Ehlers–Danlos syndrome

In 2017, 13 subtypes of EDS were classified using specific diagnostic criteria. According to the Ehlers–Danlos Society, the syndromes can also be grouped by the symptoms determined by specific gene mutations. Group A disorders are those that affect primary collagen structure and processing. Group B disorders affect collagen folding and crosslinking. Group C are disorders of structure and function of myomatrix. Group D disorders are those that affect glycosaminoglycan biosynthesis. Group E disorders are characterized by defects in the complement pathway. Group F are disorders of intracellular processes, and Group G is considered to be unresolved forms of EDS.{{cite web|url=https://www.ehlers-danlos.com/eds-types/|title=The Types of EDS|website=The Ehlers Danlos Society|access-date=2019-11-06}}

File:PMC3504533 1471-2415-12-47-2 (cropped).png

Classical EDS 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.{{cite web|title=Ehlers–Danlos syndromes | work = Genetic and Rare Diseases Information Center (GARD) – an NCATS Program | publisher = U.S. National Institutes of Health |url=https://rarediseases.info.nih.gov/diseases/6322/ehlers-danlos-syndromes |access-date=23 September 2017|date=20 April 2017|url-status=live|archive-url=https://web.archive.org/web/20170924001628/https://rarediseases.info.nih.gov/diseases/6322/ehlers-danlos-syndromes|archive-date=24 September 2017}}{{PD-notice}} The variation causing this type of EDS is in the genes COL5A2, COL5A1, and less frequently COL1A1. It involves the skin more than hEDS.{{cite book | vauthors = Malfait F, Wenstrup R, De Paepe A | chapter = Classic Ehlers–Danlos Syndrome| date = July 2018 | chapter-url= http://www.ncbi.nlm.nih.gov/books/NBK1244/| title = GeneReviews |publisher=University of Washington, Seattle |pmid=20301422 |access-date=2019-06-03 | veditors = Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K, Amemiya A}} In classical EDS, large variation in symptom presentation is seen. Because of this variance, EDS has often been underdiagnosed.{{cite journal | vauthors = Kapferer-Seebacher I, Lundberg P, Malfait F, Zschocke J | title = Periodontal manifestations of Ehlers–Danlos syndromes: A systematic review | journal = Journal of Clinical Periodontology | volume = 44 | issue = 11 | pages = 1088–1100 | date = November 2017 | pmid = 28836281 | doi = 10.1111/jcpe.12807 | s2cid = 36252998}} 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.{{cite journal | vauthors = Castori M | title = Ehlers–Danlos syndrome, hypermobility type: an underdiagnosed hereditary connective tissue disorder with mucocutaneous, articular, and systemic manifestations | journal = ISRN Dermatology | volume = 2012 | page = 751768 | date = 2012 | pmid = 23227356 | doi = 10.5402/2012/751768 | pmc = 3512326 | doi-access = free}}

A good way to begin the diagnostic process is by reviewing a person's family history. EDS is an autosomal dominant condition, so is often inherited from parents. Genetic testing remains the most reliable way to diagnose EDS.{{cite journal | vauthors = Rakhmanov Y, Maltese PE, Bruson A, Castori M, Beccari T, Dundar M, Bertelli M |date=2018-09-01|title=Genetic testing for vascular Ehlers–Danlos syndrome and other variants with fragility of the middle arteries|url=https://doaj.org/|journal=The EuroBiotech Journal|volume=2|issue=s1|pages=42–44|doi=10.2478/ebtj-2018-0034|s2cid=86589984|issn=2564-615X|doi-access=free}} No cure for type 1 EDS has been found, but a course of non-weight-bearing exercise can help with muscular tension, which can help correct some EDS symptoms. Anti-inflammatory drugs and lifestyle changes can help with joint pain. Lifestyle choices should also be made with children who have EDS to try to prevent wounds to the skin. Protective garments can help with this. In a wound, deep stitches are often used and left in place for longer than normal.

Classical-like EDS (clEDS) is characterized by skin hyperextensibility with velvety skin texture and absence of atrophic scarring, generalized joint hypermobility with or without recurrent dislocations (most often shoulder and ankle), and easily bruised skin or spontaneous ecchymoses (discolorations of the skin resulting from bleeding underneath). It can be caused by variations in the TNXB gene.

Arthrochalasia EDS (aEDS; formerly categorized as types 7A and B) is characterized by severe joint hypermobility and congenital hip dislocation. Other common features include fragile, elastic skin with easy bruising, hypotonia, kyphoscoliosis (kyphosis and scoliosis), and mild osteopenia. Type-I collagen is usually affected. It is very rare, with about 30 cases reported. It is more severe than the hypermobility type. Variations in the genes COL1A1 and COL1A2 cause it.{{cite journal | vauthors = Klaassens M, Reinstein E, Hilhorst-Hofstee Y, Schrander JJ, Malfait F, Staal H, ten Have LC, Blaauw J, Roggeveen HC, Krakow D, De Paepe A, van Steensel MA, Pals G, Graham JM, Schrander-Stumpel CT | title = Ehlers–Danlos arthrochalasia type (VIIA-B) – expanding the phenotype: from prenatal life through adulthood | journal = Clinical Genetics | volume = 82 | issue = 2 | pages = 121–130 | date = August 2012 | pmid = 21801164 | pmc = 4026000 | doi = 10.1111/j.1399-0004.2011.01758.x}}

Brittle-cornea syndrome (BCS) is characterized by the progressive thinning of the cornea, early-onset progressive keratoglobus or keratoconus, nearsightedness, hearing loss, and blue sclerae.{{cite web|url=https://rarediseases.info.nih.gov/diseases/1019/brittle-cornea-syndrome|title=Brittle cornea syndrome | work = Genetic and Rare Diseases Information Center (GARD) – an NCATS Program | publisher = U.S. National Institutes of Health |access-date=2019-06-03}} Classic symptoms, such as hypermobile joints and hyperelastic skin, are also seen often.{{cite web|url=https://www.omim.org/entry/614170|title=OMIM Entry – # 614170 – Brittle Cornea Syndrome 2; BCS2|website=www.omim.org|access-date=2018-06-18}} It has two types. Type 1 occurs due to variations in the ZNF469 gene. Type 2 is due to variations in the PRDM5 gene.

Cardiac-valvular EDS (cvEDS) is characterized by three major criteria: severe progressive cardiac-valvular problems (affecting aortic and mitral valves), skin problems such as hyperextensibility, atrophic scarring, thin skin, and easy bruising, and joint hypermobility (generalized or restricted to small joints). Four minor criteria may aid in the diagnosis of cvEDS. cvEDS is an autosomal recessive disorder, inherited through variation in both alleles of the gene COL1A2.{{cite journal | vauthors = Guarnieri V, Morlino S, Di Stolfo G, Mastroianno S, Mazza T, Castori M | title = Cardiac valvular Ehlers–Danlos syndrome is a well-defined condition due to recessive null variants in COL1A2 | journal = American Journal of Medical Genetics. Part A | volume = 179 | issue = 5 | pages = 846–851 | date = May 2019 | pmid = 30821104 | doi = 10.1002/ajmg.a.61100 | s2cid = 73470267}}

Dermatosparaxis EDS (dEDS; formerly categorized as type 7C) is associated with extremely fragile skin leading to severe bruising and scarring; saggy, redundant skin, especially on the face; hypermobility ranging from mild to serious; and hernias. Variations in the ADAMTS2 gene cause it. It is extremely rare, with around 11 cases reported worldwide.{{cite web|url=https://rarediseases.info.nih.gov/diseases/2089/dermatosparaxis-ehlers-danlos-syndrome|title=Dermatosparaxis Ehlers–Danlos syndrome | work = Genetic and Rare Diseases Information Center (GARD) – an NCATS Program | publisher = U.S. National Institutes of Health |access-date=2019-06-03}}

Hypermobile EDS (hEDS, formerly categorized as type 3) is mainly characterized by hypermobility that affects both large and small joints. It may lead to frequent joint subluxations (partial dislocations) and dislocations. 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. It affects the skin less than other forms. It has no available genetic test. hEDS is the most common of the 19 types of connective tissue disorders. Since no genetic test exists, providers have to diagnose hEDS based on what they know about the condition and the patient's physical attributes. Other than the general signs, attributes can include faulty connective tissues throughout the body, musculoskeletal issues, and family history. Along with these general signs and side effects, patients can have trouble healing.{{cite web|url=https://www.ehlers-danlos.org/what-is-eds/information-on-eds/hypermobile-eds-and-hypermobility-spectrum-disorders/|title=Hypermobile EDS and Hypermobility Spectrum Disorders| vauthors = Carter K | work = Ehlers–Danlos Support UK}}

Pregnant individuals who have hEDS are at an increased risk for complications. 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. Individuals with hEDS may run the risk of falling, postpartum depression (more than the general population), and slow healing from the birthing process.{{cite web|url=https://www.ehlers-danlos.org/information/pregnancy-birth-feeding-and-hypermobile-ehlers-danlos-syndrome-hypermobility-spectrum-disorders/|title=Pregnancy, birth, feeding, and hypermobile Ehlers–Danlos syndrome/hypermobility spectrum disorders | work = The Ehlers–Danlos Support UK|access-date=2019-11-22}}

The Medical University of South Carolina discovered a gene variant common with hEDS patients.{{Cite web | vauthors = Cantu L | date = 14 July 2021 |title=MUSC researchers announce gene mutation discovery associated with EDS |url=https://web.musc.edu/about/news-center/2021/07/14/musc-researchers-announce-gene-mutation-discovery-associated-with-eds-ehlers-danlos |access-date=2023-02-08 | work = Medical University of South Carolina}}

While 12 of the 13 subtypes of EDS have genetic variations that can be tested for by genetic testing, there is no known genetic cause of hEDS. Recently, several labs and research initiatives have been attempting to uncover a potential hEDS gene. In 2018, the Ehlers–Danlos Society began the Hypermobile Ehlers–Danlos Genetic Evaluation (HEDGE) study.{{cite web |url=https://www.ehlers-danlos.com/hedge/|title=HEDGE Study| website= ehlers-danlos.com| publisher= | date= | access-date=}} The ongoing study has screened over 1,000 people who have been diagnosed with hEDS by the 2017 criteria to evaluate their genome for a common mutation. To date,{{When|date=March 2025}} 200 people with hEDS have had whole genome sequencing, and 500 have had whole exome sequencing; this study aims to increase those numbers significantly. {{cite web |url=https://www.ehlers-danlos.com/hedge/|title=HEDGE Study| website= ehlers-danlos.com| publisher= | date= | access-date=}}

