While rare, Ehlers-Danlos syndrome (EDS) can be life-threatening, with some patients experiencing an arterial dissection, aneurysm rupture, or sudden death before it is identified.

Ehlers-Danlos syndrome is a group of heritable connective tissue disorders with 13 currently known subtypes — 12 of which can be diagnosed through genetic testing. Understanding the key red flags can help ensure patients are diagnosed and managed before a potentially life-altering – or even fatal – complication occurs.

Dr Kunal Verma, Australia’s first dual trained cardiologist and geneticist, explains…

Hypermobility: the hallmark of EDS

Hypermobility is the characteristic feature across all EDS subtypes, but it’s important to remember this is a physical trait like height and eye colour. There are billions of people in the world who would be hypermobile according to the normal distribution of joint mobility, so in itself this is not a marker of something serious.

Other features

Hypermobility accompanied by any of the following features is more suspicious of EDS.

1. Very significant musculoskeletal problems

These can include clubfoot requiring surgery, extreme weakness and myopathy from early life, and severe scoliosis requiring surgical intervention in childhood or adolescence.

In cases where surgery for idiopathic scoliosis is appropriate, for example, it should be a red flag to ask why this young person’s back has become so scoliotic? Could this be a connective tissue disorder?

2. Vascular and internal organ complications

Aneurysms, dissections and internal organ rupture occur more commonly in people with vascular EDS.

3. Unusual ocular problems in childhood or young adulthood

Examples include severe myopia, lens dislocation, unexplained retinal detachment, or extremely thin corneas prone to rupture.

4. Poor wound healing

Fragile, friable skin can be very difficult to suture, and patients may experience delayed or failed wound healing.

EDS subtypes

Hypermobile EDS (hEDS) is the most common subtype—and the only one that cannot be diagnosed through genetic testing because we don’t yet know which specific gene is involved. It is probably more common than previously thought; most recent estimates are a prevalence of around 1 in 500 people.

People with hypermobile EDS don’t generally have serious eye, musculoskeletal, blood vessel or heart issues. They do however have a constellation of pathologies that can be identified on imaging, along with some common symptoms.

These include:

• Clear hypermobility (a definitive feature), often accompanied by joint pain and a history of repeated joint sprains, subluxations or dislocations
• A Marfanoid appearance, with very long fingers (arachnodactyly), tall, lean build, and very soft, hyperextensible skin
• Mitral valve prolapse on echocardiogram
• Mild aortic dilatation
• Severe fatigue, gastrointestinal and neurological problems.

While hypermobile EDS doesn’t typically result in life-threatening complications, it significantly impacts quality of life and often takes decades to diagnose, causing considerable distress for patients and families.

Rarer but more serious subtypes

Classical EDS

Classical EDS occurs in about 1 in 10,000 people. While similar to hypermobile EDS, people with classical EDS tend to scar very badly. Their skin is marked by very thin scars you can almost see through, sometimes called ‘cigarette paper scarring.’

Vascular EDS

Vascular EDS is one of the more serious type of Ehlers-Danlos, with significant risk of sudden death, pregnancy complications, and surgical complications (such as bowel rupture during a gastroscopy).

People with vascular EDS often have near-translucent skin you can see their veins through, very tight facial skin, a characteristic “pinched nose” and very brittle connective tissues.

Managing vascular EDS

The severity of vascular EDS varies widely: some patients experience life-threatening events early in life, while others only discover they have it after another family member is diagnosed—having come through high-risk situations (like pregnancy or surgery) unscathed themselves.

Management involves strict blood pressure control and careful consideration before patients undergo any procedures.

Women with vascular EDS are advised against falling pregnant due to the well-documented risks of maternal and foetal death during pregnancy. Some centres can offer pregnancy care to patients with vascular EDS who choose to carry a pregnancy.

Diagnosis and genetic testing

EDS diagnosis is best made through a specialist genetic service. While GPs can order EDS genetic testing, there’s no Medicare rebate and they typically cost $1,000-$2,000.

Specialist clinics have funding to run genetic tests. They can also conduct a thorough assessment to screen for other genetic connective tissue disorders (such as Marfan syndrome), order customised genetic panels, and provide genetic counselling.

This involves pre-test counselling to discuss the implications of a positive result and help people decide whether to go ahead, followed by post-test counselling to explain the results. If genetic variants are identified, relatives may be offered testing.

When to refer

In patients with hypermobility, consider referral to a specialist genetic service if they have a personal or family history of any of the following high-risk features:

• unexplained aneurysms, artery dissections, or sudden death (e.g. an uncle who was a strong swimmer who drowned at the beach for no apparent reason)
• severe musculoskeletal issues, such as scoliosis that necessitates surgery
• severe or unexplained ocular problems
• unexplained organ rupture or recurrent organ prolapse without provocation

Importantly, specialist genetics service Australia-wide are only able to accommodate patients with high-risk features (above). Patients without high-risk features may still have EDS, but it is probably the hypermobile EDS type that carries a lower risk of serious life-threatening complications.

Supporting patients in primary care

Diagnosis is challenging and sometimes takes decades. Many patients report they have been told their symptoms are “growing pains” or psychological, leading to significant distress. Getting a name for the condition often provides relief.

GPs may be involved in co-ordinating care between various specialties. It’s important to connect patients with EDS-aware allied health professionals (physiotherapists or exercise physiologists) who can provide ongoing care.

Key takeaways

• Consider hEDS in hypermobile young people with joint issues and multi-system problems that don’t fit standard diagnostic categories.
• Never ignore EDS red flags: unexplained aneurysms/dissections, unexplained sudden death, severe skeletal/ocular complications. Refer these patients to a genetics service.
• Women with vascular EDS should be advised to avoid a pregnancy.
• Patients should be referred allied health professionals who are EDS-aware for ongoing care.

Helpful resources:

• Progenics | Dr Verma’s website has information for patients and clinicians
• Connective Tissue Disorders Network Australia | Australia’s peak body and advocate for people with heritable connective tissue disorders
• Resources list | Diagnostic criteria, management frameworks and more
• Rare Portal Ehlers-Danlos Syndrome page | Information and guidance for clinicians

Dr Verma has a dedicated phone line to support GPs across Australia. This is his Australia-wide service for health professionals who would like advice on cardiac genetics including heritable connective tissue disorders such as Marfan and Ehlers-Danlos, a history of unexplained & serious cardiovascular pathology, and critically unwell patients (cardiac arrest, cardiogenic shock) who may benefit from urgent genetic testing or storage of a DNA sample.

Doctors Line: 03 7036 0990
During business hours, the team will send him an SMS and he’ll return your call as soon as possible.