🧬 EDS 101: What Is Ehlers-Danlos Syndrome?

Ehlers-Danlos Syndromes (EDS) are a complex group of genetic disorders that affect connective tissues, especially collagen, which is essential for the strength and elasticity of skin, joints, blood vessels, and internal organs. When collagen is abnormal, it leads to many multisystem symptoms that are often overlooked or misdiagnosed. Currently, there are 13 recognized types of EDS, each with unique clinical features and genetic markers.

The table below summarizes these subtypes along with hallmark defining symptoms.

🧪 What Does It Mean That hEDS Is a Clinical Diagnosis?

Hypermobile Ehlers-Danlos Syndrome (hEDS) is particularly challenging to diagnose, as no specific genetic test currently exists. Instead, healthcare providers rely on a checklist of clinical symptoms and history.

Some diagnostic indicators include:

• Joint hypermobility, often quantified using the Beighton score.
• History of joint issues, such as frequent dislocations or instability.
• Signs of fragile tissue, such as soft skin, atrophic scarring, or hernias.
• Systemic symptoms affecting multiple body areas.
• Exclusion of other disorders with similar presentations.

Due to these complexities and the lack of a direct biomarker, hEDS is often misdiagnosed, particularly in settings where knowledge of connective tissue disorders is limited.

🧍‍♀️ What Are the Most Common Symptoms?

EDS affects multiple systems, often in overlapping ways. Common symptoms include:

• Joint hypermobility and frequent dislocations
• Chronic musculoskeletal and neuropathic pain
• Severe fatigue
• Stretchy, fragile skin; slow healing and easy bruising
• Gastrointestinal issues (IBS, reflux, etc.)
• Autonomic symptoms: dizziness, fainting, increased heartrate
• Headaches/Migraines and “brain fog”
• Pelvic floor dysfunction, endometriosis, or organ prolapse

🔄 What Conditions Frequently Overlap With EDS? (Comorbidities)

1. Postural Orthostatic Tachycardia Syndrome (POTS)

• Affects blood circulation. Standing up causes excessive heart rate increases, dizziness, or fainting. EDS-related vascular laxity may contribute.

2. Mast Cell Activation Syndrome (MCAS)

• Inappropriate mast cell release causes allergy-like symptoms (hives, swelling, GI issues). Seen frequently in EDS patients.

3. Gastrointestinal Disorders

• IBS and gastroparesis are common due to connective tissue dysfunction in the gut wall and nervous system regulation.

4. Temporomandibular Joint Dysfunction (TMJ)

• Connective tissue laxity makes the jaw joint more prone to instability, clicking, and pain.

5. Neurological Conditions

• Tethered cord, Chiari malformation, and Craniocervical Instability (CCI) can co-occur, potentially affecting spinal cord function and sensory processing.

6. Mental Health Conditions

• Depression and anxiety are common and may stem from chronic pain, systemic inflammation, and the difficulty of living with a misunderstood illness.

7. Sleep Disorders

• Non-restorative sleep, insomnia, and fatigue may result from autonomic issues, pain, or central sensitization.

❌ Common Misdiagnoses in EDS

Patients with EDS are often misdiagnosed with conditions that resemble their symptoms but do not address the underlying connective tissue disorder:

1. Fibromyalgia

• Overlapping chronic pain and fatigue often lead to this diagnosis without recognizing joint hypermobility.

2. Chronic Fatigue Syndrome (CFS)

• Shared features like debilitating fatigue and cognitive issues often cause confusion between CFS and EDS.

3. Anxiety Disorders

• Autonomic symptoms (like racing heart or dizziness) are misattributed to anxiety, obscuring the real cause.

4. Growing Pains (in children)

• Pediatric joint pain may be written off as “normal” growth, delaying early intervention.

5. Functional Neurological Disorders

• EDS-related neurological symptoms (e.g., tremors, weakness) can be misdiagnosed as psychogenic if tests appear normal.

6. Lupus (Systemic Lupus Erythematosus)

• Because both lupus and EDS can involve fatigue, joint pain, skin sensitivity, and multi-system effects. Some EDS patients are initially evaluated or treated for lupus, especially when lab tests are inconclusive or show nonspecific inflammation.

🚧 Challenges in the Field

Despite rising awareness, significant gaps in understanding and managing EDS remain:

1. Lack of a Biomarker for hEDS

• Diagnosis relies on clinical criteria due to the absence of a known gene, contributing to misdiagnosis and limited research inclusion.

2. Limited Medical Education

• Most healthcare providers receive minimal training on EDS, leading to delayed diagnoses and inappropriate referrals.

3. Research is Underfunded

• EDS may affect 1 in 500 people, yet research funding is limited. Few large studies exist, and treatment remains largely anecdotal.

4. Fragmented and Siloed Care

• EDS affects multiple systems, but care is often split among uncoordinated specialists. Patients are left to connect the dots themselves.

5. Medical Dismissal and Gaslighting

• Especially common among women, many patients are told their symptoms are psychological or exaggerated.

6. Misinterpretation as Child Abuse

• In children, symptoms like bruising and joint instability are sometimes mistaken for signs of abuse, leading to investigations and trauma.

7. The Double-Edged Sword of Social Media

• While platforms like TikTok raise awareness, they can also spread misinformation. Some doctors now dismiss patients who mention EDS, assuming they’re self-diagnosing based on internet trends.