Promising outcomes of this increased screening have been reported by the Norris Lab, led by Russell Norris, in the Department of Regenerative Medicine and Cell Biology at Medical University of South Carolina.{{cite web |url=https://www.thenorrislab.com/home|title= About the Lab| publisher= Norris Lab, Medical University of South Carolina| date= | access-date=}} Using CRISPR Cas-9 mediated genome editing on mouse models of the disease, the lab has recently identified a "very strong candidate gene"{{cite journal | vauthors = Gensemer C, Burks R, Kautz S, Judge DP, Lavallee M, Norris RA | title = Hypermobile Ehlers–Danlos syndromes: Complex phenotypes, challenging diagnoses, and poorly understood causes | journal = Developmental Dynamics | volume = 250 | issue = 3 | pages = 318–344 | date = March 2021 | pmid = 32629534 | pmc = 7785693 | doi = 10.1002/dvdy.220}} 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. While this candidate gene has not been publicly identified, the Norris lab has conducted several studies involving small population genome sequencing and come up with a working list of possible hEDS genes. A mutation in COL3A1{{cite journal | vauthors = Narcisi P, Richards AJ, Ferguson SD, Pope FM | title = A family with Ehlers–Danlos syndrome type III/articular hypermobility syndrome has a glycine 637 to serine substitution in type III collagen | journal = Human Molecular Genetics | volume = 3 | issue = 9 | pages = 1617–1620 | date = September 1994 | pmid = 7833919 | doi = 10.1093/hmg/3.9.1617}} in a single family with autosomal dominant hEDS phenotype was found to cause reduced collagen secretion and an over-modification of collagen. In 35 families, copy number alterations in TPSAB1,{{cite journal | vauthors = Lyons JJ, Yu X, Hughes JD, Le QT, Jamil A, Bai Y, Ho N, Zhao M, Liu Y, O'Connell MP, Trivedi NN, Nelson C, DiMaggio T, Jones N, Matthews H, Lewis KL, Oler AJ, Carlson RJ, Arkwright PD, Hong C, Agama S, Wilson TM, Tucker S, Zhang Y, McElwee JJ, Pao M, Glover SC, Rothenberg ME, Hohman RJ, Stone KD, Caughey GH, Heller T, Metcalfe DD, Biesecker LG, Schwartz LB, Milner JD | title = Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number | journal = Nature Genetics | volume = 48 | issue = 12 | pages = 1564–1569 | date = December 2016 | pmid = 27749843 | pmc = 5397297 | doi = 10.1038/ng.3696}} 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. An unknown number of people diagnosed with hEDS may have a reduced Tenascin X,and/or mutations in the TNXB gene.Zweers, Manon C et al. “Haploinsufficiency of TNXB is associated with hypermobility type of Ehlers-Danlos syndrome.” American journal of human genetics vol. 73,1 (2003): 214-7. doi:10.1086/376564{{cite journal | vauthors = Kaufman CS, Butler MG | title = Mutation in TNXB gene causes moderate to severe Ehlers-Danlos syndrome | journal = World Journal of Medical Genetics | volume = 6 | issue = 2 | pages = 17–21 | date = May 2016 | pmid = 28344932 | pmc = 5363719 | doi = 10.5496/wjmg.v6.i2.17 | doi-access = free }}

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 extracellular matrix, resulting in loss of collagen. A lack of collagen here is 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.{{cite journal | vauthors = Moore K, Fulmer D, Guo L, Koren N, Glover J, Moore R, Gensemer C, Beck T, Morningstar J, Stairley R, Norris RA | title = PDGFRα: Expression and Function during Mitral Valve Morphogenesis | journal = Journal of Cardiovascular Development and Disease | volume = 8 | issue = 3 | date = March 2021 | page = 28 | pmid = 33805717 | doi = 10.3390/jcdd8030028 | pmc = 7999759 | doi-access = free}} 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.{{citation needed|date=September 2022}}

Kyphoscoliosis EDS (kEDS; formerly categorized as type 6) is associated with severe hypotonia at birth, delayed motor development, progressive scoliosis (present from birth), and scleral fragility. 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 a "marfanoid habitus" characterized by long, slender fingers (arachnodactyly), unusually long limbs, and a sunken chest (pectus excavatum) or protruding chest (pectus carinatum). It can be caused by variations in the gene PLOD1, or rarely, in the FKBP14 gene.{{cite web|url=https://rarediseases.info.nih.gov/diseases/2083/kyphoscoliotic-ehlers-danlos-syndrome|title=Kyphoscoliotic Ehlers–Danlos syndrome | work = Genetic and Rare Diseases Information Center (GARD) – an NCATS Program | publisher = U.S. National Institutes of Health |access-date=2019-06-03}}

Musculocontractural EDS (mcEDS) is characterized by congenital multiple contractures, characteristically adduction-flexion contractures and/or talipes equinovarus (clubfoot), characteristic craniofacial features, which are evident at birth or in early infancy, and skin features such as skin hyperextensibility, bruising, skin fragility with atrophic scars, and increased palmar wrinkling. It can be caused by variations in the CHST14 gene. Some other cases can be caused by variations in the DSE gene.{{cite web|url=https://www.ncbi.nlm.nih.gov/gtr/conditions/C1866294/|title=Ehlers–Danlos syndrome, musculocontractural type - Conditions – GTR – NCBI|website=www.ncbi.nlm.nih.gov|access-date=2019-09-22}}

As of 2021, 48 individuals have been reported to have mcEDS-CHST14, while 8 individuals have mcEDS-DSE.{{cite journal | vauthors = Nitahara-Kasahara Y, Mizumoto S, Inoue YU, Saka S, Posadas-Herrera G, Nakamura-Takahashi A, Takahashi Y, Hashimoto A, Konishi K, Miyata S, Masuda C, Matsumoto E, Maruoka Y, Yoshizawa T, Tanase T, Inoue T, Yamada S, Nomura Y, Takeda S, Watanabe A, Kosho T, Okada T | title = A new mouse model of Ehlers–Danlos syndrome generated using CRISPR/Cas9-mediated genomic editing | journal = Disease Models & Mechanisms | volume = 14 | issue = 12 | pages = dmm048963 | date = December 2021 | pmid = 34850861 | pmc = 8713987 | doi = 10.1242/dmm.048963 | doi-access = free}}

Bethlem myopathy 2, formally known as Myopathic EDS (mEDS), is characterized by three major criteria: congenital muscle hypotonia and/or muscle atrophy that improves with age, proximal joint contractures of the knee, hip, and elbow, and hypermobility of distal joints (ankles, wrists, feet, and hands). Four minor criteria may also contribute to a diagnosis of mEDS. This disorder can be inherited through either an autosomal dominant or an autosomal recessive pattern. Molecular testing must be completed to verify that mutations in the COL12A1 gene are present; if not, other collagen-type myopathies should be considered.

Periodontal EDS (pEDS) is an autosomal-dominant disorder characterized by four major criteria of severe and intractable periodontitis of early-onset (childhood or adolescence), lack of attached gingiva, pretibial plaques, and family history of a first-degree relative who meets clinical criteria. Eight minor criteria may also contribute to the diagnosis of pEDS. Molecular testing may reveal mutations in C1R or C1S genes affecting the C1r protein.

Spondylodysplastic EDS (spEDS) is characterized by short stature (progressive in childhood), muscle hypotonia (ranging from severe congenital to mild later-onset), and bowing of limbs. It can be caused by variations in both copies of the B4GALT7 gene. Other cases can be caused by variations in the B3GALT6 gene. People with variations in this gene can have kyphoscoliosis, tapered fingers, osteoporosis, aortic aneurysms, and problems with the lungs. Other cases can be caused by the SLC39A13 gene. Those with variations in this gene have protuberant eyes, wrinkled palms of the hands, tapering fingers, and distal joint hypermobility.{{cite web|url=https://rarediseases.info.nih.gov/diseases/9991/spondylodysplastic-ehlers-danlos-syndrome/cases/31481#4870|title=Spondylodysplastic Ehlers–Danlos syndrome | work = Genetic and Rare Diseases Information Center (GARD) – an NCATS Program | publisher = U.S. National Institutes of Health |access-date=2019-09-22|archive-date=2020-07-08|archive-url=https://web.archive.org/web/20200708114805/https://rarediseases.info.nih.gov/diseases/9991/spondylodysplastic-ehlers-danlos-syndrome/cases/31481#4870|url-status=dead}}

Vascular EDS (vEDS; formerly categorized as type 4) is identified by skin that is thin, translucent, extremely fragile, and bruises easily. It is also characterized by fragile blood vessels and organs that can easily rupture. Affected people are frequently short, and have thin scalp hair. It also has characteristic facial features, including large eyes, an undersized chin, sunken cheeks, a thin nose and lips, and ears without lobes.{{cite journal | vauthors = Eagleton MJ | title = Arterial complications of vascular Ehlers–Danlos syndrome | journal = Journal of Vascular Surgery | volume = 64 | issue = 6 | pages = 1869–1880 | date = December 2016 | pmid = 27687326 | doi = 10.1016/j.jvs.2016.06.120 | url = https://www.jvascsurg.org/article/S0741-5214(16)30876-X/fulltext | doi-access = free}} {{open access}} Joint hypermobility is present, but generally confined to the small joints (fingers, toes). Other common features include club foot, tendon and/or muscle rupture, acrogeria (premature aging of the skin of the hands and feet), early-onset varicose veins, pneumothorax (collapse of a lung), the recession of the gums, and a decreased amount of fat under the skin. It can be caused by the variations in the COL3A1 gene. Rarely, COL1A1 variations can also cause it.

This group of disorders affects connective tissues across the body, with symptoms most typically present in the joints, skin, and blood vessels. 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.{{cite news|title=What are the Ehlers–Danlos Syndromes?|url=https://www.ehlers-danlos.com/what-is-eds/|access-date=2021-02-16|website=The Ehlers Danlos Society}} Effects may range from mildly loose joints to life-threatening cardiovascular complications.{{cite web|title=Ehlers–Danlos syndrome|url=https://ghr.nlm.nih.gov/condition/ehlers-danlos-syndrome#genes|website=Genetic Home Reference|access-date=4 April 2018}} Due to the diversity of subtypes within the EDS family, symptoms may vary widely between individuals diagnosed with EDS.{{Cite web |title=Ehlers Danlos Syndromes |url=https://rarediseases.org/rare-diseases/ehlers-danlos-syndrome/ |access-date=2022-04-19 |website=NORD (National Organization for Rare Disorders)}}

Musculoskeletal symptoms include hyperflexible joints that are unstable and prone to sprain, dislocation, subluxation, and hyperextension. As a result of frequent tissue injury, there can be an early onset of advanced osteoarthritis,{{cite web|url=http://www.mayoclinic.com/health/ehlers-danlos-syndrome/DS00706/DSECTION=symptoms|title=Ehlers–Danlos Syndrome|work=Mayo Clinic|archive-url=https://web.archive.org/web/20120625105904/http://www.mayoclinic.com/health/ehlers-danlos-syndrome/DS00706/DSECTION=symptoms|archive-date=25 June 2012|url-status=live|access-date=25 May 2012}} chronic degenerative joint disease, swan-neck deformity of the fingers,{{cite journal | vauthors = Wei DH, Terrono AL | title = Superficialis Sling (Flexor Digitorum Superficialis Tenodesis) for Swan Neck Reconstruction | journal = The Journal of Hand Surgery | volume = 40 | issue = 10 | pages = 2068–2074 | date = October 2015 | pmid = 26328902 | doi = 10.1016/j.jhsa.2015.07.018}} and Boutonniere deformity of the fingers. Tendon and ligament laxity offer minuscule protection from tearing in muscles and tendons, but these problems still persist.{{cite web|url=http://www.ehlersdanlosnetwork.org/vascular.html|title=Vascular Type-EDS|work=Ehlers–Danlos Syndrome Network C.A.R.E.S. Inc.|archive-url=https://web.archive.org/web/20120604093447/http://www.ehlersdanlosnetwork.org/vascular.html|archive-date=2012-06-04|url-status=dead|access-date=2012-05-25}}

Deformities of the spine, such as scoliosis (curvature of the spine), kyphosis (a thoracic hump), tethered spinal cord syndrome, craniocervical instability (CCI), and atlantoaxial instability may also be present.{{cite journal | vauthors = Dordoni C, Ciaccio C, Venturini M, Calzavara-Pinton P, Ritelli M, Colombi M | title = Further delineation of FKBP14-related Ehlers–Danlos syndrome: A patient with early vascular complications and non-progressive kyphoscoliosis, and literature review | journal = American Journal of Medical Genetics. Part A | volume = 170 | issue = 8 | pages = 2031–2038 | date = August 2016 | pmid = 27149304 | doi = 10.1002/ajmg.a.37728 | s2cid = 43512125 | hdl = 11379/494257 | hdl-access = free}}{{cite journal | vauthors = Henderson FC, Austin C, Benzel E, Bolognese P, Ellenbogen R, Francomano CA, Ireton C, Klinge P, Koby M, Long D, Patel S, Singman EL, Voermans NC | title = Neurological and spinal manifestations of the Ehlers–Danlos syndromes | journal = American Journal of Medical Genetics. Part C, Seminars in Medical Genetics | volume = 175 | issue = 1 | pages = 195–211 | date = March 2017 | pmid = 28220607 | doi = 10.1002/ajmg.c.31549 | s2cid = 4438281 | author-link8 = Petra Klinge | doi-access = free}} Osteoporosis and osteopenia are also associated with EDS and symptomatic joint hypermobility.{{cite journal |vauthors=Carbone L, Tylavsky FA, Bush AJ, Koo W, Orwoll E, Cheng S |date=2000 |title=Bone density in Ehlers–Danlos syndrome |journal=Osteoporosis International |volume=11 |issue=5 |pages=388–392 |doi=10.1007/s001980070104 |pmid=10912839 |s2cid=441230}}{{cite journal |vauthors=Nijs J, Van Essche E, De Munck M, Dequeker J |date=July 2000 |title=Ultrasonographic, axial, and peripheral measurements in female patients with benign hypermobility syndrome |journal=Calcified Tissue International |volume=67 |issue=1 |pages=37–40 |doi=10.1007/s00223001093 |pmid=10908410 |s2cid=21083444}}

