PART ONE: BACKGROUND

1.0 Introduction

Ehlers-Danlos Syndromes (EDS) have been around, in some form, since at least 400 BC. However, it was not until the early 1900s that the condition was considered a distinct entity. There have a number of classifications of EDS, with the latest in 2017. Over that period, the identification of over a dozen novel genes underlying variants of EDS has enhanced the understanding of the connective tissue and added new tools for the diagnosis and management of individuals with EDS.

EDS is the most common of a group of connective tissue disorders that can be inherited and varied in their effects and causes. They are generally characterised by joint hypermobility, skin hyperextensibility, and tissue fragility. EDS are known to affect men and women of every race and ethnicity. There are numerous sub-types of EDS, of which hypermobile EDS (hEDS) is the most common.

Although EDS are increasingly diagnosed, they are still a poorly understood group of genetic disorders.

  • Part One of this article will provide the reader with a definition of Ehlers-Danlos Syndromes, other common terms by which they are known, a brief history, as well as defining some important terms.
  • Part Two will then provide a description of connective tissue, including its purpose and elements that make it up, as well as the different types. Part Two will then look at hypermobility spectrum disorders, including joint hypermobility and instability. It will also outline assessment methods for classifying generalised joint hypermobility and problems associated with it.
  • Part Three will discuss the problems associate with EDS, and the prevalence and risk factors.
  • Part Four will outline and discuss the symptoms of EDS and how it can be diagnosed.
  • Part Five looks at a variety of treatments and management for EDS, including exercise and its benefits.
  • Part Six provides a summary, useful publications and links, and references.

This article is for information only and does not constitute medical advice.

2.0 What are Elhers-Danlos Syndromes?

Ehlers-Danlos Syndromes (EDS) can be defined as:

“The Ehlers-Danlos syndromes are a group of connective tissue disorders that can be inherited and are varied both in how they affect the body and in their genetic causes. They are generally characterized by joint hypermobility (joints that stretch further than normal), skin hyperextensibility (skin that can be stretched further than normal), and tissue fragility.” (The Ehlers-Danlos Society, 2019).

Connective tissue (discussed in Part Two) is what the body uses to provide strength and elasticity; normal connective tissue holds strong proteins that allow tissue to be stretched, but not beyond its limit, and then safely return that tissue to normal. Connective tissue is found throughout the body, and EDS is considered a structural problem.

There are a variety of sub-types of EDS (Section 2.3) and there is substantial overlap between the EDS sub-types and other connective tissue disorders, for example, hypermobility spectrum disorders.

In short, EDS are/can:

  • A group of connective tissue disorders that can be inherited;
  • Varied in how they affect the body;
  • Varied in their genetic causes;
  • Characterised by joint hypermobility (joints that stretch further than normal);
  • Characterised by skin hyperextensibility (skin that can be stretched further than normal);
  • Characterised by tissue fragility; and
  • Cause symptoms throughout the body, requiring medical attention and validation.

2.1 Other Terms for Ehlers-Danlos Syndrome

EDS is generally known as:

  • Ehlers-Danlos Syndrome;
  • Ehlers-Danlos Syndromes; and
  • EDS.

2.2 Brief History

The following is a brief history of EDS (Beighton et al., 1997; Parapia & Jackson, 2008; Laferrier et al., 2018):

  • 400 BC: Hippocrates first describes individuals with joint laxity and multiple scars.
  • 1901: Edvard Ehlers recognises the condition as a distinct entity.
  • 1908: Henri-Alexandre Danlos suggests that skin extensibility and fragility are the cardinal features of the syndrome.
  • 1960’s: Formalised classification of EDS begins.
  • 1988: Significant changes in nosology made (a classification or list of diseases).
  • 1997/8: Further significant changes in nosology made.
  • 2017: Reclassification of EDS sub-types.

2.3 Types of Ehlers-Danlos Syndrome

In the 1980s, there were eleven types of EDS (Hinton, 1986):

  1. Type I: Gravis.
  2. Type II: Mitis.
  3. Type III: Benign Hypermobile (Hinton, 1986). Also known as EDS Type III and EDS Hypermobility Type (ED-HT) (Tinkle et al., 2017), and currently known as Hypermobile EDS (hEDS).
  4. Type IV: Ecchymotic.
  5. Type V: X-Linked.
  6. Type VI: Ocular.
  7. Type VII: Arthtocalasis Multiplex Congenita.
  8. Type VIII: Periodontitis.
  9. Type IX: Occipital Horn/
  10. Type X: FN Abnormality.
  11. Type XI: Familial Joint Instability Syndrome.