💡 Why It Matters

Current estimates suggest hypermobile EDS might impact 1 in 500 individuals (668,000 people in the US alone), making it one of the more commonly undiagnosed and misdiagnosed conditions in healthcare.

Early diagnosis and intervention, especially in childhood, can prevent injuries, improve quality of life, and reduce long-term disability.

🧭 Conclusion

Understanding and recognizing EDS in its many forms is crucial for guiding affected individuals toward proper care. By fostering awareness, educating providers, and supporting more research, we can move toward a future where patients are seen, supported, and believed.

References

1. Bowen JM, et al. Ehlers-Danlos syndrome, classical type. Am J Med Genet C Semin Med Genet. 175(1):27-39. DOI: 10.1002/ajmg.c.31548. → This paper discusses the clinical features, diagnostic criteria, and therapeutic strategies for managing classical EDS.

2. Malfait, F., et al. (2017). The 2017 International Classification of the Ehlers–Danlos Syndromes. Am J Med Genet C Semin Med Genet, 175(1):8-26. DOI: 10.1002/ajmg.c.31552. → This article provides an updated classification of EDS, facilitating recognition and management.

3. Karthikeyan, R., & Venkat-Raman, D. (2018). Hypermobile Ehlers–Danlos syndrome and pregnancy. Obstet Med, 11(4):160-165. DOI: 10.1177/1753495x18754577. → Cited for practical considerations regarding pregnancy-related health issues in hypermobile EDS.

4. Dhingra, K., et al. (2021). Gastrointestinal medication burden among persons with the Ehlers‐Danlos syndromes. Neurogastroenterology & Motility, 33(3):e13850. - DOI:10.1111/nmo.14077. → This study highlights the gastrointestinal complications commonly reported in individuals with EDS.

5. Vos A, Burns KM. (2021) Pediatric Innominate Artery Pseudoaneurysm Rupture in Vascular Ehlers-Danlos Syndrome: A Case Report. Clin Pract Cases Emerg Med. 5(2):226-229. - DOI: 10.5811/cpcem.2021.3.51787. → Discusses critical vascular complications in EDS from a case management perspective.

6. Chun, H. Y., et al. (2011). Type IV Ehlers-Danlos Syndrome: A Surgical Emergency? A Case of Massive Retroperitoneal Hemorrhage. Open Cardiovascular Medicine Journal, 5:21-25. DOI: 10.2174/1874192401105010210. → This paper documents surgical challenges associated with vascular EDS.

7. Semyachkina AN, et al. (2021) Ehlers-Danlos syndrome kyphoscoliotic type 2 caused by mutations in the FKBP14 gene: an analysis of five cases. F1000Res., 10:502. DOI: 10.12688/f1000research.52268.1. → Explains the complexities in the management of kyphoscoliotic EDS.

8. van Dijk FS, et al. (2024) Clinical diagnosis of the monogenic Ehlers-Danlos syndromes. Med Genet. 36(4):225-234. DOI: 10.1515/medgen-2024-2060. → Offers an extensive overview of clinical presentations and challenges across various types of EDS.

9. Kim, S. J., et al. (2020). Appendiceal torsion in Ehlers-Danlos syndrome: A case report of a rare phenomenon in a rare disease. International Journal of Surgery Case Reports, 75:133-136. DOI: 10.1016/j.ijscr.2020.06.084). → Illustrates unique surgical challenges related to EDS.

10. Scheper, M., et al. (2015). Chronic Pain in Hypermobility Syndrome and Ehlers–Danlos Syndrome (Hypermobility Type): It is a Challenge. Journal of Pain Research, 8:93-100. DOI: 10.2147/jpr.s64251. → Explores chronic pain issues within the context of hypermobility EDS, highlighting comorbidities.

11. Wright, K., et al. (2023). Delivery Outcomes and Postpartum Readmissions Associated with Ehlers–Danlos Syndrome. American Journal of Perinatology. [DOI: 10.1055/a-2185-4149](DOI: 10.1055/a-2185-4149). → Addresses the obstetric risks and challenges faced by women with EDS.

12. Cosare, A., et al. (2024). Multisystem Involvement in a Pediatric Patient With Hypermobile Ehlers-Danlos Syndrome: A Case Report of the Diagnostic Complexity and Management Challenges. Cureus, 16(4):e62083. DOI: 10.7759/cureus.62083. → Discusses complexities in diagnosis and management in pediatric patients with EDS.

13. Scicluna K, et al. (2022) Hypermobile Ehlers-Danlos syndrome: A review and a critical appraisal of published genetic research to date. Clin Genet. 101(1):20-31. DOI: 10.1111/cge.14026. → underscores the complexities of diagnosing hEDS, the need for more robust genetic research, and the importance of a standardized approach in clinical practice to ensure timely and accurate diagnosis for individuals affected by this condition.

14. Beighton P, Solomon, et al. (1973) Articular mobility in an African population. Ann Rheum Dis. 32(5):413-8. DOI: 10.1136/ard.32.5.413 → This paper introduced the now widely used 9-point Beighton scoring system for evaluating generalized joint hypermobility in population studies, which has since been adapted in clinical diagnostic criteria for hEDS and other connective tissue disorders