All Informed Patient Project guides are grounded in peer-reviewed research and established clinical guidelines. Sources are listed by specialty guide below. Where a source is cited across multiple guides, it is listed in full in each relevant section for ease of provider reference.
Last reviewed: March 2026. This page is updated as new literature is incorporated into our guides. Sources reflect the evidence base at time of publication for each guide. For questions about specific citations,
contact us.
These sources inform the systemic overview, diagnostic criteria, hEDS trifecta framework, and general clinical guidance shared across both guides.
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1
Malfait F, Francomano C, Byers P, et al.
The 2017 international classification of the Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2017;175C:8–26.
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2
Tinkle B, Castori M, Berglund B, et al.
Hypermobile Ehlers-Danlos syndrome (a.k.a. Ehlers-Danlos syndrome Type III and Ehlers-Danlos syndrome hypermobility type): Clinical description and natural history.
American Journal of Medical Genetics Part C. 2017;175C:48–69.
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3
Daylor V, Griggs M, Weintraub A, et al.
Defining the chronic complexities of hEDS and HSD: A global survey of diagnostic challenges, life-long comorbidities, and unmet needs.
Journal of Clinical Medicine. 2025;14(16):5636.
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4
The Ehlers-Danlos Society.
Clinical resources, diagnostic criteria, and patient/provider education materials for hEDS and related conditions.
ehlers-danlos.com. Accessed 2025–2026.
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5
Fairweather D, Bruno KA, et al.
An overview of Ehlers-Danlos syndrome and the link between postural orthostatic tachycardia syndrome and gastrointestinal symptoms with a focus on gastroparesis.
Frontiers in Physiology. 2024. PMC11390471.
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6
Fikree A, Akbar A, Grahame R, Costigan C, Aziz Q.
The suggested relationships between common GI symptoms and joint hypermobility, POTS, and MCAS.
Gastro-Hep Communications. 2024. PMC11348541.
These sources inform GI manifestations of hEDS, MCAS and histamine intolerance, dysmotility, and the hEDS/POTS/MCAS trifecta as it presents in gastroenterology.
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1
Malfait F, Francomano C, Byers P, et al.
The 2017 international classification of the Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2017;175C:8–26.
-
2
Tinkle B, Castori M, Berglund B, et al.
Hypermobile Ehlers-Danlos syndrome: Clinical description and natural history.
American Journal of Medical Genetics Part C. 2017;175C:48–69.
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3
Castori M, Tinkle B, Levy H, Grahame R, Malfait F, Hakim A.
A framework for the classification of joint hypermobility and related conditions.
American Journal of Medical Genetics Part C. 2017;175C:148–157.
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4
Afrin LB, Self S, Menk J, Lazarchick J.
Characterization of mast cell activation syndrome.
Immunology and Allergy Clinics of North America. 2017.
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5
The Ehlers-Danlos Society.
Clinical resources for hEDS and related conditions.
ehlers-danlos.com. Accessed 2025–2026.
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6
Fairweather D, Bruno KA, et al.
An overview of Ehlers-Danlos syndrome and the link between POTS and gastrointestinal symptoms with a focus on gastroparesis.
Frontiers in Physiology. 2024. PMC11390471.
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7
Fikree A, Akbar A, Grahame R, Costigan C, Aziz Q.
The suggested relationships between common GI symptoms and joint hypermobility, POTS, and MCAS.
Gastro-Hep Communications. 2024. PMC11348541.
These sources inform POTS diagnosis and treatment, dysautonomia in hEDS, cardiovascular screening, and autonomic nervous system considerations relevant to cardiologists.
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1
Malfait F, Francomano C, Byers P, et al.
The 2017 international classification of the Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2017;175C:8–26.
-
2
Tinkle B, Castori M, Berglund B, et al.
Hypermobile Ehlers-Danlos syndrome: Clinical description and natural history.
American Journal of Medical Genetics Part C. 2017;175C:48–69.
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3
Sheldon RS, Grubb BP, Olshansky B, et al.
2015 Heart Rhythm Society Expert Consensus Statement on the Diagnosis and Treatment of Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia, and Vasovagal Syncope.
