Ehlers-Danlos SyndromeS (EDS) and Hypermobility Spectrum DIsorders:
Research, Resources, and Real-World Impact
This page is a living library of medical research focused on the Ehlers-Danlos syndromes and related connective tissue disorders. It exists for patients, caregivers, clinicians, and advocates who want to go deeper than surface-level explanations and access the science that shapes real lives.
Here, you’ll find articles, posts, peer-reviewed medical journals and studies organized by topic, including (but not limited to) women’s health, men’s health, pregnancy and OB-GYN considerations, gastrointestinal involvement, autonomic dysfunction, surgical outcomes, and emerging research such as GLP-1 medications and their implications for people living with hypermobility and EDS.
EDS does not present the same way in every body, and research is often scattered, outdated, or difficult to access. This page brings that information together in one place, with the goal of making evidence-based knowledge easier to find, easier to share, and easier to use when advocating for informed, compassionate care.
Knowledge is power.
It’s important to note as the medical /healthcare landscape changes and continues to develop, information may change, become outdated, or no longer be relevant. Please always trust the guidance of a trusted and knowledgeable healthcare provider over what you may read on the internet.
Diagnosing Ehlers Danlos Syndromes (EDS)
and/or Hypermobility Spectrum Disorders (HSD)
There’s no one set of diagnostic criteria for the Ehlers Danlos Syndromes. Each type has its own set of criteria and clinical features.
For all EDS types except hEDS (hypermobile Ehlers Danlos),
diagnosis requires genetic confirmation, after clinical suspicion based on meeting the clinical characteristics.
Let’s dive into each type and the diagnostic criteria for each.
(the following diagnostic criteria has been sourced from: hsa, ehlers-danlos.com, and edsuk, and johnshopkins)
Arthochalasia EDS (aEDS)
- A patient must have one of the following: Skin hyperextensibility, Congenital bilateral hip dislocation, or Severe generalized joint hypermobility, with multiple dislocations/subluxations
- And at least two of the following: Muscle hypotonia, Kyphoscoliosis, Radiologically mild osteopenia, Tissue fragility, including atrophic scars, Easily bruisable skin
- Diagnosis can be confirmed with genetic testing. (COL1A1 or COL1A2)
Brittle Cornea Syndrome
- A patient with Brittle Cornea Syndrome will present with:
- Thin cornea (central corneal thickness often <400µm) and one of the following:
- Early onset progressive keratoconus
- Early onset progressive keratoglobus
- Blue sclerae
- Thin cornea (central corneal thickness often <400µm) and one of the following:
- OR with:
- Thin cornea
- And at least three of the following:
- Enucleation or corneal scarring as a result of previous rupture
- Progressive loss of corneal stromal depth, especially in central cornea
- High myopia, with normal or moderately increased axial length
- Retinal detachment
- Deafness, often with mixed conductive and sensorineural components, progressive, higher frequencies often more severely affected (“sloping” pure tone audiogram)
- Hypercompliant tympanic membranes
- Developmental dysplasia of the hip
- Hypotonia in infancy, usually mild if present
- Scoliosis
- Arachnodactyly
- Hypermobility of distal joints
- Pes planus, hallux valgus
- Mild contractures of fingers
- Soft, velvety skin, translucent skin
- Genetic testing for pathogenic variants of the following genes is needed to confirm diagnosis if a patient meets the criteria above:
- ZNF469 or
- PRDM5
Classical EDS (cEDS)
- For Classic EDS, the criteria can be met in two different ways. A patient must have two from Group A; or one from Group A and three or more from Group B.
- Group A: Skin hyperextensibility and atrophic scarring, Generalized joint hypermobility
- Group B: Easy bruising, Soft, doughy skin, Skin fragility (or traumatic splitting), Molluscoid pseudotumors, Subcutaneous spheroids, Hernia (or history thereof), Epicanthal folds, Complications of joint hypermobility (e.g., sprains, dislocations/subluxations, pain, flexible flatfoot), Family history of a first-degree relative who meets clinical criteria
- Genetic testing can confirm diagnosis: COL5A1 or COL5A2 genes; in rarer cases, some pateints who meet the above criteria but do not showtha variants with the aforementioned genes, may show variations at the COL1A1 gene, instead.
