Latest News

Diagnosing EDS

Posted By Alan Hakim, June 29, 2013

The Classification and Diagnostic Criteria of Ehlers-Danlos Syndrome

This article has been written to inform members of the public and healthcare professionals about the diagnosis and classification of EDS.

These are based on both clinical features, the degree of severity of these clinical features, and the presence of specific genetic abnormalities.

This was first described as the Villefranche Nosology in 1997 and has been updated as more is understood of the genetics. The classification was changed from its original numerical one to a more descriptive one i.e. Type I and II are now called ‘Classic’. It remains under regular review by an international body of experts.

In the table below the criteria are shown as Major and Minor features.

The term IP refers to the type of genetic ‘penetrance’ in families i.e. whether it is Autosomal ‘Dominant’ (AD) or ‘Recessive’ (AR).

For every characteristic we have (e.g., our hair colour, eye colour etc) we have two copies of the gene. One of this pair may be stronger than the other i.e. ‘Dominant’, and the proteins/molecules/structures it codes for over-ride others produced by the other gene in the pair. This dominance is then seen through the generations. If one parent has 1 dominant gene for a condition and the other parent has none then there is a 50:50 chance of an offspring inheriting the gene and expressing the condition. If both parents have 1 dominant gene there is a 75% chance of an offspring inheriting the gene (and a 25% chance that the offspring will inherit the dominant gene from both parents). If someone has 2 dominant genes (i.e. both genes in the pair) then there is a 100% chance of passing this on to the next generation.

Some genes are described as ‘Recessive’. Their effect, i.e. proteins / structures etc may not have any effect / influence if there is a stronger effect from the dominant paired gene. For a recessive disorder to be expressed clinically in an offspring both copies of the gene (one from each parent) need to be recessive. Often parents will be ‘carriers’ – they have one copy of the gene that is recessive but suppressed by the other, and therefore do not show any clinical signs. However, when each parent then passes on their copy of the recessive gene to a child, the child has 2 recessive genes and so the gene and the condition or characteristic is expressed.

There is an opposite effect: one parent may have 2 recessive genes, but the other parent have no recessive genes. The second parents’ genes will dominate and as such offspring are ‘carriers’ and may not show any of the recessive condition or characteristics; the condition seems to ‘skip’ a generation.

If you and your family are undergoing genetic testing for EDS then your geneticist, genetics counsellor, or doctor will explain this to you in more detail.

A more detailed description of the different types of EDS and their management can be found by clicking Here

Dr Alan Hakim MA FRCP. Consultant Rheumatologist, Barts Health NHS Trust, London.

Written July 2013. Version 1.1. Planned date of review 2016.

Academic Reference

Beighton P, De Paepe A, Steinmann B et al 1998 Ehlers Danlos syndromes: revised nosology, Villefranche 1997. Ehlers Danlos National Foundation (USA) and Ehlers Danlos Support Group (UK). Am J Med Gen 77: 31-37


Type

Clinical Manifestations

IP

Protein

Gene

Major criteria

Minor criteria

 

 

 

Classic

(type I/II)

 

 

 

 

 

 

 

·       skin hyperextensibility

·       widened atrophic scarring

·       joint hypermobility

·       easy bruising

·       smooth and velvety skin

·       molluscoid pseudotumors

·       subcutaneous spheroids

·       muscular hypotonia

·       complications of joint hypermobility

·       surgical complications

·       positive family history

AD

Type V procollagen

(~50%)

COL5A1

COL5A2

Hypermobility 

(type III)

 

 

·       generalized joint hypermobility

·       mild skin involvement

·       recurring joint dislocations

·       chronic joint pain

·       positive family history

AD

Tenascin X (~5%)

TNX-B

Vascular

(type IV)

 

 

 

 

 

 

 

 

 

 

 

·       excessive bruising

·       thin, translucent skin

·       arterial/intestinal/

uterine fragility or rupture

·       characteristic facial appearance

·       acrogeria

·       early-onset varicose veins

·       hypermobility of small joints

·       tendon and muscle rupture

·       arteriovenous or carotid-cavernous sinus fistula

·       pneumo (hemo)thorax

·       positive family history, sudden death in close relative(s)

AD

Type III procollagen