Heart Rhythm. 2015;12(6):e41–e63.
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4
Raj SR.
Postural tachycardia syndrome (POTS).
Circulation. 2013;127(23):2336–2342.
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5
Afrin LB, Self S, Menk J, Lazarchick J.
Characterization of mast cell activation syndrome.
Immunology and Allergy Clinics of North America. 2017.
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6
Benarroch EE.
Postural tachycardia syndrome: a heterogeneous and multifactorial disorder.
Neurology. 2012;78(24):1940–1950.
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7
The Ehlers-Danlos Society.
Clinical resources for hEDS and related conditions.
ehlers-danlos.com. Accessed 2025–2026.
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8
Fairweather D, Bruno KA, et al.
An overview of Ehlers-Danlos syndrome and the link between POTS and GI symptoms.
Frontiers in Physiology. 2024. PMC11390471.
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9
Fikree A, Akbar A, Grahame R, Costigan C, Aziz Q.
The suggested relationships between common GI symptoms and joint hypermobility, POTS, and MCAS.
Gastro-Hep Communications. 2024. PMC11348541.
These sources inform small fiber neuropathy, dysautonomia, cervical instability, brain fog, proprioception deficits, and central sensitization as neurological manifestations of hEDS.
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1
Malfait F, Francomano C, Byers P, et al.
The 2017 international classification of the Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2017;175C:8–26.
-
2
Tinkle B, Castori M, Berglund B, et al.
Hypermobile Ehlers-Danlos syndrome: Clinical description and natural history.
American Journal of Medical Genetics Part C. 2017;175C:48–69.
-
3
Daylor V, Griggs M, Weintraub A, et al.
Defining the chronic complexities of hEDS and HSD: A global survey of diagnostic challenges, life-long comorbidities, and unmet needs.
Journal of Clinical Medicine. 2025;14(16):5636.
-
4
The Ehlers-Danlos Society.
Clinical resources for hEDS and related conditions.
ehlers-danlos.com. Accessed 2025–2026.
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5
Castori M, Sperduti I, Celletti C, Camerota F, Grammatico P.
Symptom and joint mobility progression in the joint hypermobility syndrome (Ehlers-Danlos syndrome, hypermobility type).
ISRN Dermatology. 2012. PMID: 23227356.
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6
Gazit Y, Nahir AM, Grahame R, Jacob G.
Dysautonomia in the joint hypermobility syndrome.
American Journal of Medicine. 2003;115(1):33–40. PMID: 12867232.
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7
Cazzato D, Castori M, Lauria G, et al.
Small fiber neuropathy is a common feature of Ehlers-Danlos syndromes.
Neurology. 2016;87(2):155–159. PMID: 27306637.
These sources inform the 2017 diagnostic criteria, Beighton score limitations, POTS and MCAS screening, fibromyalgia overlap, and differential diagnosis considerations relevant to rheumatologists.
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1
Malfait F, Francomano C, Byers P, et al.
The 2017 international classification of the Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2017;175C:8–26.
-
2
Tinkle B, Castori M, Berglund B, et al.
Hypermobile Ehlers-Danlos syndrome: Clinical description and natural history.
American Journal of Medical Genetics Part C. 2017;175C:48–69.
-
3
Daylor V, Griggs M, Weintraub A, et al.
Defining the chronic complexities of hEDS and HSD: A global survey of diagnostic challenges, life-long comorbidities, and unmet needs.
Journal of Clinical Medicine. 2025;14(16):5636.
-
4
The Ehlers-Danlos Society.
Clinical resources for hEDS and related conditions.
ehlers-danlos.com. Accessed 2025–2026.
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5
Demmler JC, Atkinson MD, Reinhold EJ, Choy E, Lyons RA, Brophy ST.
Diagnosed prevalence of Ehlers-Danlos syndrome and hypermobility spectrum disorder in Wales, UK: a national electronic cohort study and case-control comparison.
BMJ Open. 2019;9(11):e031365. PMID: 31685485. PMCID: PMC6858200.
These sources inform hormonal cycling effects on symptoms, pregnancy and postpartum considerations, gynecological manifestations, pelvic floor dysfunction, and MCAS in pregnancy.