There can also be myalgia (muscle pain) and arthralgia (joint pain),{{cite journal | vauthors = Gedalia A, Press J, Klein M, Buskila D | title = Joint hypermobility and fibromyalgia in schoolchildren | journal = Annals of the Rheumatic Diseases | volume = 52 | issue = 7 | pages = 494–496 | date = July 1993 | pmid = 8346976 | pmc = 1005086 | doi = 10.1136/ard.52.7.494}} which may be severe and disabling. Trendelenburg's sign is often seen, which means that when standing on one leg, the pelvis drops on the other side.{{cite web|url=http://vimeo.com/35766706|title=CSF Ehlers Danlos Colloquium, Dr Jan Dommerholt| vauthors = Dommerholt J |publisher=Chiari & Syringomyelia Foundation|archive-url=https://web.archive.org/web/20130504131227/http://vimeo.com/35766706|archive-date=4 May 2013|url-status=live|access-date=10 June 2013|date=2012-01-27}} Osgood–Schlatter disease, a painful lump on the knee, is common as well.{{cite book|title=Orthopaedic pathology| vauthors = Vigorita VJ, Mintz D, Ghelman B |publisher=Lippincott Williams and Wilkins|year=2008|isbn=978-0781796705|edition=2nd|location=Philadelphia|pages=5–6}} In infants, walking can be delayed (beyond 18 months of age), and bottom-shuffling instead of crawling occurs.{{cite web|url=http://bestpractice.bmj.com/best-practice/monograph/570/diagnosis/step-by-step.html|title=Ehlers–Danlos syndrome - Diagnosis – Approach|date=13 December 2016|website=BMJ Best Practice|archive-url=https://web.archive.org/web/20100819145654/http://bestpractice.bmj.com/best-practice/monograph/570/diagnosis/step-by-step.html|archive-date=19 August 2010|url-status=live|access-date=18 August 2017}}

File:Ehlers-Danlos syndrome3.jpg|Individual with EDS showing hypermobile fingers, including the "swan-neck" malformation on the 2nd–5th digits, and a hypermobile thumb

File:Ehlers-Danlos thumb.jpg|Individual with EDS displaying hypermobile thumb

File:Ehlers-Danlos syndrome2.jpg|Individual with EDS displaying hypermobile metacarpophalangeal joints

File:Kyphoscoliosis of the back of person with kyphoscoliosis EDS.png|Kyphoscoliosis of the back of someone with kyphoscoliosis EDS

File:Arthrochalasia EDS.png|Severe joint hypermobility in a girl with EDS arthrochalasia type

File:H-EDS.png|Male, late adolescent, with hypermobile type

The weak connective tissue causes abnormal skin. This may present as stretchy or in other types simply be velvet soft. In all types, some increased fragility occurs, but the degree varies depending on the underlying subtype. The skin may tear and bruise easily, and may heal with abnormal atrophic scars; atrophic scars that look like cigarette paper are a sign seen including in those whose skin might appear otherwise normal. In some subtypes, though not the hypermobile subtype, redundant skin folds occur, especially on the eyelids. Redundant skin folds are areas of excess skin lying in folds.{{cite web|url=http://morphopedics.wikidot.com/ehlers-danlos-syndrome|title=Ehlers Danlos Syndrome – Morphopedics|website=morphopedics.wikidot.com|access-date=2018-06-15}}

Other skin symptoms include molluscoid pseudotumors,{{cite web|url=http://www.ehlersdanlosnetwork.org/classical.html|title=Classical Type-EDS|work=Ehlers–Danlos Syndrome Network C.A.R.E.S Inc.|archive-url=https://web.archive.org/web/20120530034615/http://www.ehlersdanlosnetwork.org/classical.html|archive-date=2012-05-30|url-status=dead|access-date=2012-05-25}} especially on pressure points, petechiae,{{cite book|url=https://books.google.com/books?id=gU4Lfsess6cC&pg=PA465|title=Portable Signs and Symptoms |date=2007|publisher=Lippincott Williams & Wilkins|isbn=9781582556796|page=465|archive-url=https://web.archive.org/web/20171105195522/https://books.google.com/books?id=gU4Lfsess6cC&pg=PA465|archive-date=2017-11-05|url-status=live}} subcutaneous spheroids, livedo reticularis; piezogenic papules are less common.{{cite web|url=https://www.dermnetnz.org/topics/piezogenic-papules|title=Piezogenic papules – DermNet New Zealand|website=www.dermnetnz.org|archive-url=https://web.archive.org/web/20161126001705/https://www.dermnetnz.org/topics/piezogenic-papules|archive-date=2016-11-26|url-status=live}} In vascular EDS, skin can also be thin and translucent. In dermatosparaxis EDS, the skin is extremely fragile and saggy.

File:Atrophic scar of Ehlers Danlos syndrome.jpg|Atrophic scar in a case of EDS

File:PMC3567970 1752-1947-7-35-1 (cropped).png|Translucent skin in vascular EDS

File:Ehlers-Danlos syndrome4.jpg|Individual with EDS displaying skin hyperelasticity

File:Piezogenic papules.jpg|Piezogenic papules on the heel of an individual with hypermobile EDS

File:Skinhyperelasticity-1.jpg|Skin hyperelasticity in the wrist

Although cardiovascular involvement depends significantly on the diagnosed subtype of EDS, a number of co-morbidities and symptoms are closely linked to the disorder as a whole. Some studies suggest that structural abnormalities are not the root cause of the vast majority of cardiac symptoms,{{cite journal | vauthors = Hertel A, Black WR, Malloy Walton L, Martin J, Jones J | title = Cardiovascular Symptoms, Dysautonomia, and Quality of Life in Adult and Pediatric Patients with Hypermobile Ehlers-Danlos Syndrome: A Brief Review | journal = Current Cardiology Reviews | volume = 20 | issue = 1 | pages = 75–81 | date = January 2024 | pmid = 38275067 | pmc = 11071672 | doi = 10.2174/011573403X271096231203164216 }} but rather, dysautonomia is the primary culprit. Associated symptoms can include but are not limited to palpitations, near-syncope and syncope, heat intolerance, and difficulty managing blood pressure and heart rate.{{cite journal | vauthors = De Wandele I, Rombaut L, Leybaert L, Van de Borne P, De Backer T, Malfait F, De Paepe A, Calders P | title = Dysautonomia and its underlying mechanisms in the hypermobility type of Ehlers-Danlos syndrome | journal = Seminars in Arthritis and Rheumatism | volume = 44 | issue = 1 | pages = 93–100 | date = August 2014 | pmid = 24507822 | doi = 10.1016/j.semarthrit.2013.12.006 }} One study published in 2013 showed that patients with EDS were more likely to also be diagnosed with postural orthostatic tachycardia syndrome, more commonly known as POTS.

Weak connective tissues in the heart can cause problems with valve structure and function as well. Mitral valve prolapse and regurgitation and aortic root dilation are found more commonly in EDS patients and others with similar connective tissue disorders.{{cite journal | vauthors = Rashed ER, Ruiz Maya T, Black J, Fettig V, Kadian-Dodov D, Olin JW, Mehta L, Gelb BD, Kontorovich AR | title = Cardiovascular manifestations of hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders | journal = Vascular Medicine | volume = 27 | issue = 3 | pages = 283–289 | date = June 2022 | pmid = 35000503 | pmc = 9677229 | doi = 10.1177/1358863X211067566 }} In some cases, EDS manifests within the vasculature as well. Major artery aneurisms and dissections are sometimes seen as a result of faulty structural integrity.

• Thoracic outlet syndrome{{cite journal | vauthors = Ericson WB, Wolman R | title = Orthopaedic management of the Ehlers–Danlos syndromes | journal = American Journal of Medical Genetics. Part C, Seminars in Medical Genetics | volume = 175 | issue = 1 | pages = 188–194 | date = March 2017 | pmid = 28192621 | doi = 10.1002/ajmg.c.31551 | s2cid = 4377720 | eissn = 1552-4876 | doi-access = free}} {{free access}}
• Arterial rupture
• Valvular heart disease, such as mitral valve prolapse, creates an increased risk for infective endocarditis during surgery. This may progress to a life-threatening degree.{{cite journal | vauthors = Levy HP | journal = GeneReviews | year = 1993 | pmid = 20301456 | url = https://www.ncbi.nlm.nih.gov/books/NBK1279/ | title = Hypermobile Ehlers–Danlos Syndrome | publisher = University of Washington, Seattle | veditors = Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K, Amemiya A}} Heart conduction abnormalities have been found in those with hypermobility form of EDS.{{cite journal | vauthors = Camerota F, Castori M, Celletti C, Colotto M, Amato S, Colella A, Curione M, Danese C | title = Heart rate, conduction and ultrasound abnormalities in adults with joint hypermobility syndrome/Ehlers–Danlos syndrome, hypermobility type | journal = Clinical Rheumatology | volume = 33 | issue = 7 | pages = 981–987 | date = July 2014 | pmid = 24752348 | doi = 10.1007/s10067-014-2618-y | s2cid = 32745869 | url = https://www.researchgate.net/publication/261771333}}
• Dilation or rupture (aneurysm) of ascending aorta{{cite book | vauthors = Wenstrup RJ, Hoechstetter LB | chapter = The Ehlers–Danlos Syndromes | pages = 131–149 | veditors = Allanson JE, Cassidy SB |title=Management of genetic syndromes |date=2001 |publisher=Wiley-Liss |location=New York |isbn=978-0-471-31286-4}}
• Cardiovascular autonomic dysfunction such as postural orthostatic tachycardia syndrome{{cite journal | vauthors = Grigoriou E, Boris JR, Dormans JP | title = Postural orthostatic tachycardia syndrome (POTS): association with Ehlers-Danlos syndrome and orthopaedic considerations | journal = Clinical Orthopaedics and Related Research | volume = 473 | issue = 2 | pages = 722–728 | date = February 2015 | pmid = 25156902 | pmc = 4294907 | doi = 10.1007/s11999-014-3898-x | eissn = 1528-1132 }}{{cite journal | vauthors = Hakim A, O'Callaghan C, De Wandele I, Stiles L, Pocinki A, Rowe P | title = Cardiovascular autonomic dysfunction in Ehlers-Danlos syndrome-Hypermobile type | journal = American Journal of Medical Genetics. Part C, Seminars in Medical Genetics | volume = 175 | issue = 1 | pages = 168–174 | date = March 2017 | pmid = 28160388 | doi = 10.1002/ajmg.c.31543 | s2cid = 4439857 | doi-access = free }} {{free access}}{{cite journal | vauthors = Ormiston CK, Padilla E, Van DT, Boone C, You S, Roberts AC, Hsiao A, Taub PR | title = May-Thurner syndrome in patients with postural orthostatic tachycardia syndrome and Ehlers-Danlos syndrome: a case series | journal = European Heart Journal. Case Reports | volume = 6 | issue = 4 | pages = ytac161 | date = April 2022 | pmid = 35620060 | pmc = 9131024 | doi = 10.1093/ehjcr/ytac161 }}
• Raynaud's phenomenon
• Varicose veins{{cite journal | vauthors = Raffetto JD, Khalil RA | title = Mechanisms of varicose vein formation: valve dysfunction and wall dilation | journal = Phlebology | volume = 23 | issue = 2 | pages = 85–98 | date = April 2008 | pmid = 18453484 | doi = 10.1258/phleb.2007.007027 | s2cid = 33320026 | url = https://www.vsiveins.com/wp-content/uploads/2016/08/BasicScience-Mechanisms-of-VV-Formation-Raffetto-J-Phlebology-2008.pdf}}
• Heart murmur
• Heart conduction abnormalities