Classical-Like EDS (clEDS)
- A patient must have all three: Skin hyperextensibility, with velvety skin texture and absence of atrophic scarring, Generalized joint hypermobility, with or without recurrent dislocations (most commonly shoulder and ankle), Easily bruisable skin/spontaneous ecchymoses
- May also have: Foot deformities (broad/plump forefoot; brachydactyly with excessive skin; pes planus; hallux valgus; piezogenic papules), Edema in the legs in the absence of cardiac failure, Mild proximal and distal muscle weakness, Axonal polyneuropathy, Atrophy of muscles in hands and feet, Acrogeric hands, mallet finger(s), clinodactyly, brachydactyly, Vaginal/uterus/rectal prolapse
- As well as MUST have family history of compatible with autosomal recessive inheritance of the TNXB gene and/ or AEBP1 gene (rare).
Cardiac-Valvular EDS (cvEDS)
- Diagnostic criteria for cvEDS is a bit more complex. A patient must have severe progressive cardiac-valvular problems (aortic valve, mitral valve) as well as family history compatible with autosomal recessive inheritance (COL1A2 gene) and one of the following:
- Skin involvement: skin hyperextensibility, atrophic scars, thin skin, easy bruising, Joint hypermobility (generalized or restricted to small joints)
- OR three of the following:
- Inguinal hernia, Pectus deformity (especially excavatum), Joint dislocations, Foot deformities: pes planus, pes planovalgus, hallux valgus
Dermatosparaxis EDS (dEDS)
- dEDS is diagnosed if a patient has Extreme skin fragility with congenital or postnatal skin tears, Characteristic craniofacial features, which are evident at birth or early infancy or evolve later in childhood, as well as one of the following from Group A or three or more from Group B
- Group A: Extreme skin fragility with congenital or postnatal skin tears, Characteristic craniofacial features, which are evident at birth or early infancy or evolve later in childhood, Redundant, almost lax skin, with excessive skin folds at the wrists and ankles, Increased palmar wrinkling, Severe bruisability with a risk of subcutaneous hematomas and hemorrhage, Umbilical hernia, Postnatal growth retardation, Short limbs, hands, and feet, Perinatal complications due to connective tissue fragility
- Group B: Soft and doughy skin texture, Skin hyperextensibility, Atrophic scars, Generalized joint hypermobility, Complications of visceral fragility (e.g., bladder rupture, diaphragmatic rupture, rectal prolapse), Delayed motor development, Osteopenia, Hirsutism, Tooth abnormalities, Refractive errors (myopia, astigmatism), Strabismus
Hypermobile EDS (hEDS)
- For hEDS, a patient must have all 3:
- Generalized joint hypermobility
- Two of the following:
- Positive family history
- Musculoskeletal complications (one of the following)
- for example, Musculoskeletal pain in two or more limbs, recurring daily for at least three (3) months; or Chronic, widespread pain for at least three (3) months; or Recurrent joint dislocations or frank joint instability, in the absence of trauma
- Manifestations of a conective tissue disorder (five or more of the following)
- Unusually soft or velvety skin
- Mild skin hyperextensibility
- Unexplained striae such as striae distensae or rubrae 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) (e.g., umbilical, inguinal, crural)
- Atrophic scarring involving at least two (2) 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, as defined in one or more of the following:
- positive wrist sign (Steinberg sign) on both sides
- positive thumb sign (Walker sign) on both sides
- 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
- And lastly, all of following:
- Absence of unusual skin fragility, which should prompt consideration of other types of EDS
- Exclusion of other heritable and acquired connective tissue disorders, including autoimmune rheumatologic conditions
- Exclusion of alternative diagnoses that may also include joint hypermobility by means of hypotonia and/or connective tissue laxity.
- Patients and Providers in need of a fillable checklist form (beighton score) please click here to download an editable doc.
- While younger patients may not be able to be diagnosed until they’re older, please review this framework to be used in pediatric settings. Click Here.