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1
Malfait F, Francomano C, Byers P, et al.
The 2017 international classification of the Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2017;175C:8–26.
-
2
Tinkle B, Castori M, Berglund B, et al.
Hypermobile Ehlers-Danlos syndrome: Clinical description and natural history.
American Journal of Medical Genetics Part C. 2017;175C:48–69.
-
3
Daylor V, Griggs M, Weintraub A, et al.
Defining the chronic complexities of hEDS and HSD: A global survey of diagnostic challenges, life-long comorbidities, and unmet needs.
Journal of Clinical Medicine. 2025;14(16):5636.
-
4
The Ehlers-Danlos Society.
Clinical resources for hEDS and related conditions.
ehlers-danlos.com. Accessed 2025–2026.
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5
Sundelin HEK, Stephansson O, Johansson K, Ludvigsson JF.
Pregnancy outcome in joint hypermobility syndrome and Ehlers-Danlos syndrome.
Acta Obstetricia et Gynecologica Scandinavica. 2017;96(1):114–119. PMID: 27743500.
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6
Hugon-Rodin J, Lebègue G, Becourt S, Hamonet C, Gompel A.
Gynecologic symptoms and the influence on reproductive life in 386 women with hypermobility type Ehlers-Danlos syndrome: a cohort study.
Orphanet Journal of Rare Diseases. 2016;11(1):124. PMID: 27619482. PMCID: PMC5020453.
These sources inform family history patterns, pediatric symptom presentation, deferred diagnosis until skeletal maturity, and the diagnostic delay cost to children with hEDS.
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1
Malfait F, Francomano C, Byers P, et al.
The 2017 international classification of the Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2017;175C:8–26.
-
2
Tinkle B, Castori M, Berglund B, et al.
Hypermobile Ehlers-Danlos syndrome: Clinical description and natural history.
American Journal of Medical Genetics Part C. 2017;175C:48–69.
-
3
Daylor V, Griggs M, Weintraub A, et al.
Defining the chronic complexities of hEDS and HSD: A global survey of diagnostic challenges, life-long comorbidities, and unmet needs.
Journal of Clinical Medicine. 2025;14(16):5636.
-
4
The Ehlers-Danlos Society.
Clinical resources for hEDS and related conditions.
ehlers-danlos.com. Accessed 2025–2026.
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5
Tofts LJ, Simmonds J, Schwartz SB, et al.
Pediatric joint hypermobility: a diagnostic framework and narrative review.
Orphanet Journal of Rare Diseases. 2023;18(1):104. PMID: 37143135. PMCID: PMC10157984.
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6
Sokol OE, Biggs EE, Berger AS, Simons LE, Bhandari RP.
The relationship between fatigue, pain interference, pain-related distress, and avoidance in pediatric hypermobile Ehlers-Danlos syndrome.
Children (Basel). 2025;12(2):170. PMID: 40003271. PMCID: PMC11854175.
These sources inform MCAS diagnosis, mediator testing, trigger management, and the relationship between MCAS and hEDS.
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1
Malfait F, Francomano C, Byers P, et al.
The 2017 international classification of the Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2017;175C:8–26.
-
2
Tinkle B, Castori M, Berglund B, et al.
Hypermobile Ehlers-Danlos syndrome: Clinical description and natural history.
American Journal of Medical Genetics Part C. 2017;175C:48–69.
-
3
Daylor V, Griggs M, Weintraub A, et al.
Defining the chronic complexities of hEDS and HSD: A global survey of diagnostic challenges, life-long comorbidities, and unmet needs.
Journal of Clinical Medicine. 2025;14(16):5636.
-
4
The Ehlers-Danlos Society.
Clinical resources for hEDS and related conditions.
ehlers-danlos.com. Accessed 2025–2026.
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5
Kucharik M, Chang A.
Mast cell activation syndrome: a primer for the gastroenterologist.
Clinical Reviews in Allergy & Immunology. 2020.
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6
Afrin LB, Ackerley MB, Bluestein LS, et al.
Diagnosis of mast cell activation syndrome: a global “consensus-2.”
American Journal of Medical Genetics Part C. 2021.
