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Writer's pictureMatthew Preston

An overview of the different types of EDS

Updated: Dec 13, 2018


DNA strand double helix genetics gene

Who: Dr Felicity Collins, Clinical Geneticist, Royal Alfred Clinic, Australia

What: Ehlers-Danlos Society Learning Conference - Patient Day

Where: Macquarie University, Sydney

When: 8 December 2018


These are my notes from Dr Collins' talk. I have tried to be as true as possible to what was said at the conference, but please excuse any errors.


HYPERMOBILITY:

- Clinical Diagnosis of Hypermobility: 'range of joint movement that exceeds what is considered to be normal, taking into account the individual's age, gender and ethnic background (Asians and Africans are more hypermobile)'

- Hypermobility tends to run in families

- Many conditions have increased flexibility: Sotos syndrome, Fragile X, Downs Syndrome, etc.

- Sometimes it is hard to tell if it is a primary neuromuscular or connective tissue problem: myopathies can be associated with joint hypermobility.

- Often there is an overlap: eg, Marfan Syndrome

- Different perspectives: neuromuscular disorders, myalgic encephalomyelitis (Chronic Fatigue Syndrome), mixed connective tissue disorder, Fibromyalgia

- Is hypermobility in itself a connective tissue disorder?


CONNECTIVE TISSUES IN THE BODY include epithelial - skin, muscles, nerves, connective tissue ('scaffolding')


TYPES OF CONNECTIVE TISSUE:

- loose connective tissue

  • joining skin to muscles

  • provides strength, elasticity and support

- dense connective tissue

  • collagen fibres and fibroblasts

  • tendons and ligaments, bone, cartilage

  • meshlike framework in skin

- elastic connective tissue

  • walls of arteries, blood vessels, airways

EHLERS-DANLOS SYNDROMES

- Defining Ehlers-Danlos Syndromes: major breakthroughs in 1997 and 2016

- Most common forms of EDS:

  • Hypermobile EDS (hEDS) ~1/2,500-5,000 (possibly more common)

*Currently hEDS is a 'genetic big black hole' - the responsible gene(s) are unknown

*Likely 'polygenic': changes in more than one gene

*Genetics always depends on what you inherit plus environmental factors

*Because the genetic basis for hEDS is still unknown, clinical diagnosis and proper management of an individual's symptoms are important - based on criteria.

  • Classical EDS (cEDS) ~1/10,000

*Hypermobile like hEDS but with the addition of stretchy skin and unusual scarring

  • Vascular EDS (vEDS) ~1/50,000

*Affects Type III collagen

*Most dangerous type: reduced lifespan - median 49 yr men, 53 yr women


- EDS is genetic and usually 'runs in families': one type 'runs true' within each family (all affected individuals have the same type of EDS but may vary greatly in symptoms and severity) - some rare exceptions??


- Types of genetic inheritance:

  • Autosomal Dominant (AD): 50% chance of each child getting EDS; EDS passed on generation to generation (hEDS, cEDS, vEDS are all AD)

  • Autosomal Recessive (AR): brothers and sisters in one family affected; less variability within the family - usually not generation to generation

GENETIC TESTING:

- Most important when vEDS is suspected

- Reasons to consider genetic testing in individuals with hEDS:

  • Exclude other diagnoses in a patient who has features suggestive of another form of EDS (especially vEDS)

  • Research purposes: contribute to EDS research to help find the gene(s) responsible

- Why not test everyone with suspected hEDS?

  • No known gene(s) yet for hEDS and it is by far the most common type

  • It is expensive and there is a shortage of geneticists

- Note about genetic testing in NZ: Genetic testing is unlikely to be done in the public health system unless Vascular EDS is highly suspected.

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