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.