and uterine rupture. Mutations in the COL3A1 gene (type III collagen) are responsible. Most cases are autosomal dominant and can be inherited or occur as new mutations 4 6 7 8 15.

Other Subtypes

• Kyphoscoliotic EDS: Severe muscle weakness, early-onset scoliosis, scleral fragility; caused by mutations in PLOD1 5 7 12.
• Arthrochalasia EDS: Severe joint hypermobility, including congenital hip dislocation; linked to defects in type I collagen genes 5 7 13.
• Dermatosparaxis EDS: Marked by extreme skin fragility and soft, doughy skin; caused by ADAMTS2 mutations 5 7 13.
• Rare Variants: New subtypes continue to be discovered, often linked to mutations in other extracellular matrix proteins or enzymes 7 9 11 13.

The Importance of Subtype Identification

Determining the specific subtype is crucial, as complications and management strategies differ widely. For example, the vascular form requires urgent recognition due to its risk of sudden, catastrophic events 6 8 15, while hypermobile EDS is more focused on pain and functional management 1 10.

Causes of Ehlers-Danlos Syndrome

EDS is rooted in genetics, but the underlying defects are as varied as its clinical presentations. Understanding these causes is key to diagnosis, counseling, and the ongoing search for targeted therapies.

Cause	Description	Inheritance Pattern	Source(s)
Collagen Defects	Mutations in genes encoding types I, III, V collagen	Mostly autosomal dominant	4 5 6 7 9
Collagen-Modifying Enzyme Defects	Mutations in enzymes for collagen processing	Often autosomal recessive	4 7 12 13
Extracellular Matrix Protein Defects	Mutations in tenascin-X, others	Dominant or recessive	7 11 13
Unknown Genetic Mechanisms	Especially in hypermobile EDS	Autosomal dominant (suspected)	5 7 10

Table 3: Genetic Causes of EDS

Collagen and Connective Tissue

Most types of EDS are caused by mutations in genes responsible for the structure or processing of collagen—a key protein providing strength and elasticity to connective tissues. For example:

• Classical EDS: Mutations in COL5A1 or COL5A2 (type V collagen).
• Vascular EDS: Mutations in COL3A1 (type III collagen), critical for blood vessel integrity 4 6 7 9.
• Kyphoscoliotic EDS: Mutations in PLOD1, which encodes lysyl hydroxylase, an enzyme essential for collagen cross-linking 12.

Collagen-modifying enzyme defects can disrupt not just the protein structure but also its assembly and stability, leading to tissue fragility 4 7 12 13.

Other Extracellular Matrix Components

Beyond collagen, mutations have been identified in genes affecting other extracellular matrix proteins, such as tenascin-X (TNXB). Tenascin-X deficiency causes a recessive form of EDS with a distinct clinical profile, proving that EDS can arise from defects outside the classic collagen pathways 7 11 13.

Inheritance Patterns

• Autosomal dominant: Most common inheritance, seen in classical, hypermobile, vascular, and arthrochalasia types.
• Autosomal recessive: Seen in kyphoscoliotic, dermatosparaxis, and some rare subtypes (e.g., tenascin-X deficiency) 7 11 12 13.

The Mystery of Hypermobile EDS

Unlike other types, hypermobile EDS does not yet have a known genetic cause. Research continues, but diagnosis currently relies on clinical criteria, making it a unique challenge for patients and clinicians 5 7 10.

Treatment of Ehlers-Danlos Syndrome

Although there is currently no cure for EDS, a multidisciplinary approach can greatly improve quality of life and reduce the risk of complications. Treatment strategies are tailored to the type, severity, and specific manifestations in each individual.

Focus Area	Core Strategies	Notes/Impact	Source(s)
Pain Management	Physical therapy, medications, assistive devices	Individualized; essential for QOL	1 2 17
Vascular Complications	Blood pressure control, lifestyle modification, celiprolol	Critical in vEDS; reduces risk of rupture	6 8 14 15 16 18
Surveillance	Regular monitoring of organs, blood vessels	Early detection of complications	5 15 18
Surgery	Only when life-saving, with specialized teams	High risk due to tissue fragility	6 8 14 15 18
Genetic Counseling	Family risk assessment, prenatal advice	Informs family planning	7 8 9 15
Supportive Care	Occupational therapy, psychological support	Enhances coping and adaptation	1 5 17

Table 4: EDS Treatment Strategies

Pain Management and Physical Therapy

Chronic pain is one of the most disabling symptoms of EDS and requires a tailored, multimodal approach. Physical therapy focuses on strengthening muscles, improving joint stability, and preventing injury. Medications (analgesics, anti-inflammatories) are often used, but care must be taken to avoid overuse. Assistive devices—such as braces, cushions, and compression garments—can help support joints and reduce pain 1 2 17.

Management of Vascular Complications

For those with vascular EDS, the priority is preventing life-threatening events. Strategies include:

• Blood pressure control: Keeping blood pressure in the normal range minimizes stress on fragile vessels 6 15 16 18.
• Medication: Celiprolol, a beta-blocker, has shown promise in reducing arterial complications and improving survival in vEDS. Angiotensin II receptor blockers may also be used 16 18.
• Lifestyle modification: Avoiding contact sports, heavy lifting, and activities that increase the risk of trauma 15 18.
• Emergency planning: Patients should carry a “vascular EDS passport” detailing their diagnosis and emergency care plan 15.

Monitoring and Surveillance

Regular imaging (Doppler ultrasound, CT angiography, MRI) is recommended to monitor for aneurysms, arterial dissections, and organ complications—especially in high-risk subtypes 5 15 18.

Surgery and Invasive Procedures

Surgery is high-risk in EDS due to tissue fragility and poor wound healing. It should only be performed when absolutely necessary and by experienced teams familiar with EDS. Whenever possible, conservative management is preferred 6 8 14 15 18.

Genetic Counseling

Identifying the genetic mutation allows for accurate risk assessment in families and can inform prenatal testing. This is especially important for the vascular and other severe subtypes 7 8 9 15.

Supportive and Psychological Care

Living with EDS can be emotionally challenging. Access to occupational therapy, psychological support, and patient organizations can improve coping skills, social participation, and overall well-being 1 5 17.

Conclusion

Ehlers-Danlos Syndrome is a complex group of connective tissue disorders with a broad spectrum of symptoms, types, and risks. While there is no cure, advances in genetic understanding and multidisciplinary care are improving outcomes and quality of life for many people living with EDS.

Key points covered:

• EDS symptoms range from joint hypermobility and chronic pain to life-threatening vascular complications.
• There are at least 13 recognized types of EDS, each with distinct genetic causes and clinical features.
• Most forms are caused by mutations affecting collagen or related proteins and enzymes, with various inheritance patterns.
• Treatment is multidisciplinary, focusing on pain management, prevention of complications, genetic counseling, and supportive care.
• Early diagnosis and tailored management are essential to minimize risks and support patients in leading fulfilling lives.

If you or a loved one has EDS or suspects it, seeking care from an experienced, multidisciplinary team can make all the difference.