[1] Diagnosis is often based on symptoms and confirmed by genetic testing or skin biopsy, particularly with hypermobile EDS (hEDS), but people may initially be misdiagnosed with hypochondriasis, depression, or myalgic encephalomyelitis/chronic fatigue syndrome.

In general, people with this variant have skin that is soft, smooth, and velvety and bruises easily, and may have chronic muscle or bone pain.

Some possible complications are pre-labor rupture of membranes, a drop in blood pressure with anesthesia, precipitated birth (very fast, active labor), malposition of the fetus, and increased bleeding.

[23] Using CRISPR Cas-9 mediated genome editing on mouse models of the disease, the lab has recently identified a "very strong candidate gene"[24] for hEDS.

This finding, and a greater understanding of cardiac complications associated with the majority of EDS subtypes, has led to the development of multiple druggable pathways involved in aortic and mitral valve diseases.

In 35 families, copy number alterations in TPSAB1,[26] encoding alpha-tryptase, were associated with increased basal serum tryptase levels, associated with autonomic dysfunction, gastrointestinal disorders, allergic and cutaneous symptoms, and connective tissue abnormalities, all concurrent with hEDS phenotype.

Mutations at this gene affect the beta-catenin cascade involved in development, causing malformation of the extracellular matrix, resulting in loss of collagen.

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.

[29] Without genetic testing, healthcare professionals may be able to provide a provisional diagnosis based on careful examination of the mouth, skin, and bones, as well as by neurological assessment.

It also has characteristic facial features, including large eyes, an undersized chin, sunken cheeks, a thin nose and lips, and ears without lobes.

People may also have easy bruising, fragile arteries that are prone to rupture, unusually small corneas, and osteopenia (low bone density).

Other common features include fragile, elastic skin with easy bruising, hypotonia, kyphoscoliosis (kyphosis and scoliosis), and mild osteopenia.

[8] Spondylodysplastic EDS is characterized by short stature (progressive in childhood), muscle hypotonia (ranging from severe congenital to mild later-onset), and bowing of limbs.

However, as connective tissue is found throughout the body, EDS may result in an array of unexpected impacts with any degree of severity, and the condition is not limited to joints, skin, and blood vessels.

[45][56] Other skin symptoms include molluscoid pseudotumors,[57] especially on pressure points, petechiae,[58] subcutaneous spheroids,[57] livedo reticularis; piezogenic papules are less common.

[70] Excessive menstrual bleeding can sometimes be attributed to inappropriate platelet aggregation, but faulty collagen leads to weakened capillary walls which increase the likelihood of hemorrhage.

[71] Post-partum hemorrhage and maternal injury such as sporadic pelvic displacement, hip dislocation, torn and stretched ligaments, and skin tearing can all be linked to altered structure of connective tissues.

Although research in this area is sparse, patients with joint hypermobility were found to have higher rates of indirect hyperbilirubinemia than control groups.

[83] Splanchnic circulation, small fiber neuropathy and altered vascular compliance have all been named as potential contributors to gastrointestinal complaints,[85] particularly for patients who have a known, comorbid autonomic condition.

[89] Increased pressure created by the malformation can lead to a flattened pituitary gland, hormone changes, sudden severe headaches, ataxia, and poor proprioception.

[90] Ophthalmological manifestations include nearsightedness, retinal tearing and retinal detachment, keratoconus, blue sclera, dry eye, Sjogren's syndrome, lens subluxation, angioid streaks, epicanthal folds, strabismus, corneal scarring, brittle cornea syndrome, cataracts, carotid-cavernous sinus fistulas, and macular degeneration.

People with a "marfanoid" appearance are often tall and thin with long arms and legs and "spidery" fingers while EDS phenotypes vary considerably.

Instability of almost all joints can happen, but appears most often in the lower and upper extremities, with the wrist, fingers, shoulder, knee, hip, and ankle being most common.

[119] If considering surgical intervention, seeking care from a surgeon with extensive knowledge and experience in treating people with EDS and joint hypermobility issues would be prudent.

Those with blood vessel fragility, though, have a high risk of fatal complications, including spontaneous arterial rupture, which is the most common cause of sudden death.

One review, of a pediatric EDS clinic in the American Midwest between 2020 and 2022, found that 17% of patients identified as trans or gender-diverse, 89% of whom were assigned female at birth.

[136] Meanwhile, a 2020 analysis found that among adults undergoing gender-affirming surgery, 2.6% had a diagnosis of EDS—130 times the highest reported prevalence of EDS in the general population.

[138] Forms of EDS in this category may present with soft, mildly stretchable skin, shortened bones, chronic diarrhea, joint hypermobility and dislocation, bladder rupture, or poor wound healing.

Contortionist Daniel Browning Smith has hypermobile EDS and holds the current Guinness World Record for the most flexible man as of 2018, while Gary "Stretch" Turner, sideshow performer in the Circus Of Horrors, has held the current Guinness World Record for the most elastic skin since 1999, for his ability to stretch the skin on his stomach 6.25 inches.

[141] The fantasy novel Fourth Wing by Rebecca Yarros presents a main character, Violet Sorrengail, who has an unnamed chronic condition that aligns closely with EDS symptoms.