These sources inform surgical precautions, tissue fragility, joint instability, anesthesia and wound healing considerations, and orthopedic-specific symptom management.
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1
Malfait F, Francomano C, Byers P, et al.
The 2017 international classification of the Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2017;175C:8–26.
-
2
Tinkle B, Castori M, Berglund B, et al.
Hypermobile Ehlers-Danlos syndrome: Clinical description and natural history.
American Journal of Medical Genetics Part C. 2017;175C:48–69.
-
3
Castori M, Tinkle B, Levy H, Grahame R, Malfait F, Hakim A.
A framework for the classification of joint hypermobility and related conditions.
American Journal of Medical Genetics Part C. 2017;175C:148–157.
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4
Russek LN, Block NP, Byrne E, et al.
Presentation and physical therapy management of upper quadrant hypermobility in patients with generalized hypermobility spectrum disorder and hypermobile Ehlers-Danlos syndrome.
Physical Therapy Journal. 2023.
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5
Chopra P, Tinkle B, Hamonet C, et al.
Pain management in the Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2017;175(1). First published February 10, 2017.
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6
The Ehlers-Danlos Society.
Clinical resources for hEDS and related conditions.
ehlers-danlos.com. Accessed 2025–2026.
These sources inform safe exercise programming, the Muldowney Protocol, proprioception and stabilization priorities, pacing principles, and PT-specific symptom tracking.
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1
Malfait F, Francomano C, Byers P, et al.
The 2017 international classification of the Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2017;175C:8–26.
-
2
Tinkle B, Castori M, Berglund B, et al.
Hypermobile Ehlers-Danlos syndrome: Clinical description and natural history.
American Journal of Medical Genetics Part C. 2017;175C:48–69.
-
3
Daylor V, Griggs M, Weintraub A, et al.
Defining the chronic complexities of hEDS and HSD: A global survey of diagnostic challenges, life-long comorbidities, and unmet needs.
Journal of Clinical Medicine. 2025;14(16):5636.
-
4
The Ehlers-Danlos Society.
Clinical resources for hEDS and related conditions.
ehlers-danlos.com. Accessed 2025–2026.
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5
Brittain MG, Flanagan S, Foreman L, Teran-Wodzinski P.
Physical therapy interventions in generalized hypermobility spectrum disorder and hypermobile Ehlers-Danlos syndrome: a scoping review.
Disability and Rehabilitation. 2024;46(10):1936–1953. PMID: 37231592.
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6
Castori M, Tinkle B, Levy H, Grahame R, Malfait F, Hakim A.
A framework for the classification of joint hypermobility and related conditions.
American Journal of Medical Genetics Part C. 2017;175C:148–157.
These sources inform anesthesia resistance, TMJ considerations, tissue fragility, and oral manifestations relevant to dentists and oral surgeons treating patients with hEDS.
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1
Malfait F, Francomano C, Byers P, et al.
The 2017 international classification of the Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2017;175C:8–26.
-
2
Tinkle B, Castori M, Berglund B, et al.
Hypermobile Ehlers-Danlos syndrome: Clinical description and natural history.
American Journal of Medical Genetics Part C. 2017;175C:48–69.
-
3
Daylor V, Griggs M, Weintraub A, et al.
Defining the chronic complexities of hEDS and HSD: A global survey of diagnostic challenges, life-long comorbidities, and unmet needs.
Journal of Clinical Medicine. 2025;14(16):5636.
-
4
The Ehlers-Danlos Society.
Clinical resources for hEDS and related conditions.
ehlers-danlos.com. Accessed 2025–2026.
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5
Mitakides J, Tinkle BT.
Oral and mandibular manifestations in the Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2017;175(1):220–225. PMID: 28192626.
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6
Lepperdinger U, Zschocke J, Kapferer-Seebacher I.
Oral manifestations of Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2021;187(4):520–526. PMID: 34741498.
These sources inform central sensitization, chronic pain patterns, medication considerations including LDN, and pain-specific symptom tracking in hEDS.
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1
Malfait F, Francomano C, Byers P, et al.
The 2017 international classification of the Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2017;175C:8–26.
