Ehlers-Danlos syndrome

Ehlers-Danlos syndromes are inherited connective tissue disorders, characterised 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, semi-transparent 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.[1]Ghali N, Sobey G, Burrows N. Ehlers-Danlos syndromes. BMJ. 2019 Sep 18;366:l4966. https://www.doi.org/10.1136/bmj.l4966 http://www.ncbi.nlm.nih.gov/pubmed/31533917?tool=bestpractice.com 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.[2]De Paepe A, Malfait F. The Ehlers-Danlos syndrome, a disorder with many faces. Clin Genet. 2012 Jul;82(1):1-11. http://www.ncbi.nlm.nih.gov/pubmed/22353005?tool=bestpractice.com 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.[3]Tinkle BT, Bird HA, Grahame R, et al. The lack of clinical distinction between the hypermobility type of Ehlers-Danlos syndrome and the joint hypermobility syndrome (a.k.a. hypermobility syndrome). Am J Med Genet A. 2009 Nov;149A(11):2368-70. http://www.ncbi.nlm.nih.gov/pubmed/19842204?tool=bestpractice.com However, newer classifications have now described a spectrum for patients that ranges from joint hypermobility to hypermobility spectrum disorders to hEDS.[4]Castori M, Tinkle B, Levy H, et al. A framework for the classification of joint hypermobility and related conditions. Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):148-57. http://onlinelibrary.wiley.com/doi/10.1002/ajmg.c.31539/full http://www.ncbi.nlm.nih.gov/pubmed/28145606?tool=bestpractice.com

Classical EDS is the second most common subtype of EDS and is characterised 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.