Ehlers-Danlos Syndromes (EDS) are a complex group of inherited disorders affecting the body’s connective tissue, the structural framework that supports and connects organs and other tissues. This collection of 13 recognized subtypes is characterized by a fundamental defect in the body’s ability to produce or process proteins that provide strength and elasticity. Because connective tissue is pervasive throughout the body, symptoms are highly varied, affecting the skin, joints, blood vessels, and internal organs. The severity of EDS ranges significantly, from mild joint hypermobility to life-threatening vascular complications.
The Role of Collagen and Genetics
The root cause of Ehlers-Danlos Syndromes lies in faulty genes that govern the production and structure of collagen, the most abundant protein in the human body. Collagen acts as the body’s scaffolding, providing tensile strength and structure to the skin, tendons, ligaments, blood vessels, and bones. Genetic variations cause the body to produce collagen that is structurally weak, disorganized, or insufficient, resulting in connective tissue that is too stretchy and fragile.
These genetic changes are typically inherited, following either an autosomal dominant or autosomal recessive pattern, depending on the specific EDS type. For example, classical EDS is often linked to variations in the COL5A1 or COL5A2 genes, which code for Type V collagen. Although the specific gene causing hypermobile EDS (hEDS) remains unknown, most other types have identifiable genetic markers, such as the COL3A1 gene mutation associated with vascular EDS. These genetic defects result in a widespread decrease in the integrity of the extracellular matrix.
Recognizing the Different Types of EDS
The current classification, updated in 2017, recognizes 13 distinct subtypes of Ehlers-Danlos Syndrome, each defined by specific clinical features and, in almost all cases, a known genetic cause. Hypermobile EDS (hEDS) is the most common type, accounting for an estimated 80% to 90% of all EDS cases. The diagnostic criteria for hEDS are strictly clinical, as the causative gene or genes have not yet been identified.
Classical EDS (cEDS) is considerably rarer and is primarily characterized by marked skin hyperextensibility, velvety skin texture, and wide, atrophic scarring. This type is typically caused by variations in the COL5A1 and COL5A2 genes, which affect Type V collagen. The most serious type is Vascular EDS (vEDS), associated with a high risk of spontaneous rupture of arteries, intestines, and the uterus during pregnancy.
Vascular EDS is most often caused by mutations in the COL3A1 gene, leading to defects in Type III collagen, a protein highly concentrated in the walls of blood vessels and hollow organs. The remaining ten types of EDS are classified as ultra-rare. These rarer types include Kyphoscoliotic EDS (kEDS) and Arthrochalasia EDS (aEDS), each having unique features and distinct genetic mutations.
Clinical Features and Diagnostic Criteria
The clinical presentation of Ehlers-Danlos Syndromes is marked by a triad of symptoms: generalized joint hypermobility, skin hyperextensibility, and tissue fragility. Joint hypermobility manifests as an increased range of motion, often leading to chronic joint instability, frequent subluxations, and full dislocations. This joint instability is a major source of chronic, widespread musculoskeletal pain, as muscles work harder to compensate for lax ligaments.
Skin features commonly include a soft, velvety texture, easy bruising, and a tendency for wounds to heal slowly, leaving behind characteristic wide, “cigarette-paper” scars. Beyond the joints and skin, EDS is often associated with systemic issues, such as dysautonomia, gastrointestinal complications, and pelvic floor prolapse. Many individuals experience Postural Orthostatic Tachycardia Syndrome (POTS), which causes dizziness and an increased heart rate upon standing.
Diagnosis for all types of EDS, except hEDS, relies on clinical criteria followed by molecular confirmation through genetic testing. The diagnosis of hEDS is purely clinical and requires meeting a set of criteria updated in 2017, which assesses for generalized joint hypermobility using the Beighton Score. The Beighton Score is a nine-point system that evaluates the flexibility of the small and large joints. A confirmed hEDS diagnosis also requires the presence of other systemic features and the exclusion of all other types of EDS.
Strategies for Symptom Management
Since there is no cure for Ehlers-Danlos Syndromes, management focuses on a multidisciplinary approach to alleviate symptoms, improve function, and prevent complications. Physical therapy is a primary intervention, concentrating on exercises to increase muscle tone and strengthen the muscles surrounding unstable joints. Therapists emphasize low-impact activities, such as swimming or cycling, while avoiding joint-stretching exercises that could increase instability.
Managing chronic pain is a major component of care, often requiring a combination of pharmacological and non-pharmacological methods, including cognitive behavioral therapy and specialized pain management techniques. For systemic issues, such as dysautonomia, strategies often involve maintaining adequate hydration and increasing salt intake to manage blood pressure and heart rate. Patients with vEDS require proactive monitoring by specialists, such as cardiologists, to regularly screen for arterial aneurysms or dissections.
Occupational therapy can help individuals manage daily activities by providing adaptive equipment and techniques to protect fragile joints. Overall care involves a team of specialists, including geneticists, rheumatologists, cardiologists, and gastroenterologists, working to address the wide range of symptoms. The goal of this comprehensive management is to maximize quality of life and minimize injury risk.