-
2
Tinkle B, Castori M, Berglund B, et al.
Hypermobile Ehlers-Danlos syndrome: Clinical description and natural history.
American Journal of Medical Genetics Part C. 2017;175C:48–69.
-
3
Daylor V, Griggs M, Weintraub A, et al.
Defining the chronic complexities of hEDS and HSD: A global survey of diagnostic challenges, life-long comorbidities, and unmet needs.
Journal of Clinical Medicine. 2025;14(16):5636.
-
4
The Ehlers-Danlos Society.
Clinical resources for hEDS and related conditions.
ehlers-danlos.com. Accessed 2025–2026.
-
5
Chopra P, Tinkle B, Hamonet C, et al.
Pain management in the Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2017;175(1). First published February 10, 2017.
These sources inform the high prevalence of anxiety, depression, ADHD/autism overlap, medical trauma, and mental health treatment considerations in hEDS.
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1
Malfait F, Francomano C, Byers P, et al.
The 2017 international classification of the Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2017;175C:8–26.
-
2
Tinkle B, Castori M, Berglund B, et al.
Hypermobile Ehlers-Danlos syndrome: Clinical description and natural history.
American Journal of Medical Genetics Part C. 2017;175C:48–69.
-
3
Daylor V, Griggs M, Weintraub A, et al.
Defining the chronic complexities of hEDS and HSD: A global survey of diagnostic challenges, life-long comorbidities, and unmet needs.
Journal of Clinical Medicine. 2025;14(16):5636.
-
4
The Ehlers-Danlos Society.
Clinical resources for hEDS and related conditions.
ehlers-danlos.com. Accessed 2025–2026.
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5
Bulbena A, Baeza-Velasco C, Bulbena-Cabré A, et al.
Psychiatric and psychological aspects in the Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2017;175(1). First published February 10, 2017.
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6
Baeza-Velasco C.
Neurodevelopmental atypisms in the context of joint hypermobility, hypermobility spectrum disorders, and Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2021;187(4):491–499. PMID: 34741402.
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7
Bucknill E, Quadt L, Dew R, Colasanti A, Muller-Pollard CS, Critchley HD, Eccles JA.
Embracing complexity: connecting bipolar affective disorder, joint hypermobility and neurodivergence.
British Journal of Psychiatry. 2026 Jan 20:1–9. PMID: 41554535.
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8
Casanova EL, Baeza-Velasco C, Buchanan CB, Casanova MF.
The relationship between autism and Ehlers-Danlos syndromes/hypermobility spectrum disorders.
Journal of Personalized Medicine. 2020;10(4):260. PMID: 33271870.
For optometrists and ophthalmologists. Covers ocular manifestations of hEDS, connective tissue considerations, lens and retinal risk factors, and vision-specific symptom tracking.
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1
Malfait F, Francomano C, Byers P, et al.
The 2017 international classification of the Ehlers-Danlos syndromes.
American Journal of Medical Genetics Part C. 2017;175C:8–26.
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2
Gharbiya M, Moramarco A, Castori M, et al.
Ocular features in joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type: a clinical and in vivo confocal microscopy study.
American Journal of Ophthalmology. 2012;154:593–600.e1.
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3
Perez-Roustit S, Nguyen DT, et al.
Ocular manifestations in Ehlers-Danlos syndromes: clinical study of 21 patients.
Journal Français d’Ophtalmologie. 2019;42(7):722–729.
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4
The Ehlers-Danlos Society.
Clinical resources for hEDS and related conditions.
ehlers-danlos.com. Accessed 2025–2026.
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5
Kim SB, Shaia JK, et al.
Ocular manifestations in Ehlers-Danlos syndrome.
Eye (London). 2025;39(10):1990–1997. PMID: 40211016.
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6
Asanad S, Bayomi M, et al.
Ehlers-Danlos syndromes and their manifestations in the visual system.
Frontiers in Medicine. 2022;9:996458. PMID: 36237549.
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7
Moshirfar M, Barke MR, et al.
Controversy and consideration of refractive surgery in patients with heritable disorders of connective tissue.
Journal of Clinical Medicine. 2021;10(17):3769. PMID: 34501218.