Ehlers–Danlos syndromes (EDS) are a group of 13 genetic connective-tissue disorders in the current classification, with a 14th type discovered in 2018. Symptoms include loose joints, joint pain, stretchy velvety skin, and abnormal scar formation. These may be noticed at birth or in early childhood. Complications may include aortic dissection, joint dislocations, scoliosis, chronic pain, or early osteoarthritis.EDS occurs due to variations of more than 19 genes that are present at birth. The specific gene affected determines the type of EDS. Some cases result from a new variation occurring during early development, while others are inherited in an autosomal dominant or recessive manner. Typically, these variations result in defects in the structure or processing of the protein collagen.Diagnosis is often based on symptoms and confirmed by genetic testing or skin biopsy, but people may initially be misdiagnosed with hypochondriasis, depression, or chronic fatigue syndrome.No cure is known and treatment is supportive in nature. Physical therapy and bracing may help strengthen muscles and support joints. Some forms of EDS result in a normal life expectancy, but those that affect blood vessels generally decrease it.The hypermobile type of EDS (hEDS) affects at least one in 5,000 people globally; other types occur at lower frequencies. The prognosis depends on the specific disorder. Excess mobility was first described by Hippocrates in 400 BC. The syndromes are named after two physicians, Edvard Ehlers and Henri-Alexandre Danlos, who described them at the turn of the 20th century. Types
In 2017, 13 subtypes of EDS were classified using specific diagnostic criteria.
Another way the Norris lab is attempting to find this gene is by looking at genes involved in the formation of the aorta and mitral valves, as these valves are often prolapsed or malformed as a symptom of EDS. Because hEDS is such a complex, multi-organ disease, focusing on one hallmark trait has proven successful. One gene found this way is DZIP1, which regulates cardiac valve development in mammals through a Cby1-beta-catenin mechanism. Mutations at this gene affect the beta-catenin cascade involved in development, causing malformation of the extra-cellular matrix, resulting in loss of collagen. A lack of collagen here is both consistent with hEDS and explains the "floppy" mitral and aortic valve heart defects. A second genetic study specific to mitral valve prolapse focused on the PDGF signaling pathway, which is involved in growth factor ligands and receptor isoforms. Mutations in this pathway affect the ability to localize cilia in various cell types, including cardiac cells. With the resulting ciliopathies, structures such as the cardiac outflow tract, heart tube assembly, and cardiac fusion are limited and/or damaged. Classical EDS
Classical EDS (formerly categorized as type 1) is characterized by extremely elastic skin that is fragile and bruises easily and hypermobility of the joints. Molluscoid pseudotumors (calcified hematomas that occur over pressure points) and spheroids (cysts that contain fat occurring over forearms and shins) are also often seen. A side complication of the hyperelasticity presented in many EDS cases makes wounds closing on their own more difficult. Sometimes, motor development is delayed and hypotonia occurs.