Weakened connective tissues can lead to pelvic organ prolapse in female patients with Ehlers–Danlos syndrome.{{cite journal | vauthors = Blagowidow N | title = Obstetrics and gynecology in Ehlers–Danlos syndrome: A brief review and update | journal = American Journal of Medical Genetics. Part C, Seminars in Medical Genetics | volume = 187 | issue = 4 | pages = 593–598 | date = December 2021 | pmid = 34773390 | doi = 10.1002/ajmg.c.31945 | s2cid = 244076387}} Patients may also experience voiding difficulties, frequent urinary tract infections, and incontinence due to structural abnormalities.{{cite journal | vauthors = McIntosh LJ, Stanitski DF, Mallett VT, Frahm JD, Richardson DA, Evans MI | title = Ehlers–Danlos syndrome: relationship between joint hypermobility, urinary incontinence, and pelvic floor prolapse | journal = Gynecologic and Obstetric Investigation | volume = 41 | issue = 2 | pages = 135–139 | date = 1996 | pmid = 8838976 | doi = 10.1159/000292060}} Pelvic girdle pain is also frequently reported.{{cite journal | vauthors = Kciuk O, Li Q, Huszti E, McDermott CD | title = Pelvic floor symptoms in natal women with Ehlers–Danlos syndrome: an international survey study | journal = International Urogynecology Journal | volume = 34 | issue = 2 | pages = 473–483 | date = February 2023 | pmid = 35751670 | doi = 10.1007/s00192-022-05273-8 | s2cid = 250022004}}

Menorrhagia, dysmenorrhea, and dyspareunia are common symptoms associated with Ehlers–Danlos syndrome{{cite journal | vauthors = Hugon-Rodin J, Lebègue G, Becourt S, Hamonet C, Gompel A | title = Gynecologic symptoms and the influence on reproductive life in 386 women with hypermobility type ehlers-danlos syndrome: a cohort study | journal = Orphanet Journal of Rare Diseases | volume = 11 | issue = 1 | pages = 124 | date = September 2016 | pmid = 27619482 | pmc = 5020453 | doi = 10.1186/s13023-016-0511-2 | doi-access = free}} and are often mistaken for endometriosis. 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.{{cite journal | vauthors = Kumskova M, Flora GD, Staber J, Lentz SR, Chauhan AK | title = Characterization of bleeding symptoms in Ehlers–Danlos syndrome | journal = Journal of Thrombosis and Haemostasis | volume = 21 | issue = 7 | pages = 1824–1830 | date = July 2023 | pmid = 37179130 | doi = 10.1016/j.jtha.2023.04.004 | s2cid = 258203231}}

In cases of pregnancy, patients with Ehlers–Danlos syndrome are more likely to experience complications during parturition. 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.{{cite journal | vauthors = Pearce G, Bell L, Pezaro S, Reinhold E | title = Childbearing with Hypermobile Ehlers–Danlos Syndrome and Hypermobility Spectrum Disorders: A Large International Survey of Outcomes and Complications | journal = International Journal of Environmental Research and Public Health | volume = 20 | issue = 20 | pages = 6957 | date = October 2023 | pmid = 37887695 | pmc = 10606623 | doi = 10.3390/ijerph20206957 | doi-access = free}}

Research suggests a correlation between connective tissue disorders such as Ehlers–Danlos syndrome and both structural and functional problems within the gastrointestinal tract.{{cite journal | vauthors = Fikree A, Chelimsky G, Collins H, Kovacic K, Aziz Q | title = Gastrointestinal involvement in the Ehlers–Danlos syndromes | journal = American Journal of Medical Genetics. Part C, Seminars in Medical Genetics | volume = 175 | issue = 1 | pages = 181–187 | date = March 2017 | pmid = 28186368 | doi = 10.1002/ajmg.c.31546}}

High incidences of coexisting inflammatory disorders suggest a correlation between connective tissue disorders and the development of such aforementioned conditions. Inflammatory bowel diseases such as Crohn's disease, ulcerative colitis{{cite journal | vauthors = Adib N, Davies K, Grahame R, Woo P, Murray KJ | title = Joint hypermobility syndrome in childhood. A not so benign multisystem disorder? | journal = Rheumatology | volume = 44 | issue = 6 | pages = 744–750 | date = June 2005 | pmid = 15728418 | doi = 10.1093/rheumatology/keh557}} and celiac disease{{cite journal | vauthors = Danese C, Castori M, Celletti C, Amato S, Lo Russo C, Grammatico P, Camerota F | title = Screening for celiac disease in the joint hypermobility syndrome/Ehlers–Danlos syndrome hypermobility type | journal = American Journal of Medical Genetics. Part A | volume = 155A | issue = 9 | pages = 2314–2316 | date = September 2011 | pmid = 21815256 | doi = 10.1002/ajmg.a.34134 | s2cid = 205314742}} are more common in EDS patients when compared to control groups. Of note, patients who are already diagnosed with an inflammatory bowel disorder are not necessarily likely to develop symptoms of a connective tissue disorder, as the two have separate but not totally confounding etiologies.{{cite journal | vauthors = Laszkowska M, Roy A, Lebwohl B, Green PH, Sundelin HE, Ludvigsson JF | title = Nationwide population-based cohort study of celiac disease and risk of Ehlers–Danlos syndrome and joint hypermobility syndrome | journal = Digestive and Liver Disease | volume = 48 | issue = 9 | pages = 1030–1034 | date = September 2016 | pmid = 27321543 | doi = 10.1016/j.dld.2016.05.019}} Eosinophilic esophagitis, an inflammatory condition characterized by allergic-type reactions to various foods and chemicals and extensive esophageal remodeling, is eight times more likely in patients with connective tissue disorders when compared to patients without.{{cite journal | vauthors = Abonia JP, Wen T, Stucke EM, Grotjan T, Griffith MS, Kemme KA, Collins MH, Putnam PE, Franciosi JP, von Tiehl KF, Tinkle BT, Marsolo KA, Martin LJ, Ware SM, Rothenberg ME | title = High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders | journal = The Journal of Allergy and Clinical Immunology | volume = 132 | issue = 2 | pages = 378–386 | date = August 2013 | pmid = 23608731 | pmc = 3807809 | doi = 10.1016/j.jaci.2013.02.030}}

Functionally, small bowel dysmotility, delayed gastric emptying and delayed colonic transit are commonly related to EDS.{{cite journal | vauthors = Zarate N, Farmer AD, Grahame R, Mohammed SD, Knowles CH, Scott SM, Aziz Q | title = Unexplained gastrointestinal symptoms and joint hypermobility: is connective tissue the missing link? | journal = Neurogastroenterology and Motility | volume = 22 | issue = 3 | pages = 252–e78 | date = March 2010 | pmid = 19840271 | doi = 10.1111/j.1365-2982.2009.01421.x | s2cid = 11516253}}{{cite journal | vauthors = Menys A, Keszthelyi D, Fitzke H, Fikree A, Atkinson D, Aziz Q, Taylor SA | title = A magnetic resonance imaging study of gastric motor function in patients with dyspepsia associated with Ehlers–Danlos Syndrome-Hypermobility Type: A feasibility study | journal = Neurogastroenterology and Motility | volume = 29 | issue = 9 | date = September 2017 | pmid = 28568908 | doi = 10.1111/nmo.13090 | s2cid = 776971 | url = https://cris.maastrichtuniversity.nl/en/publications/e950bcd8-6e97-46d7-9f88-9681b5125293}} These changes in transit speeds within the gastrointestinal system can cause a host of symptoms, including but not limited to abdominal pain, bloating, nausea, reflux symptoms, vomiting, constipation, and diarrhea.{{cite journal | vauthors = Zeitoun JD, Lefèvre JH, de Parades V, Séjourné C, Sobhani I, Coffin B, Hamonet C | title = Functional digestive symptoms and quality of life in patients with Ehlers–Danlos syndromes: results of a national cohort study on 134 patients | journal = PLOS ONE | volume = 8 | issue = 11 | pages = e80321 | date = 2013-11-22 | pmid = 24278273 | pmc = 3838387 | doi = 10.1371/journal.pone.0080321 | bibcode = 2013PLoSO...880321Z | doi-access = free | veditors = Karhausen J}}

Some studies also suggest problems with the liver, which is in large part responsible for bilirubin conjugation. Although research in this area is sparse, patients with joint hypermobility were found to have higher rates of indirect hyperbilirubinemia than control groups.{{cite journal | vauthors = Çınar M, Çakar M, Öztürk K, Çetindağlı İ, Yılmaz S, Dinç A | title = Investigation of joint hypermobility in individuals with hyperbilirubinemia | journal = European Journal of Rheumatology | volume = 4 | issue = 1 | pages = 36–39 | date = March 2017 | pmid = 28293451 | pmc = 5335885 | doi = 10.5152/eurjrheum.2016.16051}}

Structurally, changes within the musculature in the intestine such as increased elastin, can lead to increased frequency of herniation. Laxity of the phreno-esophageal and gastro-hepatic ligaments can lead to hiatal hernia,{{cite journal | vauthors = Nelson AD, Mouchli MA, Valentin N, Deyle D, Pichurin P, Acosta A, Camilleri M | title = Ehlers Danlos syndrome and gastrointestinal manifestations: a 20-year experience at Mayo Clinic | journal = Neurogastroenterology and Motility | volume = 27 | issue = 11 | pages = 1657–1666 | date = November 2015 | pmid = 26376608 | doi = 10.1111/nmo.12665 | s2cid = 41431319}}{{cite journal | vauthors = Thwaites PA, Gibson PR, Burgell RE | title = Hypermobile Ehlers–Danlos syndrome and disorders of the gastrointestinal tract: What the gastroenterologist needs to know | journal = Journal of Gastroenterology and Hepatology | volume = 37 | issue = 9 | pages = 1693–1709 | date = September 2022 | pmid = 35750466 | pmc = 9544979 | doi = 10.1111/jgh.15927}} which in turn can lead to commonly reported symptoms such as acid reflux, abdominal pain, early satiety, and bloating. Internal organ prolapses and intestinal intussusceptions occur with greater frequency in patients with weakened connective tissues.{{cite journal | vauthors = Castori M, Morlino S, Pascolini G, Blundo C, Grammatico P | title = Gastrointestinal and nutritional issues in joint hypermobility syndrome/Ehlers–Danlos syndrome, hypermobility type | journal = American Journal of Medical Genetics. Part C, Seminars in Medical Genetics | volume = 169C | issue = 1 | pages = 54–75 | date = March 2015 | pmid = 25821092 | doi = 10.1002/ajmg.c.31431 | s2cid = 11773627}}

Although neurogastroenterological manifestations in connective tissue disorders are common, their root cause is not yet known. Splanchnic circulation, small fiber neuropathy and altered vascular compliance have all been named as potential contributors to gastrointestinal complaints,{{cite journal | vauthors = Mehr SE, Barbul A, Shibao CA | title = Gastrointestinal symptoms in postural tachycardia syndrome: a systematic review | journal = Clinical Autonomic Research | volume = 28 | issue = 4 | pages = 411–421 | date = August 2018 | pmid = 29549458 | pmc = 6314490 | doi = 10.1007/s10286-018-0519-x}} particularly for patients who have a known, comorbid autonomic condition.

