Ehlers-Danlos syndrome (EDS) is a group of genetic disorders that affect connective tissues, which provide strength and elasticity to structures such as skin, joints, and blood vessel walls. The condition is characterized by joint hypermobility, skin hyperextensibility, and tissue fragility.

The syndrome was first described in the early 20th century by two separate physicians: Edvard Ehlers from Denmark in 1901, and Henri-Alexandre Danlos from France in 1908. Ehlers initially presented a case of a patient with skin that was unusually extensible and bruised easily. Danlos later described a similar patient, emphasizing the skin’s elasticity and tendency to bruise. Their combined observations laid the groundwork for what would eventually be known as Ehlers-Danlos syndrome.

Over time, as more cases were studied, it became clear that EDS was not a single disorder but a variety of conditions with differences in genetic causes and manifestations. By the mid-20th century, researchers began to classify these variations. In 1988, a major classification was established that identified several types of EDS, primarily based on symptoms and genetic causes.

The most recent major revision of the EDS classification came in 2017, when the International Consortium on the Ehlers-Danlos Syndromes and Related Disorders updated the diagnostic criteria and classifications. This revision recognizes 13 subtypes of EDS, each associated with different genetic markers and clinical presentations. This update reflects advances in genetic research and a better understanding of the disorder’s molecular basis.

Current State and Research
Today, research into EDS is focused on understanding the varied genetic causes and mechanisms of the syndrome to develop more effective treatments. There is no cure for EDS, and treatment remains elusive for many, focusing on managing symptoms and preventing complications. This includes physical therapy, pain management, and, in some cases, surgery to repair damaged joints or tissues.

Awareness of EDS has grown, and diagnostic methods have improved, but many challenges remain in ensuring timely and accurate diagnosis and in providing comprehensive care. Research continues into the genetics of EDS as well as into strategies to improve quality of life for those affected by the syndrome.

To date, there is no genetic testing available for hypermobile EDS, verified by the Mayo Clinic. One of the hottest and most needed areas of genetic research is in the area of Hypermobile EDS (hEDS) as it is the only type not yet identified by a gene, but that is changing. Follow the progress of the Medical University at South Carolina (MUSC) and their Norris Lab, who are on the hunt for the genetic cause of hEDS. Led by Chip Norris, PhD and the EDS influencer and patient Cortney Gensemer, PhD, they first announced the news in a 2021 press release and also recently pre-announced their research findings on the gene family they discovered in their data, which is the largest patient DNA registry in the world for EDS. There is controversy in the EDS community about the value of pushing ahead to publish their paper without a traditional peer-review process first and the validity questions this strategy brings. But many patients and families desperately seeking solutions are thrilled with the news that an answer is on the horizon for a potential simple blood test to diagnose hEDS.

Researchers at the Norris Lab conducted the study looking for genetic links to hEDS by sequencing the DNA of families and individuals with hEDS. They discovered a specific change (variant) in the KLK15 gene that was associated with hEDS in two families. The KLK15 gene provides instructions for making a protein called kallikrein-15. To test what happens when this specific KLK15 genetic variant is present, the team created mice with an equivalent KLK15 variant. Six mice were studied and most had similar connective tissue problems to those seen in hEDS patients, such as weaker tendons and heart valve issues. It suggests that this KLK15 variant could play a role in causing hEDS in some people. A further analysis of 197 hEDS patients also showed that 65 (one third) had at least one kallikrein gene variant from within the whole family of kallikrein genes. This raises the possibility that other kallikrein gene variants may also be involved, but further work needs to be done to explore this.