Ehlers-Danlos Syndrome (EDS) is a complex group of inherited conditions affecting connective tissue throughout the body. The history of observing its characteristic symptoms spans centuries, long before it was formally named. The journey from anecdotal accounts of unusual flexibility to a modern, genetically defined disorder illustrates a progression of medical understanding.
Defining Ehlers-Danlos Syndrome
Ehlers-Danlos Syndrome is caused by genetic defects that compromise the integrity of connective tissue, which serves as structural support throughout the body. The primary component affected is collagen, a protein responsible for providing tensile strength and elasticity to skin, joints, and blood vessels. Defects in the genes that produce or process collagen disrupt its normal structure or assembly. This results in the hallmark features of the syndrome: joint hypermobility, skin hyperextensibility, and tissue fragility.
The consequences of this faulty connective tissue are wide-ranging, leading to symptoms in multiple body systems. Individuals may experience frequent joint dislocations and chronic pain due to loose joints. The skin can be fragile, soft, bruise easily, and wound healing may be delayed, often leading to distinct, thin scars.
Precursors to Formal Recognition
Observations of people with extreme joint laxity and fragile skin predate the 20th-century naming of the syndrome by thousands of years. The Greek physician Hippocrates is credited with noting in 400 BC that certain nomadic groups, such as the Scythians, had loose joints and numerous scars.
In the 17th century, Dutch surgeon Job van Meek’ren documented the case of a Spanish boy named George Albes who could stretch the skin on his chin to his chest. This detailed description of extreme skin hyperextensibility provided a medical record, though it was not yet linked to any systemic disorder. Individuals with these traits, known as the “India Rubber Men,” performed feats of contortion and skin stretching in traveling shows during the 19th century. By 1892, Russian dermatologist Alexander Tschernogobow described a patient with skin fragility, elasticity, and joint hypermobility, providing a more systematic medical explanation.
The Contributions of Ehlers and Danlos
The formal recognition of the condition as a distinct clinical entity occurred at the turn of the 20th century through the separate work of two European physicians. In 1901, Danish dermatologist Edvard Ehlers presented findings on a patient who exhibited joint hypermobility, skin laxity, and a tendency toward easy bruising. Ehlers’s presentation brought these disparate symptoms together under a single medical description, moving the condition from anecdotal observation to clinical recognition.
In 1908, French physician Henri-Alexandre Danlos further contributed to the syndrome’s definition. Danlos focused on the cutaneous manifestations, describing the fragile, scarred skin and the formation of small, spongy outgrowths, sometimes called molluscoid pseudotumors. His work emphasized the tissue fragility component, particularly issues with wound healing and scarring. The syndrome was initially referred to by various names, such as cutis hyperelastica, until 1936, when English physician Frederick Parkes Weber proposed combining the two names to formally establish the eponym “Ehlers-Danlos Syndrome.”
The Shift to Modern Classification Systems
Following the initial descriptions, the understanding of EDS remained broad until the mid-20th century. Early classification attempts sought to organize the different presentations of the syndrome. A significant step in standardizing diagnosis was the Villefranche Nosology in 1997, which established six major subtypes based primarily on clinical criteria. This system provided clear diagnostic criteria, allowing for more consistent diagnosis and serving as the standard for two decades.
The discovery of underlying genetic causes drove the next major revision, leading to the 2017 International Classification. This modern system expanded the number of recognized EDS subtypes to 13, emphasizing genotype-phenotype correlation. For nearly all 13 types, definitive diagnosis relies on identifying a causative genetic variant, such as mutations in COL5A1 or COL3A1 genes. The only exception is hypermobile EDS (hEDS), the most common type, for which diagnosis still rests solely on clinical criteria. This evolution enables more precise diagnosis and targeted research.