Chronic headaches are common in patients with Ehlers–Danlos syndrome, whether related to dysautonomia,{{cite journal | vauthors = Gazit Y, Nahir AM, Grahame R, Jacob G | title = Dysautonomia in the joint hypermobility syndrome | journal = The American Journal of Medicine | volume = 115 | issue = 1 | pages = 33–40 | date = July 2003 | pmid = 12867232 | doi = 10.1016/S0002-9343(03)00235-3 }} temporomandibular joint dysfunction (TMD), muscle tension, or craniocervical instability. Ligaments in the neck are unable to heal properly, so the neck structure cannot support the skull, which can then sink into the brain stem, blocking the flow of cerebrospinal fluid, which in turn causes autonomic dysfunction.{{cite web |date=2015 |title=Indices of Cranio-vertebral Instability |url=http://www.csfinfo.org/research/csf-funded-research/csf-ehlers-danlos-syndrome-colloquium/indices-cranio-vertebral-instability/ |url-status=live |archive-url=https://web.archive.org/web/20160916222752/http://www.csfinfo.org/research/csf-funded-research/csf-ehlers-danlos-syndrome-colloquium/indices-cranio-vertebral-instability/ |archive-date=2016-09-16 |work=Funded Research |publisher=Chiari & Syringomyelia Foundation |vauthors=Henderson F}}

Arnold–Chiari malformation{{cite journal | vauthors = Castori M, Voermans NC | title = Neurological manifestations of Ehlers-Danlos syndrome(s): A review | journal = Iranian Journal of Neurology | volume = 13 | issue = 4 | pages = 190–208 | date = October 2014 | pmid = 25632331 | pmc = 4300794 }} is also more frequently found in patients with EDS because of the instability at the juncture between skull and spine. This causes herniation of the posterior fossa below the foramen magnum.{{cite journal | vauthors = Dyste GN, Menezes AH, VanGilder JC | title = Symptomatic Chiari malformations. An analysis of presentation, management, and long-term outcome | language = en-US | journal = Journal of Neurosurgery | volume = 71 | issue = 2 | pages = 159–168 | date = August 1989 | pmid = 2746341 | doi = 10.3171/jns.1989.71.2.0159 }} Increased pressure created by the malformation can lead to a flattened pituitary gland, hormone changes, sudden severe headaches, ataxia, and poor proprioception.{{cite journal | vauthors = Langridge B, Phillips E, Choi D | title = Chiari Malformation Type 1: A Systematic Review of Natural History and Conservative Management | journal = World Neurosurgery | volume = 104 | pages = 213–219 | date = August 2017 | pmid = 28435116 | doi = 10.1016/j.wneu.2017.04.082 | url = https://discovery.ucl.ac.uk/id/eprint/1555498/ }}

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.{{cite web |date=18 January 2015 |title=Ehlers–Danilo's Syndrome – The Role of Collagen in the Eye – Information |url=http://www.ehlersdanlos.ca/ehlers-danlos-syndrome-the-role-of-collagen-in-the-eye/ |archive-url=https://web.archive.org/web/20160404112931/http://www.ehlersdanlos.ca/ehlers-danlos-syndrome-the-role-of-collagen-in-the-eye/ |archive-date=4 April 2016 |access-date=2019-07-06 |work=The Canadian Ehlers Danlos Association |vauthors=William A}}

Otological complications may also occur. Hearing loss is common, both conductive and sensorineural, and is most often bilateral.{{cite journal | vauthors = Weir FW, Hatch JL, Muus JS, Wallace SA, Meyer TA | title = Audiologic Outcomes in Ehlers-Danlos Syndrome | journal = Otology & Neurotology | volume = 37 | issue = 6 | pages = 748–752 | date = July 2016 | pmid = 27253074 | doi = 10.1097/MAO.0000000000001082 | s2cid = 5286116 }} Otosclerosis and instability of the bones in the inner ear may also contribute to hearing loss.{{cite journal | vauthors = Miyajima C, Ishimoto S, Yamasoba T | title = Otosclerosis associated with Ehlers-Danlos syndrome: report of a case | journal = Acta Oto-Laryngologica. Supplementum | volume = 127 | issue = 559 | pages = 157–159 | date = December 2007 | pmid = 18340588 | doi = 10.1080/03655230701600418 | s2cid = 2517459 }}

• Hiatal hernia
• Gastroesophageal reflux{{cite journal | vauthors = Zeitoun JD, Lefèvre JH, de Parades V, Séjourné C, Sobhani I, Coffin B, Hamonet C | title = Functional digestive symptoms and quality of life in patients with Ehlers–Danlos syndromes: results of a national cohort study on 134 patients | journal = PLOS ONE | volume = 8 | issue = 11 | pages = e80321 | date = November 2013 | pmid = 24278273 | pmc = 3838387 | doi = 10.1371/journal.pone.0080321 | bibcode = 2013PLoSO...880321Z | eissn = 1932-6203 | doi-access = free}}
• Poor gastrointestinal motility{{cite web | vauthors = Brockway L |title= Gastrointestinal manifestations of Ehlers–Danlos syndrome (hypermobility type) |date=April 2016 | work = Ehlers–Danlos Support UK |url=https://www.ehlers-danlos.org/about-eds/medical-information/gastrointestinal/gastro-and-eds/ |url-status=dead |archive-url=https://web.archive.org/web/20161114082846/https://www.ehlers-danlos.org/about-eds/medical-information/gastrointestinal/gastro-and-eds/ |archive-date=2016-11-14}}
• Dysautonomia{{cite web |title=Ehlers–Danlos Syndrome |date=2012 |work=Underlying Causes of Dysautonomia |publisher=Dysautonomia International |url=http://www.dysautonomiainternational.org/page.php?ID=150 |url-status=live |archive-url=https://web.archive.org/web/20141218135316/http://www.dysautonomiainternational.org/page.php?ID=150 |archive-date=2014-12-18}}
• Gorlin's sign (touch tongue to nose){{cite journal | vauthors = Létourneau Y, Pérusse R, Buithieu H | title = Oral manifestations of Ehlers–Danlos syndrome | journal = Journal | volume = 67 | issue = 6 | pages = 330–334 | date = June 2001 | pmid = 11450296 | url = http://www.cda-adc.ca/jcda/vol-67/issue-6/330.html | url-status = live | archive-url = https://web.archive.org/web/20161215221438/http://www.cda-adc.ca/jcda/vol-67/issue-6/330.html | archive-date = 2016-12-15}}
• Anal prolapse
• Flat feet
• Tracheobronchomalacia / tracheal collapse
• Collapsed lung (spontaneous pneumothorax)
• Nerve disorders (carpal tunnel syndrome, acroparesthesia, neuropathy, including small fiber neuropathy){{cite web |url=http://www.answers.com/topic/ehlers-danlos-syndrome |title=Ehlers–Danlos syndrome: Definition from |publisher=Answers.com |access-date=2014-02-27 |url-status=live |archive-url=https://web.archive.org/web/20140306231457/http://www.answers.com/topic/ehlers-danlos-syndrome |archive-date=2014-03-06}}
• Insensitivity to local anesthetics{{cite web| vauthors = Arendt-Nielsen L |title=Patients Suffering from Ehlers Danlos Syndrome Type III Do Not Respond to Local Anesthetics|url=http://www.ehlers-danlos.org/what-is-eds/medical-information/9-medical-information/154-local-anaesthetics-and-eds|url-status=dead|archive-url=https://web.archive.org/web/20150405042818/http://www.ehlers-danlos.org/what-is-eds/medical-information/9-medical-information/154-local-anaesthetics-and-eds|archive-date=2015-04-05}}
• Dental problems including gum disease and enamel hypoplasia
• Platelet aggregation failure (platelets do not clump together properly){{MedlinePlusEncyclopedia|001468|Ehlers–Danlos syndrome}}
• Mast cell disorders (including mast cell activation syndrome and mastocytosis){{cite journal | vauthors = Seneviratne SL, Maitland A, Afrin L | title = Mast cell disorders in Ehlers–Danlos syndrome | journal = American Journal of Medical Genetics. Part C, Seminars in Medical Genetics | volume = 175 | issue = 1 | pages = 226–236 | date = March 2017 | pmid = 28261938 | doi = 10.1002/ajmg.c.31555 | s2cid = 4438476 | doi-access = free}}
• Pregnancy complications: increased pain, mild to moderate peripartum bleeding, cervical insufficiency, uterine tearing, or premature rupture of membranes{{cite journal | vauthors = Lind J, Wallenburg HC | title = Pregnancy and the Ehlers–Danlos syndrome: a retrospective study in a Dutch population | journal = Acta Obstetricia et Gynecologica Scandinavica | volume = 81 | issue = 4 | pages = 293–300 | date = April 2002 | pmid = 11952457 | doi = 10.1034/j.1600-0412.2002.810403.x | hdl = 1765/72381 | s2cid = 39943713 | url = http://repub.eur.nl/pub/72381 | doi-access = free| hdl-access = free }} {{free access}}
• Hearing loss may occur in some types{{cite web |title=Ehlers Danlos Syndromes |url=https://rarediseases.org/rare-diseases/ehlers-danlos-syndrome/ |website=NORD (National Organization for Rare Disorders) |access-date=11 November 2019}}
• There is some evidence that EDS may be associated with greater than expected frequencies of neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD) and other learning, communication and motor issues, including autism spectrum conditions and Tourette syndrome.{{cite journal |vauthors=Baeza-Velasco C |title=Neurodevelopmental atypisms in the context of joint hypermobility, hypermobility spectrum disorders, and Ehlers–Danlos syndromes |journal=American Journal of Medical Genetics. Part C, Seminars in Medical Genetics |volume=187 |issue=4 |pages=491–499 |date=2021 |pmid=34741402 |doi=10.1002/ajmg.c.31946 |s2cid=243801668 |doi-access=}}

File:PMC2856381 IJD-55-86-g002.png|Gorlin's sign in a case of EDS

File:A case of keratoglobus in a case of Brittle cornea syndrome.png|Keratoglobus in a case of EDS with brittle cornea syndrome

Because it is often undiagnosed or misdiagnosed in childhood, some instances of EDS have been mischaracterized as child abuse.{{cite news |work=The Press Enterprise |archive-url= https://web.archive.org/web/20090228100719/http://www.pe.com/localnews/inland/stories/PE_News_Local_D_abuse03.3d48364.html |url=http://www.pe.com/localnews/inland/stories/PE_News_Local_D_abuse03.3d48364.html |archive-date=February 28, 2009 |title=Redlands mother stung by untrue suspicions presses for accountability in child abuse inquiries |date=April 3, 2008 | vauthors = Santschi DR}} The pain may also be misdiagnosed as a behavior disorder or Munchausen by proxy.{{cite journal | vauthors = Chopra P, Tinkle B, Hamonet C, Brock I, Gompel A, Bulbena A, Francomano C | title = Pain management in the Ehlers–Danlos syndromes | journal = American Journal of Medical Genetics. Part C, Seminars in Medical Genetics | volume = 175 | issue = 1 | pages = 212–219 | date = March 2017 | pmid = 28186390 | doi = 10.1002/ajmg.c.31554 | s2cid = 4433630 | doi-access = free}}

The pain associated with EDS ranges from mild to debilitating.{{cite journal | vauthors = Chopra P, Tinkle B, Hamonet C, Brock I, Gompel A, Bulbena A, Francomano C | title = Pain management in the Ehlers–Danlos syndromes | journal = American Journal of Medical Genetics. Part C, Seminars in Medical Genetics | volume = 175 | issue = 1 | pages = 212–219 | date = March 2017 | pmid = 28186390 | doi = 10.1002/ajmg.c.31554 | s2cid = 4433630 | doi-access = free}} {{free access}}

File:JCI0112881.f2.jpg

Every type of EDS except the hypermobile type (which affects the vast majority of people with EDS) can be positively tied to specific genetic variation{{citation needed|date=June 2022}}.

Variations in these genes can cause EDS:

• Collagen primary structure and collagen processing: ADAMTS2, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2
• Collagen folding and collagen cross-linking: PLOD1, FKBP14
• Structure and function of myomatrix: TNXB, COL12A1
• Glycosaminoglycan biosynthesis: B4GALT7, B3GALT6, CHST14, DSE
• Complement pathway: C1R, C1S
• Intracellular processes: SLC39A13, ZNF469, PRDM5

Variations in these genes usually alter the structure, production, or processing of collagen or proteins that interact with collagen. Collagen provides structure and strength to connective tissue. A defect in collagen can weaken connective tissue in the skin, bones, blood vessels, and organs, resulting in the features of the disorder. Inheritance patterns depend on the specific syndrome.

