This form is the most common and ONLY form without a specific causative genetic change identified. Symptoms of generalized joint hypermobility do not immediately cause pathogenic effects, but rather instability within the joints over time causes progressive symptoms of joint pain due to tears and microtraumas promoting chronic inflammation. The severity of this pain is often the primary reason patients seek medical help. Symptoms experienced by patients can include autonomic nervous system dysfunction, also called dysautonomia, functional gastrointestinal disorders (FGIDs), Celiac Disease, Mast Cell Activation Disorder (MCAD), all of which contribute to severe fatigue. Musculoskeletal and rheumatic complications can further include subluxation, dislocations, tears, sprains, osteopenia, osteoarthritis, and cranio-cervical instability.

This is currently not classified under the EDS category, but is clinically almost indistinguishable from hEDS and current agreement on the division of HSD from hEDS is controversial. Patients with HSD have no less severe symptoms, pain, or disability than those with hEDS and care guidelines and recommendations are exactly the same. Therefore we include HSD in this categorization for a patient focused resource that fosters that understanding.

This is the second most common form of EDS. The major criteria are skin hyperextensibility, atrophic scars, and joint hypermobility, while the minor criteria include easy bruising, skin involvement, hernias, epicanthal folds, and an affected first degree relative. Patients satisfying the main diagnostic criteria for cEDS have seen over 90% positive results for the genetic changes in either genes that cause the disorder: COL5A1 or COL5A2. Very rarely, changes in the gene COL1A1 can cause cEDS.

The presentation of this form is very similar to cEDS, hence the name. In this form, the altered gene for tenascin-X, TNXB, is disrupted. It plays a crucial role in supporting the scaffold of collagen and elastin, so even though it's a different gene, the expression of symptoms is very similar to cEDS and can only be differentiating through confirmatory testing of TNXB. Molecular analysis of TNXB can be difficult due to the presence of a pseudogene, which can warrant additional Sanger sequencing for confirmation.

The newest EDS Diagnostic Guide was released in 2017, but the most recent form of EDS identified was in 2018, less than a year after the updates were made. cl2EDS was identified in several families of unrelated patients presenting with a recognizable connective tissue disorder that falls in the EDS spectrum with joint hypermobility, skin laxity, delayed wound healing, abnormal scarring, aortic dilation, and osteoporosis. The identified gene, AEBP1, encodes the protein ACLP, which is expressed within the skin, vasculature, and other connective tissues playing a critical role in cellular maintenance and tissue repair.

Vascular EDS is often considered the most severe form of EDS due to the risk for fatal arterial rupture and other serious complications. Collagen III is the gene implicated in vEDS and compared to collagen I, it produces small-diameter fibrils that comprise about 5-20% of all human collagen and provides tensile strength and integrity to the major blood vessels of the hollow organs. vEDS is only confirmed through genetic testing and is likely underdiagnosed, with estimates of 1500 diagnosed cases in the United States.

Cardiac-valvular EDS is an extremely rare form of EDS, as of 2017 there were an estimated six patients identified with documented biallelic autosomal recessive variants in COL1A2. At its worst, the weakening of tissue can result in fatal ruptures of the aorta or mitral valve. While the descriptions focus on the severe consequences on the tissue that results from the complete absence of the alpha-2 chain of collagen I, the characterization of the expression of this condition based on the sample size alone is diverse. Patients with these conditions have reported overlapping phenotypes with Osteogenesis Imperfecta, cEDS, vEDS, hEDS, and other conditions with severe cardiac manifestations. Although extremely rare, ruling out variations within COL1A2 can prevent unexpected fatal outcomes from cardiac valvular fragility.

This form is caused by changes to either the COL1A1 or COL1A2 gene. It is very rare and typically diagnosed after confirmatory molecular testing at birth. It presents with congenital hip dislocations, fragile skin, scoliosis, and other developmental delays.

This condition is very rare and is caused by changes in the ADAMTS2 gene. Patients tend to share characteristic body features: short stature, blue sclera, and organ herniation that can cause severe complications along with extreme skin fragility. Milder phenotypes have been recently indicated clinically, but because everyone is different it is critical to have a molecular diagnosis via genetic testing.

Caused by changes in COL12A1. Extremely rare form characterized by congenital muscle weakness and atrophy that improves with age. There is an increased risk of joint contractor and hypermobility, delayed motor development, and atrophic scarring. Muscle biopsies reveal myopathy. Molecular testing of the Collagen 12 gene is required for confirmatory testing.

Fewer than 50 documented cases of this condition have shown that very specific changes to the CHST14/D4ST1 genes or the DSE gene cause this condition. This form has a characteristic facial appearance and a progressive tissue fragility concern.

This disorder can be caused by a few different genetic changes. Variants within B4GALT7-spEDS and B3GALT6-spEDS are defined as Linkeropathies, a rare and poorly characterized group of enzymatic disorders often presenting with short stature, skeletal dysplasia, joint laxity, heart malformations, and other broad manifestations throughout the body. Another form of spEDS occurs when the SLC39A13 gene is interrupted impacting the ZIP13 protein concentration. SLC39A13-spEDS has a more moderate expression of short stature, but still includes characteristic skeletal and skin symptoms of the other spEDS subtypes.

This condition is caused by changes in either PLOD1 or FKBP14 genes. It is very rare and typically diagnosed at birth. The resulting symptoms are often severe resulting in scleral fragility and poor eye health, severe muscular weakness, and potentially debilitating and progressive scoliosis.

The genes C1R and C1S are both heavily involved in the complement system, which is utilized by the immune system. Variants interfering with the function of this system results in inflammation in the tissue surrounding the teeth that can result in destruction of the gums and premature tooth loss beginning in early childhood.

This syndrome primarily impacts the connective tissue of the eyes. Ocular symptoms can overlap with symptoms of kEDS, Marfan Syndrome, aEDS, and Loeys-Dietz Syndrome.