Hypermobility Spectrum Disorders
- Adults with HSD are diagnosed when symptomatic joint hypermobility can not be explained by any other condition. HSD is then divided nto 4 categories:
- Generalized HSD (joint hypermobility throughout body) G-HSD
- Peripheral HSD (joint hypermobility throughout throughout hands and feet) P-HSD
- Localized HSD (joint hypermobility in a single joint or group of jionts in a localized area) L-HSD
- Historical HSD (history of generalized joint hypermobility throughout whole body; may not be current hypermobility) H-HSD
- Children with HSD are diagnosed differently. The 2023 framework for diagnosis can be found here, on the The EDS Society website.
Kyphoscoliotic EDS (kEDS)
- Most often, a patient with kEDS will present with all three of the following:
- Congenital muscle hypotonia
- Congenital or early onset kyphoscoliosis (progressive or non-progressive)
- Generalized joint hypermobility with dislocations/subluxations (shoulders, hips, and knees in particular)
- Alternatively, patients presenting with the following may also be diagnosed with kEDS:
- Congenital muscle hypotonia AND Congenital or early onset kyphoscoliosis (progressive or non-progressive)
- As well as, three of the following (or three of the gene specific characteristics):
- Skin hyperextensibility
- Easily bruisable skin
- Rupture/aneurysm of a medium-sized artery
- Osteopenia/osteoporosis
- Blue sclerae
- Hernia (umbilical or inguinal)
- Pectus deformity
- Marfanoid habitus
- Talipes equinovarus
- Refractive errors (myopia, hypermetropia)
- The genes associated with kEDS, are PLOD1 and FKBP14
- PLOD1 – most common characteristics with variants to this gene include:
- Skin fragility (easy bruising, friable skin, poor wound healing, widened atrophic scarring)
- Scleral and ocular fragility/rupture
- Microcornea
- Facial dysmorphology
- FKBP14 – most common characteristics with variants to this gene include:
- Congenital hearing impairment (sensorineural, conductive, or mixed)
- Follicular hyperkeratosis
- Muscle atrophy
- Bladder diverticula
- PLOD1 – most common characteristics with variants to this gene include:
Musculocontractural EDS (mcEDS)
- For a patient at birth (or in toddler years- early childhood) to be diagnosed with mcEDS, they must have:
- Congenital multiple contractures, characteristically adduction-flexion contractures and/or talipes equinovarus (clubfoot)
- Characteristic craniofacial features, which are evident at birth or in early infancy
- For a patient in adolesence or adulthood, they must have:
- Congenital multiple contractures, characteristically adduction-flexion contractures and/or talipes equinovarus (clubfoot)
- Characteristic cutaneous features including skin hyperextensibility, easy bruisability, skin fragility with atrophic scars, increased palmar wrinkling
- The following is a list of common characteristics that can be present at any age with mcEDS but do not confirm diagnosis:
- Recurrent/chronic dislocations
- Pectus deformities (flat, excavated)
- Spinal deformities (scoliosis, kyphoscoliosis)
- Peculiar fingers (tapering, slender, cylindrical)
- Progressive talipes deformities (valgus, planus, cavum)
- Large subcutaneous hematomas
- Chronic constipation
- Colonic diverticula
- Pneumothorax/ pneumohemothorax
- Nephrolithiasis/cystolithiasis
- Hydronephrosis
- Cryptorchidism in males
- Strabismus
- Refractive errors (myopia, astigmatism)
- Glaucoma/elevated intraocular pressure
- Genetic testing (for variants in the CHST14 gene) and meeting clinical criteria are the only way to confirm a mcEDS diagnosis.
Myopathic EDS (mEDS)
- A patient with mEDS will present with either:
- Congenital muscle hypotonia and/or muscle atrophy that improves with age , and either *Proximal joint contractures (knee, hip, and elbow) or *Hypermobility of distal joints
- OR
- Congenital muscle hypotonia and/or muscle atrophy that improves with age and three of the following:
- Soft, doughy skin
- Atrophic scarring
- Motor developmental delay
- Myopathy on muscle biopsy
- Genetic counseling will confirm diagnosis. It’s not definitive which gene is most responsible for mEDS, but variants in the CYP2C19 gene are most likely responsible according tot he science available at this time.
Periodontal EDS (pEDS)
- For pEDS, a patient must have one of the following sets of qualifers frmo either Group A or Group B.
