Ehlers-Danlos syndromes (EDS) are a group of inherited disorders affecting the body’s connective tissue, which provides structure and support to skin, joints, blood vessels, and other organs. EDS is primarily characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Although formal medical recognition of EDS occurred relatively recently, the physical manifestations have been observed and documented for centuries. The history of EDS reflects an evolving understanding, shifting from anecdotal observations of flexibility to a highly specific, genetically defined classification of multiple distinct disorders.
Early Accounts of Skin and Joint Laxity
The unique physical traits associated with EDS were noted in historical records long before the condition was formally identified. Around 400 BCE, the ancient Greek physician Hippocrates observed individuals with features consistent with connective tissue disorders, such as weak joints and skin that scarred easily. These early descriptions show that the underlying characteristics of the syndrome have been present for millennia.
More detailed medical accounts began appearing in the 17th century, often as isolated case reports describing extreme skin elasticity or flexibility. These reports did not recognize the symptoms as part of a unified syndrome. By the late 19th century, individuals with notable hyperextensibility and flexibility gained notoriety as performers in traveling shows, advertised with titles like “The India Rubber Man.” Formal medical documentation increased during this time, notably when Russian dermatologist Alexandre Nicolaiev Tschernogobov described two patients with loose, fragile skin and hypermobile joints in 1892.
The Contributions of Ehlers and Danlos
The syndrome received its name from two European physicians who published influential case studies at the turn of the 20th century. In 1901, Danish dermatologist Edvard Ehlers presented a detailed case study of a patient exhibiting hyperelastic skin, bruising, and frequently dislocating joints. Ehlers’ work was significant because it unified these disparate symptoms—joint laxity, skin hyperextensibility, and tissue fragility—as a distinct clinical entity.
In 1908, French physician Henri-Alexandre Danlos independently contributed to the understanding of the disorder. Danlos published a report focusing on the remarkable extensibility and fragility of the skin, proposing these were the primary features of the syndrome. Although Ehlers and Danlos published separately, their combined observations outlined the major defining features of the condition. The name “Ehlers-Danlos syndrome” was formally applied in 1936, when English physician Frederick Parkes-Weber suggested the eponym to recognize their foundational work.
Formalizing the Syndrome and Initial Criteria
Following the naming of the syndrome, the medical community began the process of formalizing diagnostic criteria and classifying the different presentations. Classification of EDS began in the late 1960s, a period when the first molecular defects were also being identified. Initial categorization attempts, such as the 1986 Berlin nosology, used Roman numerals (e.g., EDS Type I through XI) based largely on observable clinical symptoms and inheritance patterns.
The most significant step in early formalization was the 1997 conference in Villefranche, France, which produced the Villefranche Nosology, published in 1998. This system simplified the classification to six major types, using descriptive names like Classical, Hypermobility, and Vascular EDS instead of Roman numerals. The Villefranche criteria established standardized major and minor clinical features for each type. This nosology served as the international standard for nearly two decades, bringing uniformity to diagnosis.
The Modern Era of Classification
Understanding EDS advanced rapidly, driven by scientific progress in genetics. The most recent and comprehensive update was the 2017 International Classification of the Ehlers-Danlos Syndromes. This new nosology reorganized the disorders into 13 distinct subtypes. The core purpose of the 2017 classification was to shift the diagnostic focus from clinical observation to genetic identification.
For nearly all 13 subtypes, a definitive diagnosis now requires molecular confirmation through genetic testing to identify the specific causative gene mutation. These mutations involve genes responsible for producing or modifying collagen and other connective tissue proteins. The notable exception is Hypermobile EDS (hEDS), the most common type, which remains a purely clinical diagnosis because its underlying genetic cause is unknown. The 2017 update established new, stringent clinical criteria for hEDS to distinguish it from other forms of generalized joint hypermobility.