Most forms of EDS are inherited in an autosomal dominant pattern, which means only one of the two copies of the gene in question must be altered to cause a disorder. A few are inherited in an autosomal recessive pattern, which means both copies of the gene must be altered for a person to be affected. It can also be an individual (de novo or "sporadic") variation. Sporadic variations occur without any inheritance.{{Cite news|url=https://ehlers-danlos.com/eds-types/|title=EDS Types |work=The Ehlers Danlos Society|access-date=2017-05-22|archive-url=https://web.archive.org/web/20170624041438/https://ehlers-danlos.com/eds-types/|archive-date=2017-06-24|url-status=live}}

A diagnosis can be made by an evaluation of medical history and clinical observation. The Beighton criteria are widely used to assess the degree of joint hypermobility. DNA and biochemical studies can help identify affected people. Diagnostic tests include collagen gene-variant testing, collagen typing via skin biopsy, echocardiogram, and lysyl hydroxylase or oxidase activity, but these tests are not able to confirm all cases, especially in instances of an unmapped variation, so clinical evaluation remains important. If multiple members of a family are affected, prenatal diagnosis may be possible using a DNA information technique known as a linkage study.{{cite journal | vauthors = Sobey G | title = Ehlers–Danlos syndrome: how to diagnose and when to perform genetic tests | journal = Archives of Disease in Childhood | volume = 100 | issue = 1 | pages = 57–61 | date = January 2015 | pmid = 24994860 | doi = 10.1136/archdischild-2013-304822 | s2cid = 11660992 | url = http://adc.bmj.com/content/100/1/57 | doi-access = free}} {{free access}} Knowledge about EDS among all kinds of practitioners is poor.{{cite journal | vauthors = Ross J, Grahame R | title = Joint hypermobility syndrome | journal = BMJ | volume = 342 | pages = c7167 | date = January 2011 | pmid = 21252103 | doi = 10.1136/bmj.c7167 | s2cid = 1284069}}{{cite journal | vauthors = Castori M | title = Ehlers–danlos syndrome, hypermobility type: an underdiagnosed hereditary connective tissue disorder with mucocutaneous, articular, and systemic manifestations | journal = ISRN Dermatology | volume = 2012 | page = 751768 | year = 2012 | pmid = 23227356 | pmc = 3512326 | doi = 10.5402/2012/751768 | doi-access = free}} Research is ongoing to identify genetic markers for all types.{{Cite news|url=https://www.ehlers-danlos.com/eds-types/|title=The Types of EDS|work=The Ehlers Danlos Society|access-date=2018-10-17}}

Because no single gene has been identified as the sole cause of the most common type of EDS, hypermobile type, obtaining a diagnosis is often difficult.{{cite journal | vauthors = Forghani I | title = Updates in Clinical and Genetics Aspects of Hypermobile Ehlers Danlos Syndrome | journal = Balkan Medical Journal | volume = 36 | issue = 1 | pages = 12–16 | date = January 2019 | pmid = 30063214 | pmc = 6335943 | doi = 10.4274/balkanmedj.2018.1113 }} The 2017 diagnostic criteria are as follows:

• Criterion 1: Generalized joint hypermobility, as measured by the Beighton score
• Criterion 2: Minimum two of the following must be met:
• Symptoms that suggest a difference in connective tissue structure
• Unusually soft or velvety skin
• Mild skin hyperextensibility
• Unexplained striae distensae or rubae at the back, groins, thighs, breasts, and/or abdomen in adolescents, men, or pre-pubertal women without a history of significant gain or loss of body fat or weight
• Bilateral piezogenic papules of the heel
• Recurrent or multiple abdominal hernia(s)
• Atrophic scarring involving at least two sites and without the formation of truly papyraceous and/or hemosideric scars as seen in classical EDS
• Pelvic floor, rectal, and/or uterine prolapse in children, men, or nulliparous women without a history of morbid obesity or other known predisposing medical condition
• Dental crowding and high or narrow palate
• Arachnodactyly
• Arm span-to-height ratio ≥1.05
• Mitral valve prolapse (MVP) mild or greater based on strict echocardiographic criteria
• Aortic root dilatation with Z-score >+2
• Positive family history
• Proof that these symptoms interfere with daily life
• Musculoskeletal pain in two or more limbs, recurring daily for at least 3 months
• Chronic, widespread pain for ≥3 months
• Recurrent joint dislocations or frank joint instability, in the absence of trauma
• Criterion 3: Exclusion of all other possible connective tissue disorders that may be the root cause of symptoms.

In such cases where all criteria are met, a patient can be diagnosed with hEDS according to The International Consortium on Ehlers-Danlos Syndromes and Hypermobility Spectrum Disorders{{Cite web |title=The International Consortium on Ehlers-Danlos Syndromes and Hypermobility Spectrum Disorders - The Ehlers Danlos Society |url=https://www.ehlers-danlos.com/international-consortium/ |access-date=2024-10-21 |website=www.ehlers-danlos.com}}

Several disorders share some characteristics with EDS. For example, in cutis laxa, the skin is loose, hanging, and wrinkled. In EDS, the skin can be pulled away from the body, but is elastic and returns to normal when let go. In Marfan syndrome, the joints are very mobile, and similar cardiovascular complications occur. People with a "marfanoid" appearance are often tall and thin with long arms and legs and "spidery" fingers while EDS phenotypes vary considerably. Certain subtypes of EDS may involve short stature, large eyes, and the appearance of a small mouth and chin, due to a small palate. The palate can have a high arch, causing dental crowding. Blood vessels can sometimes be easily seen through translucent skin, especially on the chest. The genetic connective tissue disorder Loeys–Dietz syndrome also has symptoms that overlap with EDS.{{cite web|url=http://www.loeysdietz.org/en/medical-information/differential-diagnosis|title=Differential Diagnosis |website=www.loeysdietz.org|url-status=live|archive-url=https://web.archive.org/web/20170623074459/http://www.loeysdietz.org/en/medical-information/differential-diagnosis|archive-date=2017-06-23}}

In the past, Menkes disease, a copper metabolism disorder, was thought to be a form of EDS. People are commonly misdiagnosed with fibromyalgia, bleeding disorders, or other disorders that can mimic EDS symptoms. Because of these similar disorders and complications that can arise from an unmonitored case of EDS, a correct diagnosis is important.{{cite web |url=http://rarediseases.about.com/cs/ehlersdanlossynd/a/102603.htm |title=Ehlers–Danlos Syndrome |publisher=Rarediseases.about.com |date=2006-05-25 |access-date=2014-02-27 |url-status=live |archive-url=https://web.archive.org/web/20140412011912/http://rarediseases.about.com/cs/ehlersdanlossynd/a/102603.htm |archive-date=2014-04-12}} Pseudoxanthoma elasticum is worth consideration in diagnosis.{{cite web|url=https://ghr.nlm.nih.gov/condition/pseudoxanthoma-elasticum|title=Pseudoxanthoma elasticum |website=Genetics Home Reference|access-date=2018-04-17}}

No cure for Ehlers–Danlos syndrome is known, and treatment is supportive. Close monitoring of the cardiovascular system, physiotherapy, occupational therapy, and orthopedic instruments (e.g., wheelchairs, bracing, casting) may be helpful. This can help stabilize the joints and prevent injury. Orthopedic instruments are helpful for the prevention of further joint damage, especially for long distances. People should avoid activities that cause the joint to lock or overextend.{{cite web|url=https://www.ehlers-danlos.org/what-is-eds/information-on-eds/physiotherapy-and-self-management/|title=Physiotherapy and self-management – The Ehlers–Danlos Support UK|website=www.ehlers-danlos.org|access-date=2018-04-17}}

A physician may prescribe casting to stabilize joints. Physicians may refer a person to an orthotist for orthotic treatment (bracing). Physicians may also consult a physical and/or occupational therapist to help strengthen muscles and teach people how to properly use and preserve their joints.{{cite journal | vauthors = Rombaut L, Malfait F, De Wandele I, Cools A, Thijs Y, De Paepe A, Calders P | title = Medication, surgery, and physiotherapy among patients with the hypermobility type of Ehlers–Danlos syndrome | journal = Archives of Physical Medicine and Rehabilitation | volume = 92 | issue = 7 | pages = 1106–1112 | date = July 2011 | pmid = 21636074 | doi = 10.1016/j.apmr.2011.01.016 | url = https://www.academia.edu/20158514}}{{ cite journal |vauthors=Woerdeman LA, Ritt MJ, Meijer B, Maas M |url= https://www.academia.edu/24725432 |title= Wrist problems in patients with Ehlers–Danlos syndrome|journal=European Journal of Plastic Surgery |volume=23 |issue=4 |pages=208–210 |year=2000 | doi=10.1007/s002380050252|s2cid= 29979747}}

Aquatic therapy promotes muscular development and coordination.{{cite journal | vauthors = Callewaert B, Malfait F, Loeys B, De Paepe A | title = Ehlers–Danlos syndromes and Marfan syndrome | journal = Best Practice & Research. Clinical Rheumatology | volume = 22 | issue = 1 | pages = 165–189 | date = March 2008 | pmid = 18328988 | doi = 10.1016/j.berh.2007.12.005| url = https://biblio.ugent.be/publication/432358/file/6811097 }} With manual therapy, the joint is gently mobilized within the range of motion and/or manipulations. If conservative therapy is not helpful, surgical joint repair may be necessary. Medication to decrease pain or manage cardiac, digestive, or other related conditions may be prescribed. To decrease bruising and improve wound healing, some people have responded to vitamin C.{{EMedicine|article|943567|Genetics of Ehlers–Danlos Syndrome|treatment}} Medical care workers often take special precautions because of the sheer number of complications that tend to arise in people with EDS. In vascular EDS, signs of chest or abdominal pain are considered trauma situations.{{Cite news|url=https://www.ehlers-danlos.com/emergency/|title=Vascular (VEDS) Emergency Information |work=The Ehlers Danlos Society|access-date=2018-04-17}}

Cannabinoids and medical marijuana have shown some efficacy in reducing pain levels.{{Cite journal|url=https://tcapp.org/wp-content/uploads/2017/09/Pain-Management-in-Patients-with-Hypermobility-Syndrome.pdf|title=Topics in Pain Management: pain management in patients with hypermobility disorders: frequently missed causes of chronic pain|journal=Topics in Pain Management}}

In general, medical intervention is limited to symptomatic therapy. Before pregnancy, people with EDS may be recommended to have genetic counseling and to familiarize themselves with the risks pregnancy poses. Children with EDS should be given information about the disorder so they can understand why they should avoid contact sports and other physically stressful activities. Children should be taught that they should not demonstrate the unusual positions they can maintain due to loose joints, as this may cause early degeneration of the joints. Emotional support along with behavioral and psychological therapy can be useful. Support groups can be immensely helpful for people dealing with major lifestyle changes and poor health. Family members, teachers, and friends should be informed about EDS so they can accept and assist the child.{{Cite journal| vauthors = Giroux CM, Corkett JK, Carter LM |date=2016|title=The Academic and Psychosocial Impacts of Ehlers–Danlos Syndrome on Postsecondary Students: An Integrative Review of the Literature.|url=https://files.eric.ed.gov/fulltext/EJ1133767.pdf |journal=Journal of Postsecondary Education and Disability |volume=29|issue=4|page=414}}

Successful treatment of chronic pain in EDS requires a multidisciplinary team. The ways to manage pain can be to modify pain management techniques used in the normal population. Pain is classified into several types. One is nociceptive, which is caused by an injury sustained to tissues. Another is neuropathic pain, caused by abnormal signals by the nervous system. In many cases, the pain individuals experience is an unequal mix of the two. Physiotherapy (exercise rehabilitation) can be helpful, especially in stabilizing the core and the joints. Stretching exercises must be reduced to slow and gentle stretching to reduce the risks of dislocations or subluxations. Usable methods may include posture reeducation, muscle release, joint mobilization, trunk stabilization, and manual therapy for overworked muscles. Cognitive behavioural therapy is used in many chronic pain patients, especially those who have severe, chronic, life-controlling pain that is unresponsive to treatment. It has not been checked for efficiency in clinical trials. The state of pain management with EDS is considered insufficient.

