What is EDS

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: COL5A1, COL5A1	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