Ehlers-Danlos Syndrome (EDS) is a collection of inherited disorders that affect the body’s connective tissue, the biological material providing support and structure to many parts of the body. This group of systemic conditions impacts tissues throughout the body, leading to a wide range of signs that vary significantly between individuals. EDS is a chronic condition characterized by varying degrees of joint instability, skin differences, and general tissue fragility. The overall frequency of all Ehlers-Danlos syndromes is estimated to be around 1 in 5,000 people.
The Role of Connective Tissue
Connective tissue is the framework that supports, connects, or separates different types of tissues and organs. This material, made up of cells, fibers, and a ground substance, provides structure, strength, and elasticity throughout the body. The fibers, primarily composed of proteins like collagen and elastin, are responsible for the tissue’s ability to resist stretching and return to its original shape.
Ehlers-Danlos syndromes arise from genetic changes that affect the structure or processing of these proteins, most commonly collagen. Collagen is the most abundant protein in the human body, providing tensile strength to skin, tendons, ligaments, blood vessel walls, and organs. When genetic instructions for making or modifying collagen are altered, the resulting protein is faulty or insufficient, which weakens the connective tissue framework. This weakness explains the characteristic fragility and hyperextensibility seen in EDS. Genetic variants are typically inherited in an autosomal dominant or recessive pattern, though some cases result from a new, spontaneous genetic change.
The Major Types of Ehlers-Danlos Syndrome
The Ehlers-Danlos syndromes are classified into 13 distinct subtypes based on the 2017 international classification. Hypermobile Ehlers-Danlos Syndrome (hEDS) is the most prevalent, accounting for an estimated 90% of all EDS cases. Unlike most other types, the specific genetic cause for hEDS remains unknown, and its diagnosis is based purely on clinical criteria. People with hEDS experience significant generalized joint hypermobility, often leading to instability, chronic pain, and fatigue.
Classical Ehlers-Danlos Syndrome (cEDS) is much less common, affecting roughly 1 in 20,000 to 40,000 people, and is typically caused by genetic variants in the COL5A1 or COL5A2 genes, which affect Type V collagen. Defining features of cEDS include marked skin hyperextensibility, velvety skin texture, generalized joint hypermobility, and the formation of characteristic widened, atrophic scars. Vascular Ehlers-Danlos Syndrome (vEDS) is considered the most serious type due to its potential for life-threatening complications. This type is caused by variants in the COL3A1 gene, which affects Type III collagen, a protein abundant in blood vessels and hollow organs.
The faulty Type III collagen in vEDS leads to extreme fragility of arteries, intestines, and the uterus, significantly increasing the risk of spontaneous rupture or dissection of major blood vessels. The other ten types, such as Kyphoscoliotic EDS (kEDS) and Dermatosparaxis EDS (dEDS), are considered ultra-rare. The specific type of EDS dictates the potential complications, the genetic inheritance pattern, and the necessary management approach.
Key Signs and Symptoms
The manifestations of Ehlers-Danlos syndrome are widespread because connective tissue is present throughout the entire body. The most recognizable characteristic is generalized joint hypermobility, meaning joints can move beyond the typical range of motion. This hypermobility often leads to joint instability, frequent partial dislocations (subluxations), and full dislocations that can occur without significant trauma. The chronic strain on the musculoskeletal system due to unstable joints frequently results in persistent and widespread pain and debilitating fatigue.
Another defining feature is skin hyperextensibility, where the skin can be stretched much farther than normal and often feels soft and velvety to the touch. This fragility makes the skin prone to easy bruising and poor wound healing, sometimes leading to characteristic thin, widened scars. Beyond the joints and skin, EDS can affect other body systems, with common associated issues including digestive problems, such as irritable bowel syndrome (IBS), and cardiovascular concerns, such as mitral valve prolapse. Some people also experience autonomic nervous system dysfunction, which can cause symptoms like dizziness and a rapid heart rate upon standing.
Diagnosis and Management Approaches
Diagnosis of Ehlers-Danlos syndrome involves a comprehensive clinical evaluation, often by a medical geneticist. The process utilizes established criteria, such as the 2017 international classification, which provides specific guidelines for each of the 13 subtypes. For hypermobile EDS (hEDS), which lacks a known genetic marker, the diagnosis is made entirely clinically, requiring the presence of generalized joint hypermobility, systemic manifestations, and the exclusion of other diagnoses.
For all other types of EDS, clinical suspicion based on the physical examination and family history is typically confirmed through molecular genetic testing. This testing identifies the specific genetic variant responsible for the condition, which is crucial for accurate diagnosis and genetic counseling. Because EDS is a condition resulting from an inherent tissue defect, there is no cure, so management is focused on supportive and preventative care.
A multidisciplinary team approach is generally recommended, involving specialists such as physical therapists, pain management physicians, and occupational therapists. Physical therapy is utilized to strengthen the muscles surrounding joints, providing external stability to compensate for the weak connective tissue. Management also includes strategies to minimize injury, address chronic pain, and monitor for specific complications, such as regular cardiovascular screenings for individuals with vascular EDS.