Nonsteroidal anti-inflammatory drugs (NSAIDs) may help if the pain is caused by inflammation. However, long-term use of NSAIDs is often a risk factor for gastrointestinal, renal, and blood-related side effects. It can worsen symptoms of mast cell activation syndrome, a disease that may be associated with EDS. Acetaminophen can be used to avoid the bleeding-related side effects of NSAIDs.

Lidocaine can be applied topically after subluxations and painful gums. It can also be injected into painful areas in the case of musculoskeletal pain.

If the pain is neuropathic in origin, tricyclic antidepressants in low doses, anticonvulsants, and selective norepinephrine reuptake inhibitors can be used.

When a dislocation or subluxation does occur, muscle spasms and stress tend to occur, increasing pain and reducing the chances of the dislocation/subluxation naturally relieving. Methods to support a joint after such an incident include the usage of a sling to hold the joint in place and allow it to relax. Orthopedic casts are not advised as there could be pain if unrelaxed muscles are still trying to spasm out against the cast. Other solutions to promote relaxation are heat, gentle massaging, and mental distractions.{{Cite web |title=Dislocation/Subluxation Management |url=https://www.ehlers-danlos.com/dislocation-subluxation-management/ |access-date=2022-04-19 |website=The Ehlers Danlos Society}}

The instability of joints, leading to subluxations and joint pain, often requires surgical intervention in people with EDS. 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.

Common surgical procedures are joint debridement, tendon replacements, capsulorrhaphy, and arthroplasty. Aortic dissection and other such complications of vascular EDS will mandate surgical intervention. After surgery, the degree of stabilization, pain reduction, and people's satisfaction can improve, but surgery does not guarantee an optimal result; affected people and surgeons report being dissatisfied with the results. The consensus is that conservative treatment is more effective than surgery, particularly since people have extra risks of surgical complications due to the disease. Three basic surgical problems arise due to EDS – the strength of the tissues is decreased, which makes the tissue less suitable for surgery; the fragility of the blood vessels can cause problems during surgery; and wound healing is often delayed or incomplete. 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.{{cite journal | vauthors = Wiesmann T, Castori M, Malfait F, Wulf H | title = Recommendations for anesthesia and perioperative management in patients with Ehlers–Danlos syndrome(s) | journal = Orphanet Journal of Rare Diseases | volume = 9 | page = 109 | date = July 2014 | pmid = 25053156 | pmc = 4223622 | doi = 10.1186/s13023-014-0109-5 | doi-access = free}}

Local anesthetics, arterial catheters, and central venous catheters cause a higher risk of bruise formation in people with EDS. Some people with EDS also show a resistance to local anaesthetics.{{cite journal | vauthors = Parapia LA, Jackson C | s2cid = 7809153 | title = Ehlers–Danlos syndrome – a historical review | journal = British Journal of Haematology | volume = 141 | issue = 1 | pages = 32–35 | date = April 2008 | pmid = 18324963 | doi = 10.1111/j.1365-2141.2008.06994.x | doi-access = free}} {{free access}} Resistance to lidocaine and bupivacaine is not uncommon, and mepivacaine tends to work better in people with EDS. Special recommendations for anesthesia are given for people with EDS.{{Citation needed|date=February 2023}} Detailed recommendations for anesthesia and perioperative care of people with EDS should be used to improve safety.

Surgery in people with EDS requires careful tissue handling and a longer immobilization afterward.{{cite journal | vauthors = Shirley ED, Demaio M, Bodurtha J | title = Ehlers–danlos syndrome in orthopaedics: etiology, diagnosis, and treatment implications | journal = Sports Health | volume = 4 | issue = 5 | pages = 394–403 | date = September 2012 | pmid = 23016112 | pmc = 3435946 | doi = 10.1177/1941738112452385}}

The outcome for individuals with EDS depends on the specific type of EDS they have. Symptoms vary in severity, even in the same disorder, and the frequency of complications varies. Some people have negligible symptoms, while others are severely restricted in daily life. Extreme joint instability, chronic musculoskeletal pain, degenerative joint disease, frequent injuries, and spinal deformities may limit mobility. Severe spinal deformities may affect breathing. In the case of extreme joint instability, dislocations may result from simple tasks such as rolling over in bed or turning a doorknob. Secondary conditions such as autonomic dysfunction or cardiovascular problems, occurring in any type, can affect prognosis and quality of life. Severe mobility-related disability is seen more often in hEDS than in classical EDS or vascular EDS.{{cite news|url=https://www.ehlers-danlos.com/what-is-eds/|title=What are the Ehlers–Danlos Syndromes?|website=The Ehlers Danlos Society|access-date=2019-09-10}}

Although all types of EDS are potentially life-threatening, most people have a normal lifespan. 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. The median life expectancy in the population with vascular EDS is 48 years.{{cite journal | vauthors = Pepin M, Schwarze U, Superti-Furga A, Byers PH | title = Clinical and genetic features of Ehlers–Danlos syndrome type IV, the vascular type | journal = The New England Journal of Medicine | volume = 342 | issue = 10 | pages = 673–680 | date = March 2000 | pmid = 10706896 | doi = 10.1056/NEJM200003093421001 | citeseerx = 10.1.1.603.1293}} {{free access}}

• Pseudoaneurysm{{cite journal|vauthors=Pepin M, Schwarze U, Superti-Furga A, Byers PH|date=March 2000|title=Clinical and genetic features of Ehlers–Danlos syndrome type IV, the vascular type|journal=The New England Journal of Medicine|volume=342|issue=10|pages=673–680|doi=10.1056/NEJM200003093421001|pmid=10706896|doi-access=free}}
• Vascular lesions (nature is disputed) due to tears in the lining of the arteries or deterioration of congenitally thin and fragile tissue
• Enlarged arteries

• A 50% risk of colonic perforation exists in vascular Ehlers–Danlos syndrome.

• Pregnancy increases the likelihood of uterine rupture.
• Maternal mortality is around 12% for the vascular type.
• Uterine hemorrhage can occur during the postpartum recovery.

Ehlers–Danlos syndromes are estimated to occur in about one in 5,000 births worldwide. Initially, prevalence estimates ranged from one in 250,000 to 500,000 people, but these were soon found to be low, as medical professionals became more adept at diagnosis. EDS may be far more common than the currently accepted estimate due to the wide range of severities with which the disorder presents.{{cite web |url=http://www.medscape.com/viewarticle/466834_3 |title=Ehlers–Danlos Syndrome: Epidemiology |publisher=Medscape.com |access-date=2014-02-27 |url-status=live |archive-url=https://web.archive.org/web/20130424220037/http://www.medscape.com/viewarticle/466834_3 |archive-date=2013-04-24}}

The prevalence of the disorders differs dramatically. The most common is hypermobile EDS, followed by classical EDS. The others are very rare. For example, fewer than 10 infants and children with dermatosparaxis EDS have been described worldwide.

Some types of EDS are more common in Ashkenazi Jews. For example, the chance of being a carrier for dermatosparaxis EDS is one in 2,000 in the general population but one in 248 among Ashkenazi Jews.{{cite web|url=https://geneaware.clinical.bcm.edu/GeneAware/AboutGeneAware/DiseaseDetails.aspx?DiseaseID=335|title=Ehlers–Danlos syndrome type VIIc |website=geneaware.clinical.bcm.edu|archive-url=https://web.archive.org/web/20170814220911/https://geneaware.clinical.bcm.edu/GeneAware/AboutGeneAware/DiseaseDetails.aspx?DiseaseID=335|archive-date=2017-08-14|url-status=live|access-date=2017-07-24}}

Some recent studies have found that EDS is significantly more prevalent in people who identify as transgender or gender-diverse, or who suffer from gender dysphoria. 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.{{Cite journal|title=Gender dysphoria in adolescents with Ehlers–Danlos syndrome - PMC|date=2022 |pmc=9806399 |journal=Sage Open Medicine |volume=10 |doi=10.1177/20503121221146074 |pmid=36600979 | vauthors = Jones JT, Black WR, Moser CN, Rush ET, Malloy Walton L }} By comparison, roughly 1-2% of adolescents identify as trans or gender-diverse in the US overall.{{Cite web|url=https://williamsinstitute.law.ucla.edu/publications/trans-adults-united-states/|title=How Many Adults and Youth Identify as Transgender in the United States? |website=Williams Institute}} 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.https://f.oaes.cc/xmlpdf/e9629768-ba1a-4b51-8e32-b7f9c328de95/4858.pdf

Until 1997, the classification system for EDS included ten specific types and acknowledged that other rarer types existed. At this time, the classification system underwent an overhaul and was reduced to six major types using descriptive titles. Genetic specialists recognize that other types of this condition exist but have only been documented in single families. Except for hypermobility (type 3), the most common type of all ten types, some of the specific variations involved have been identified, and they can be precisely identified by genetic testing; this is valuable due to a great deal of variation in individual cases. Negative genetic test results do not rule out the diagnosis since not all variations have been discovered; therefore, the clinical presentation is crucial.{{cite web|url=http://www.ednf.org/what-eds|title=What is EDS | work = The Ehlers–Danlos National Foundation |access-date=2016-01-06|archive-url=https://web.archive.org/web/20160426150505/http://www.ednf.org/what-eds|archive-date=2016-04-26|url-status=dead}}

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. Inheritance patterns in this group include X-linked recessive, autosomal dominant, and autosomal recessive. Examples of types of related syndromes other than those above reported in the medical literature include:{{cite web|url=https://www.omim.org/search/?index=entry&start=1&limit=10&sort=score+desc,+prefix_sort+desc&search=ehlers-danlos+syndrome+|title = Ehlers–Danlos syndrome | work = Online Mendelian Inheritance in Man (OMIM) |access-date=2019-04-27}}

• {{OMIM|305200||none}}: type 5
• {{OMIM|130080||none}}: type 8 – unspecified gene, locus 12p13
• {{OMIM|225310||none}}: type 10 – unspecified gene, locus 2q34
• {{OMIM|608763||none}}: Beasley–Cohen type
• {{OMIM|130070||none}}: progeroid form – B4GALT7
• {{OMIM|130090||none}}: type unspecified
• {{OMIM|601776||none}}: D4ST1-deficient Ehlers–Danlos syndrome (adducted thumb-clubfoot syndrome) CHST14

EDS may have contributed to the virtuoso violinist Niccolò Paganini's skill, as he was able to play wider fingerings than a typical violinist.{{cite journal | vauthors = Yücel D | title = Was Paganini born with Ehlers–Danlos syndrome phenotype 4 or 3? | journal = Clinical Chemistry | volume = 41 | issue = 1 | pages = 124–125 | date = January 1995 | pmid = 7813066 | url = http://www.clinchem.org/cgi/pmidlookup?view=long&pmid=7813066 | doi = 10.1093/clinchem/41.1.124 | doi-access = free}} {{free access}}

Many sideshow performers have EDS. Several of them were billed as the Elastic Skin Man, the India Rubber Man, and Frog Boy. They included such well-known individuals (in their time) as Felix Wehrle, James Morris, and Avery Childs. Two performers with EDS currently hold world records. 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.{{cite web|url=https://www.guinnessworldrecords.com/world-records/72387-stretchiest-skin|title=Stretchiest skin|website=Guinness World Records|date=29 October 1999 |access-date=2019-06-22}}

