Ehlers-Danlos Syndrome (EDS)

What is Ehlers-Danlos Syndrome, or EDS?

In the scientific literature, the acronym hEDS is often used to describe a collection of terms: EDS hypermobility type, EDS type III, and Joint Hypermobility Syndrome (JHS). While there are other EDS types that have genetic signatures, hEDS does not yet have an identifiable genetic type. However, it often is familial.

About ten million people in the United States have hypermobility syndrome, with hEDS comprising about 80-90% of those with EDS. The two most common ways that hEDS presents itself are: (1) with a small number of painful or unstable joints; or (2) with widespread musculoskeletal pain, often labeled as fibromyalgia.

As in other chronic pain syndromes, a variety of other diagnoses can overlap with hEDS: anxiety, depression, headaches, irritable bowel syndrome, chronic fatigue, TMJ problems, and sleep problems. The amount of joint laxity does not predict the amount of distress and disability in hEDS.

There seem to be two types of pain in hEDS. One is nociceptive pain related to tight muscles, or loose connective tissue at joints. The other is called neuropathic pain, which is more of an abnormal nerve signaling type of pain, typically associated with sensitivity to even light touch over different areas of the body (“allodynia”), and pain experiences such as “electric, tingling, numb, or burning.” Typically, the affected individual’s EEG, EMG, nerve conduction studies, and brain/spine imaging are all negative. Over time, with central sensitization, more areas of the body can become painful and chronic regional pain syndrome (CRPS) can develop.

Fatigue is a common syndrome in hEDS -- but is also common in adolescents overall, with studies showing that 1/3 of teens have fatigue that can interfere with school performance and attendance.

Chronic fatigue lasting six months or more without benefitting from more sleep occurs in less than 1% of adolescents. While fatigue -- even chronic fatigue -- is common in hEDS, other factors can contribute to the fatigue, such as pain, insomnia, dysautonomia, medications, and even allergies.

HEDS with fatigue is associated with more pain, functional impairment, and psychological distress. Fatigue itself can be associated with fear of physical activity and thus “kinesiophobia” can limit activity and add to fatigue. This, in turn, can decrease muscle control and coordination, which increases the risk for injuries. Decreased activity can add to feelings of fatigue and insomnia, and thus impact cognition and memory.

While the list of associated symptoms can be daunting, not all adolescents and young adults with hEDS have all such symptoms, and it is unclear what is primarily due to hEDS and what is linked to other co-occurring symptoms. For example, in hEDS, there is an increased association with anxiety, depression, affective disorder, low self-confidence, negative thinking, hopelessness, and feelings of desperation.

The best treatment approach is that of a “coordinated team” of clinicians communicating with each other and working together. The team’s goals should be improving function, sleep, and feelings of well-being, while reducing fatigue, and making lifestyle changes such as healthy eating and pacing in physical activities.

Social support is important. Psychological intervention may be needed to improve self-confidence, enhance resilience, and reduce anxiety and depression. Aquatherapy is often ideal, and pacing in physical therapy is important, especially to help teens with hEDS to reduce kinesiophobia.

In summary, hEDS is a heritable connective tissue disorder without a clear etiology, which represents up to 3% of the population. It can be multisystemic, but with primary musculoskeletal manifestations. Other co-conditions such as fatigue, pain, POTS, insomnia, and anxiety may or may not be related to the primary condition, but require attention and management.

For those who would like to do more research, below are links to some excellent articles on Ehlers-Danlos syndrome:

1. Hypermobile Ehlers-Danlos syndrome (a.k.a. Ehlers-Danlos syndrome Type III and Ehlers-Danlos syndrome hypermobility type): Clinical description and natural history. Tinkle B, et al; Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):48-69.

2. Ehlers-Danlos syndrome--a historical review. Parapia LA, Jackson C. Br J Haematol. 2008 Apr;141(1):32-5.

3. The evidence-based rationale for physical therapy treatment of children, adolescents, and adults diagnosed with joint hypermobility syndrome/hypermobile Ehlers Danlos syndrome. Engelbert RH, et al. Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):158-167.

4. Clinical and genetic aspects of Ehlers-Danlos syndrome, classic type. Malfait F, et al. Genet Med. 2010 Oct;12(10):597-605. PMID: 20847697 Review.

5. Molecular Genetics and Pathogenesis of Ehlers-Danlos Syndrome and Related Connective Tissue Disorders. Ritelli M, Colombi M. Genes (Basel). 2020 May 13;11(5):547.

6. Gastrointestinal disorders in joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type: A review for the gastroenterologist. Beckers AB, et al. Neurogastroenterol Motil. 2017 Aug;29(8).

7. Ehlers-Danlos syndrome: how to diagnose and when to perform genetic tests. Sobey G.Arch Dis Child. 2015 Jan;100(1):57-61.

8. Exercise beliefs and behaviours of individuals with Joint Hypermobility syndrome/Ehlers-Danlos syndrome - hypermobility type. Simmonds JV, et al. Disabil Rehabil. 2019 Feb;41(4):445-455.

9. Symptomatic Joint Hypermobility: The Hypermobile Type of Ehlers-Danlos Syndrome and the Hypermobility Spectrum Disorders. Tinkle BT, Levy HP.Med Clin North Am. 2019 Nov;103(6):1021-1033.

10. Hypermobile Ehlers-Danlos syndromes: Complex phenotypes, challenging diagnoses, and poorly understood causes. Gensemer C, et al. Dev Dyn. 2021 Mar;250(3):318-344.

11. Chronic fatigue in Ehlers-Danlos syndrome-Hypermobile type. Hakim A, et al. Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):175-180.

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Lonnie Zeltzer, MD, CHYP's founder and President, is an Emerita Distinguished Research Professor of Pediatrics, Anesthesiology, Psychiatry and Biobehavioral Sciences at the David Geffen School of Medicine at UCLA and Immediate Past-Director of the UCLA Pediatric Pain and Palliative Care Program. She is a co-author on the Institute of Medicine report on Transforming Pain in America and is a member of the national steering committee assigned to provide directions for pain research at the National Institutes of Health. She has received a Mayday Pain and Policy Fellowship and the 2005 Jeffrey Lawson Award for Advocacy in Children’s Pain Relief from the American Pain Society. Her research includes yoga, mindfulness, hypnotherapy, and other self-help interventions, including mobile technologies, to help children and adolescents who have chronic pain, as well as understanding biopsychosocial pain mechanisms in irritable bowel syndrome, cancer, sickle cell disease, headaches, dysmenorrhea, and other conditions. She has over 350 research publications on childhood pain and complementary therapies, has written more than 80 chapters, and published 3 books for patients and parents on pediatric chronic pain.