- Group A:
- Severe and intractable periodontitis of early onset (childhood or adolescence)
- Two of the following:
- Lack of attached gingiva
- Pretibial plaques
- Family history of a first-degree relative who meets the clinical diagnostic criteria for pEDS
- And one of the following:
- Easy bruising
- Joint hypermobility, mostly distal joints
- Skin hyperextensibility and fragility, abnormal scarring (wide or atrophic)
- Increased rate of infections
- Hernias
- Marfanoid facial features
- Acrogeria
- Prominent vasculature
- Group B:
- Lack of attached gingiva
- Two of the following:
- Severe and intractable periodontitis of early onset (childhood or adolescence)
- Pretibial plaques
- Family history of a first-degree relative who meets the clinical diagnostic criteria for pEDS
- And one of the following:
- Easy bruising
- Joint hypermobility, mostly distal joints
- Skin hyperextensibility and fragility, abnormal scarring (wide or atrophic)
- Increased rate of infections
- Hernias
- Marfanoid facial features
- Acrogeria
- Prominent vasculature
- Group A:
- Confirmation of diagnosis is done by a geneticist who will test for pathagenic variants of the C1R or C1S genes.
Spondylodysplastic EDS (spEDS)
- A patient will present with spEDS if they have:
- Short stature (progressive in childhood)
- Muscle hypotonia (ranging from severe congenital to mild later onset)
- As well as”
- characteristic radiographic abnormalities
- and two of the following:
- Skin hyperextensibility, soft, doughy skin, thin, translucent skin
- Pes planus
- Delayed motor development
- Osteopenia
- Delayed cognitive development
- Or * two of the following gene (B4GALT7) specific:
- Radioulnar synostosis
- Bilateral elbow contractures or limited elbow movement
- Generalized joint hypermobility
- Single transverse palmar crease
- Characteristic craniofacial features
- Characteristic radiographic findings
- Severe hypermetropia
- Clouded cornea
- Or two of the following gene (B3GALT6) specific:
- Kyphoscoliosis (congenital or early onset, progressive)
- Joint hypermobility (generalized or restricted to distal joints, with joint dislocations)
- Joint contractures (congenital or progressive, especially hands)
- Peculiar fingers (slender, tapered, arachnodactyly, spatulate, with broad distal phalanges)
- Talipes equinovarus
- Characteristic craniofacial features
- Tooth discoloration, dysplastic teeth
- Characteristic radiographic findings
- Osteoporosis with multiple spontaneous fractures
- Ascending aortic aneurysm
- Lung hypoplasia, restrictive lung disease
- Or two fo the following gene (SLC39A13)specific:
- Protuberant eyes with bluish sclerae
- Hands with finely wrinkled palms
- Atrophy of the thenar muscles and tapering fingers
- Hypermobility of distal joints
- Characteristic radiologic findings
Vascular EDS (vEDS)
- For vEDS, a patient should pursue genetic testing if they have experienced any (one) of the following:
- Family history of vEDS with a documented causative variant in COL3A1
- Arterial rupture at a young age
- Spontaneous sigmoid colon perforation in the absence of known diverticular disease or other bowel pathology
- Uterine rupture during the third trimester in the absence of previous C-section and/or severe peripartum perineum tears
- Carotid-cavernous sinus fistula (CCSF) formation in the absence of trauma
- If a patient has experienced several of the fllowing, genetic testing is recommended:
- Bruising unrelated to identified trauma and/or in unusual sites such as the cheeks and back
- Thin, translucent skin with increased venous visibility
- Characteristic facial appearance
- Spontaneous pneumothorax
- Acrogeria
- Talipes equinovarus
- Congenital hip dislocation
- Hypermobility of small joints
- Tendon and muscle rupture
- Keratoconus
- Gingival recession and gingival fragility
- Early-onset varicose veins (under age 30 and starting before pregnancy if female)
This is a living resource.
This page is actively growing and will continue to evolve as new Ehlers-Danlos research is published, updated, and reviewed. Medical understanding changes, and this space will change with it. As I continue to read and review more studies, I will add links here.
Thank you for being here, and for caring about informed, evidence-based EDS and hypermobile care.