File:Stevie Boebi & Annie Elainey.jpg

• Actress Cherylee Houston has hypermobile EDS. She uses a wheelchair and was the first full-time disabled actress on Coronation Street.{{cite web | vauthors = Rollo S |url=http://www.digitalspy.com/soaps/s3/coronation-street/news/a221287/houston-hits-out-at-preconceived-ideas.html |title=Houston hits out at 'preconceived ideas' – Coronation Street News – Soaps |website=Digital Spy |date=2010-05-22 |access-date=2014-02-27 |url-status=live |archive-url=https://web.archive.org/web/20130509105904/http://www.digitalspy.com/soaps/s3/coronation-street/news/a221287/houston-hits-out-at-preconceived-ideas.html |archive-date=2013-05-09}}
• Drag queen and winner of the 11th season of RuPaul's Drag Race Yvie Oddly{{Cite web | vauthors = Oddly Y |url= https://www.out.com/health/2019/4/11/drag-races-yvie-oddly-opens-about-living-ehlers-danos-disease|title=Drag Race's Yvie Oddly Opens Up About Living with Ehlers Danos Disease|date=April 11, 2019|website=www.out.com}}
• Eric the Actor, a regular caller to The Howard Stern Show{{cite magazine | vauthors = Rosenberg P |title=Eric the Actor: A Eulogy |url=https://www.rollingstone.com/culture/culture-news/howard-stern-regular-eric-the-actor-remembered-by-dj-peter-rosenberg-230579/ |magazine=Rolling Stone |access-date=23 July 2019 |date=30 September 2014}}
• Actress and activist Jameela Jamil{{cite web | vauthors = Gillespie C |title=Jameela Jamil Confirms She Has Ehlers–Danlos Syndrome |url=https://www.self.com/story/jameela-jamil-ehlers-danlos-syndrome |website=SELF |date=21 February 2019 |access-date=9 August 2019}}
• Writer and actress Lena Dunham{{Cite web |url= https://www.cnn.com/2019/11/03/entertainment/lena-dunham-ehlers-danlos-trnd/index.html |title=Lena Dunham goes on Instagram to reveal she has Ehlers–Danlos syndrome| vauthors = Ellis R |date=November 3, 2019|website=CNN}}
• Australian singer Sia{{cite web|url=https://www.newsweek.com/sia-ehlers-danlos-syndrome-1463391|title=Ehlers–Danlos syndrome: Singer Sia's condition explained| vauthors = Doherty J |date=2019-10-05|website=Newsweek|access-date=2019-11-11}}
• Singer Halsey{{cite web | vauthors = Palowski A |title=What is Ehlers–Danlos syndrome? Halsey reveals diagnosis |url=https://www.today.com/health/womens-health/ehlers-danlos-syndrome-rcna28215 |website=Today |date=11 May 2022 |access-date=19 September 2022}}
• YouTuber and disability rights activist Annie Elainey{{cite web | vauthors = Kienapple B |url=https://www.brit.co/youtuber-annie-elainey-profile/|title=Here's What YouTuber Annie Elainey Wants You to Know About Being Disabled|date=2017-09-01|website=Brit + Co|access-date=2019-11-11}}
• Miss America 2020 Camille Schrier{{cite web | vauthors = Bagalawis E |url= https://blogs.vcu.edu/pharmacy/2019/07/living-with-little-known-disorder-ehlers-danlos-sparked-miss-virginias-love-of-science/|title=Living with little-known disorder Ehlers–Danlos sparked Miss Virginia's love of science|website=VCU School of Pharmacy News|date=22 July 2019 |access-date=2020-03-01}}
• Baroque flautist, musicologist and broadcast classical music presenter Hannah French{{cite web |url= https://www.bbc.co.uk/programmes/profiles/34Fg2XVC3GXDtFyWRmPpNbW/hannah-french |title=Hannah French|work=Radio 3 Breakfast|publisher=BBC|accessdate=2023-12-25}}
• Deaf singer/songwriter Mandy Harvey
• YouTuber and disability rights activist Jessica Kellgren-Fozard{{Cite news |title=The Ehlers-Danlos Society Awards |url=https://www.ehlers-danlos.com/awards/ |access-date=2024-05-09 |website=The Ehlers Danlos Society |language=en-GB}}
• Singer-songwriter, author and artist Martha Marlow{{cite web | vauthors = Skelly S |url= https://www.smh.com.au/culture/music/she-made-us-cry-with-that-qantas-song-now-she-reveals-her-own-pain-20210429-p57ndz.html|title=She made us cry with that Qantas song. Now she reveals her own pain|website=Sydney Morning Herald|date=7 May 2021 |access-date=2023-02-05}}
• Pornographic actor and writer Lorelei Lee{{cite web|url=https://www.instagram.com/p/CHbKwZbhwEb/ |title=Lorelei Lee's Instagram profile post: "If it seems here on IG like I'm always having another medical procedure that's because it seems that way in real life too. You all are…" |publisher=Instagram.com |date=2020-11-10 |accessdate=2022-03-03}}
• Reality show contestant Trevor Jones, dead from the vascular form of the disorder{{cite web | vauthors = Kubota S |url=https://www.today.com/popculture/former-millionaire-matchmaker-contestant-trevor-jones-dies-suddenly-t235037|title=Former 'Millionaire Matchmaker' contestant Trevor Jones dies suddenly|website=Today|date=20 October 2021 |access-date=2021-10-20}}
• Scrunchie creator Rommy Hunt Revson, dead from a ruptured aorta{{cite news | vauthors = Plokhii O |title=WRommy Hunt Revson, who popularized scrunchie, dies at 78 |url=https://www.washingtonpost.com/obituaries/2022/09/19/rommy-hunt-revson-scrunchie-dead/ |newspaper=Washington Post |date=19 September 2022 |access-date=19 September 2022}}
• Japanese voice actress and singer Tomori Kusunoki{{cite web | url=https://www.oricon.co.jp/news/2255414/ | title=楠木ともり「エーラス・ダンロス症候群」と公表 『ニジガク』優木せつ菜役は降板 | trans-title = Tomori Kusunoki announces that she has Ehlers–Danlos syndrome, and quits her role as Setsuna Yuki in 'Nijigaku' | language = Japanese | date=November 2022 | work = Oricon News}}
• Chaz Lucius, an American former professional ice hockey player{{cite web |last1=Canadian Press |title=Jets' 2021 first-round pick Chaz Lucius retires due to medical reasons |url=https://www.tsn.ca/nhl/jets-2021-first-round-pick-chaz-lucius-retires-due-to-medical-reasons-1.2285436 |website=TSN |access-date=10 April 2025}}

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. When asked about this connection Rebecca Yarros agrees with the connection but says EDS goes unnamed due to the level of medical knowledge present in her story's world. Yarros has EDS and included it as a representation of her condition.{{cite web | vauthors = Straetker R | date = 9 August 2023 |title=What Condition Does Violet Have in Fourth Wing? Rebecca Yarros Reveals Answer |url=https://www.health.com/rebecca-yarros-fourth-wing-interview-7569752 |website=Health}}

Grey's Anatomy, a long-running TV series, approached the topic of EDS in their 13th season. In the episode "Falling Slowly", the show's doctors are confronted with confusion when met with diagnosing a patient. Due to complex and contradicting symptoms presented by the patient, the show's doctors ultimately give the diagnosis of EDS. This episode was based on conversations held by producers who talked with a patient and doctor who have EDS.{{cite web |title=Ehlers–Danlos syndrome (EDS) on Grey's Anatomy! |url=https://edswellness.org/ehlers-danlos-syndrome-eds-greys-anatomy/ |publisher=EDS Wellness |date=14 October 2016}}

Ehlers–Danlos–like syndromes are hereditary in Himalayan cats, some domestic shorthair cats,{{cite journal | vauthors = Scott DV | title = Cutaneous asthenia in a cat, resembling Ehlers–Danlos syndrome in man | journal = Veterinary Medicine, Small Animal Clinician | volume = 69 | issue = 10 | pages = 1256–1258 | date = October 1974 | pmid = 4496767 | doi = 10.3906/vet-1203-64 | doi-access = free}} and certain breeds of cattle.{{cite book | vauthors = Scott DW |date= 2008 |chapter-url= https://archive.org/details/ColorAtlasOfFarmAnimalDermatology/page/n49 |title= Color Atlas of Farm Animal Dermatology |publisher= Wiley Online Library|page= 61 |chapter= Congenital and hereditary skin diseases |doi= 10.1002/9780470344460 |isbn= 9780470344460}} It is seen as a sporadic condition in domestic dogs, with higher frequency in English Springers.{{cite web |title=English Springer Spaniel - Ehlers–Danlos Syndrome (Cutaneous Asthenia) |url=https://www.ufaw.org.uk/dogs/english-springer-spaniel----ehlers-danlos-syndrome-cutaneous-asthenia |website=Universities Federation for Animal Welfare |access-date=28 October 2023}} It has a similar treatment and prognosis. Animals with the condition should not be bred, as the condition can be inherited.{{cite web | vauthors = Grant D | date =

1 October 2016 |url=https://veterinary-practice.com/article/ehler-danlos-syndrome-cutaneous-asthenia-dermatosparaxis|title=Ehler–Danlos Syndrome (Cutaneous asthenia, dermatosparaxis)|website=veterinary-practice.com |access-date=2019-06-03}}

File:Ehlers-Danlos syndrome 2.jpg|EDS in a dog

File:Ehlers-Danlos Syndrome 1.jpg|Same dog with EDS

File:Ehlers-Danlos syndrome 3.jpg|EDS in the same dog showing an atrophic scar

Degenerative suspensory ligament desmitis is a similar condition seen in many breeds of horses.{{cite book | vauthors = Halper J | title = Progress in Heritable Soft Connective Tissue Diseases | chapter = Connective Tissue Disorders in Domestic Animals | series = Advances in Experimental Medicine and Biology | volume = 802 | pages = 231–240 | date = 2014 | pmid = 24443030 | doi = 10.1007/978-94-007-7893-1_14 | chapter-url = https://www.academia.edu/27480767 | isbn = 978-94-007-7892-4}} It was originally notated in the Peruvian Paso and thought to be a condition of overwork and older age, but it is being recognized in all age groups and all activity levels. It has been noted in newborn foals.

{{Portal|Medicine}}

• Hypermobility spectrum disorder

{{reflist}}

{{Commons category|Ehlers-Danlos syndrome}}

• {{Cite web | vauthors = Cueto I |date=2022-12-12 |title=Revenge of the gaslit patients: Now, as scientists, they're tackling Ehlers–Danlos syndromes |url=https://www.statnews.com/2022/12/12/ehlers-danlos-syndrome-patients-turned-researchers/ |access-date=2022-12-13 |website=STAT}}
• {{cite news |url=https://www.washingtonpost.com/dc-md-va/2021/12/27/ehlers-danlos-syndrome-alissa-zingman-treatment/ |title=A doctor struggled with a rare, incurable syndrome. Now she helps others overcome it. | vauthors = Wan W |date=December 27, 2021 |newspaper=The Washington Post}}
• [https://www.ehlers-danlos.com/ The Ehlers-Danlos Society]

{{Medical resources

| ICD10 = {{ICD10|Q|79|6|q|65}} (ILDS Q82.817)

| ICD9 = {{ICD9|756.83}}

| OMIM =

| DiseasesDB = 4131

| MedlinePlus = 001468

| eMedicineSubj = derm

| eMedicineTopic = 696

| eMedicine_mult = {{eMedicine2|ped|654}}

| MeshID = D004535

| Orphanet = 98249

| GeneReviewsNBK = NBK1244

| GeneReviewsName = Ehlers–Danlos Syndrome, Classic Type

| GeneReviewsNBK2 = NBK1494

| GeneReviewsName2 = Vascular Ehlers–Danlos Syndrome

| GeneReviewsNBK3 = NBK1279

| GeneReviewsName3 = Ehlers–Danlos Syndrome, Hypermobility Type

| GeneReviewsNBK4 = NBK1462

| GeneReviewsName4 = Ehlers–Danlos Syndrome, Kyphoscoliotic Form

|ICD10CM={{ICD10CM|Q79.6}}|ICD11={{ICD11|LD28.1}}}}

{{Collagen disease}}

{{Posttranslational modification disorders}}

{{Congenital malformations and deformations of integument}}

{{DEFAULTSORT:Ehlers-Danlos syndrome}}

Category:Abnormalities of dermal fibrous and elastic tissue

Category:Collagen disease

Category:Congenital disorders

Category:Connective tissue diseases

Category:Contortion

Category:Disorders of fascia

Category:Wikipedia medicine articles ready to translate

Category:Syndromes in mammals

Category:Syndromes with ADHD