This is a brief summary of Ehlers-Danlos syndrome (EDS), and the different types that are described in the 2017 Classification of EDS (Malfait et al, 2017). It is aimed at health and social care professionals and lay people and as quick guide to the variety of issues that might arise. At the bottom of this article we have also linked the reader to more information on the Ehlers-Danlos Support - UK (EDS-UK) website, and to the open access articles published in March 2017 under the American Journal of Medical Genetics, Seminars series.

Introduction

Ehlers-Danlos syndrome is a group of conditions that arise from genetic alterations in collagen. Collagens are proteins found throughout the body. There are a number of different types of collagen in the body, often found together in very particular combinations in different body tissues. We all make the same collagens, distributed throughout the body in the same way. The collagens give strength and support to, for example, skin, bone, blood vessels, the gut, and tissues in and around joints such as ligaments, tendons and cartilage.

The production of each type of collagen is genetically determined. Alterations to the genes that are responsible for either making collagen or allowing it to function properly can result in weaker or more fragile and stretchy tissues throughout the body. As a consequence of this certain physical findings and complications arise. It is the recognition of these patterns of physical signs and the identification of specific gene alterations that allow clinicians to separate out the different types of EDS.

The Different types of EDS

There are several forms of EDS. Looking through the list of types might seem a little daunting, but for the majority of individuals the diagnosis is most likely to be the Hypermobile type (hEDS), followed by the Classical (cEDS), then the Vascular type (vEDS).

All share common features, such as flexibility (hypermobile) and often instability (subluxation or dislocation) at the joints; abnormal skin (from mild papyraceous scars and stretchmarks in hEDS to severe atrophic scars in cEDS; and other fragile body tissues e.g., weak abdominal wall leading to hernias, stretchy blood vessels and varicose veins, and thin heart valves. However, some types have more severe physical signs than others, and some have unique characteristics too.

Apart from the Hypermobile type (for which there is no definitive genetic test at present), genetic abnormalities have been found in most types of EDS but may not be easily identifiable in every case.

Table 1 shows the 2017 classification of EDS.

Table 1: The Classification of the Ehlers-Danlos Syndromes, Inheritance Pattern, and Genetic Basis (Malfait et al, 2017)

Clinical EDS subtype Abbreviation Inheritance Pattern Genetic Basis Protein
1. Classical EDS cEDS AD Major: COL5A1COL5A1 Type V collagen
Rare: COL1A1 Type I collagen
c.934C>T, p.(Arg312Cys)
2. Classical-like EDS clEDS AR TNXB Tenascin XB
3. Cardiac-valvular  cvEDS AR COL1A2 (biallelic mutations that lead to COL1A2 NMD and absence of pro α2(I) collagen chains) Type I collagen
4. Vascular EDS vEDS AD Major Major: COL3A1
Rare: COL1A1
c.934C>T, p.(Arg312Cys)
c.1720C>T, p.(Arg574Cys)
c.3227C>T, p.(Arg1093Cys)
5. Hypermobile EDS hEDS AD Unknown Unknown
6. Arthrochalasia EDS aEDS AD COL1A1, COL1A2 Type I collagen
7. Dermatosparaxis EDS dEDS AR ADAMTS2 ADAMTS-2
8. Kyphoscoliotic EDS kEDS AR

PLOD1

FKBP14

LH1

FKBP22

9. Brittle Cornea syndrome BCS AR

ZNF469

PRDM5

ZNF469

PRDM5

10. Spondylodysplastic EDS spEDS AR

B4GALT7

B3GALT6

SLC39A13

β4GalT7

β3GalT6

β3GalT6

11. Musculocontractural EDS mcEDS AR

CHST14

DSE

D4ST1

DSE

12. Myopathic EDS mEDS AD or AR COL12A1 Type XII collagen
13. Periodontal EDS pEDS AD

C1R

C1S

C1r

C1s

 
There are a number of more rare types of EDS, notably Atherochalasia, Dermatospraxis, and Kyphoscolitic (Brady et al, 2017). The reader is directed to the EDS-UK website for more information on these types of EDS by clicking HERE. Also, the references below are available as open access papers by clicking HERE.
Dr Alan J Hakim MA FRCP
Consultant Physician and Rheumatologist, Chief Medical Advisor and Trustee, HMSA
Review date: March 2018

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