Ehlers-Danlos syndromes are inherited connective tissue disorders, characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Hypermobile Ehlers-Danlos syndrome (EDS) is the most common of 13 subtypes.
Many affected people are asymptomatic or develop only minor symptoms. Most hypermobile people are not aware of the fact and assume that everyone is as flexible as they are.
Skin manifestations include soft, silky skin texture, semitransparent dermis, and hyperelasticity. Patients commonly demonstrate easy bruising, scarring, and poor wound healing.
In addition to musculoskeletal and skin manifestations, cardiovascular and gastrointestinal features, autonomic dysfunction, features of chronic pain syndrome, and marfanoid habitus are often present.
Definitive diagnosis for all subtypes of EDS, except hypermobile EDS, can be made by molecular genetic testing. The genetic basis of hypermobile EDS remains unknown and the diagnosis is made by clinical criteria only.
Recommendations are primarily based on expert opinion. Therapy is tailored to individual needs. Multidisciplinary input may be necessary.
Many patients live healthy, unaffected lives and may never come to clinical attention, particularly those with hypermobile EDS. Vascular EDS is associated with a shortened lifespan due to susceptibility to arterial or visceral rupture.
Ehlers-Danlos syndromes (EDS) are a group of inherited connective tissue disorders. They are caused by pathogenic variants affecting genes encoding for, or modifying, collagen, fibrillin, and/or other matrix proteins.
Ehlers-Danlos syndromes have similar phenotypes with varying degrees of expression that may include joint hypermobility, skin hyperelasticity, easy bruising, atrophic scars, and marfanoid habitus.
There are numerous subtypes of EDS, of which hypermobile EDS (hEDS) is the most common. Previously hEDS was considered synonymous with benign joint hypermobility syndrome, sharing debilitating, yet often overlooked, associations with autonomic dysfunction, chronic pain, anxiety/phobic states, gastrointestinal dysmotility, and chronic fatigue. However, newer classifications have now described a spectrum for patients that ranges from joint hypermobility to hypermobility spectrum disorders to hEDS.
Classical EDS is the second most common subtype of EDS and is characterized by skin hyperextensibility, atrophic scarring, and impaired wound healing.
The most catastrophic subtype is vascular EDS, which is associated with blood vessel rupture and visceral perforation, and may have life-threatening consequences.
History and exam
Key diagnostic factors
- family history of joint hypermobility, EDS, or genetic mutations
- joint hypermobility
- joint or spine pain
- motor delay in infancy
- chronic pain syndrome
- recurrent joint dislocation or subluxation
- muscle pain and/or muscle spasm
- soft, silky skin texture
- semitransparent skin
- thin and stretchy double fold of skin
- atrophic scars
- easy bruising
- stretch marks
- poor wound healing and/or wound dehiscence
- significant injury
- history of delayed onset of local anesthesia
Other diagnostic factors
- muscle hypotonia
- varicose veins
- abdominal wall, inguinal, or paraumbilical hernia
- uterine or rectal prolapse
- orthostatic hypotension (OH)
- orthostatic intolerance
- postural orthostatic tachycardia syndrome (POTS)
- neurally mediated hypotension (NMH)
- marfanoid habitus
- gastrointestinal (GI) manifestations
- gynecologic manifestations
- eye abnormalities
- midsystolic click or late systolic murmur
- family history of joint hypermobility or EDS
- genetic mutations
1st investigations to order
- clinical diagnosis
- genetic testing
Investigations to consider
- complete blood count
- clotting screen
- tilt-table testing
- x-ray spine
- gastrointestinal (GI) imaging and endoscopy
Shweta Dhar, MD, MS, FACMG
Director, Adult Genetics
Department of Molecular & Human Genetics
Baylor College of Medicine
Chief, Section of Genetic Medicine
Michael E. Debakey Veterans Affairs Medical Center
SD is on the board of directors of the American College of Medical Genetics and Genomics and is a member of the Ehlers-Danlos Society International Consortium. She has previously consulted for Acer Therapeutics and has previously held shares in PanGenomics, India.
Dr Shweta Dhar would like to gratefully acknowledge Dr Rodney Grahame and Dr Alan Hakim, the previous contributors to this monograph. RG and AH are authors of several references cited in this monograph.
Howard P. Levy, MD, PhD
Division of General Internal Medicine
Department of Medicine
McKusick-Nathans Institute of Genetic Medicine
Johns Hopkins University
HPL is an author of a number of references cited in this monograph.
Bert Callewaert, MD
Fund for Scientific Research
Flanders Centre for Medical Genetics
Ghent University Hospital
BC declares that he has no competing interests.
Howard Bird, MA, MD, FRCP
Professor of Pharmacological Rheumatology
University of Leeds
Chapel Allerton Hospital
HB declares that he has no competing interests.
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- The 2017 international classification of the Ehlers-Danlos syndromes
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