Genetic testing, at this point, was still in its infancy and the genetic mutations were largely unknown.

In 1997, the Villefranch conference made some changes to the classification of EDS. For example Type I and Type II were reclassified as EDS Classic Type.

In 2017, the International EDS Consortium reclassified EDS once again, in part due to greater understanding and in part to develop better nomenclature. As of 2017, there are thirteen defined types of EDS as well as a number of mutations identified as EDS that fall outside the current system (Ehlers-Danlos Society, 2019) – although EDS can be classified in one of two ways, as outlined in Tables 1 and 2. It should be noted that some medical professionals and physiotherapists still use the pre-2017 terms.

Notes:

  1. IP = inheritance pattern.
  2. AD = autosomal dominant: If you get the abnormal gene from only one parent, you can get the disease.
  3. AR = autosomal recessive: Means two copies (i.e. from both parents) of an abnormal gene must be present in order for the disease or trait to develop.

Conditions no longer included in the EDS spectrum include (Ehlers-Danlos Society, 2019):

  • Occipital horn syndrome;
  • Fibronectin-deficient (EDS X);
  • Familial articular hypermobility (EDS XI);
  • X-linked EDS with muscle haematoma (EDS V); and
  • Filamin A related EDS with periventricular nodular heterotopia.

In Table 2, the EDS sub-types are classified into groups according to similarities in the way the responsible genes affect the body.

2.4     Defining the Terms

  • Syndrome: A group of signs and symptoms that occur together and characterise a particular abnormality or condition.
  • Tissue: An aggregate of cells usually of a particular kind together with their intercellular substance that form one of the structural materials of a plant or an animal.
  • Connective Tissue: A tissue of mesodermal origin that consists of various cells (such as fibroblasts and macrophages) and interlacing protein fibres (as of collagen) embedded in a chiefly carbohydrate ground substance, that supports, ensheathes, and binds together other tissues, and that includes loose and dense forms (such as adipose tissue, tendons, ligaments, and aponeuroses) and specialised forms (such as cartilage and bone).
  • Epithelium (Epithelial Tissue): A membranous cellular tissue that covers a free surface or lines a tube or cavity of an animal body and serves especially to enclose and protect the other parts of the body, to produce secretions and excretions, and to function in assimilation.
  • Extracellular matrix: Cells of the connective tissue are suspended in a non-cellular matrix that provides structural and biochemical support to the surrounding cells.
  • Fibroblast: A type of cell found in connective tissue that synthesises the extracellular matrix and collagen.
  • Collagen: Any of a group of fibrous proteins that occur in vertebrates as the chief constituent of connective tissue fibrils and in bones and yield gelatin and glue upon boiling with water.
  • Mesodermal: The middle of the three primary germ layers of an embryo that is the source of many bodily tissues and structures (such as bone, muscle, connective tissue, and dermis).
  • Tendons: A tough cord or band of dense white fibrous connective tissue that unites a muscle with some other part (such as a bone) and transmits the force which the muscle exerts.
  • Ligaments: A tough fibrous band of tissue connecting the articular extremities of bones or supporting an organ in place.
  • Aponeuroses: A broad flat sheet of dense fibrous collagenous connective tissue that covers, invests, and forms the terminations and attachments of various muscles.
  • Hypermobility: An increase in the range of movement of which a body part and especially a joint is capable.
  • Joint Hypermobility:
    • This is a term to describe the capability of joints to move beyond normal limits.
    • It can exist by itself or be a part of a more complex diagnosis.
  • Localised Joint Hypermobility: Joint hypermobility in fewer than five joints.
  • Generalised Joint Hypermobility: Join hypermobility in five or more joints.
  • Ground Substance: A more or less homogeneous matrix in which the specific differentiated elements of a system are suspended:
    • The intercellular substance of tissues;
    • Cytosol (The fluid portion of the cytoplasm exclusive of organelles and membranes).
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