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Vascular Ehlers- Danlos in the pediatric population Shaine A. Morris, MD, MPH Pediatric Cardiology Texas Children’s Hospital, Baylor College of Medicine

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Page 1: Vascular Ehlers- Danlos in the pediatric populationehlers-danlos.com/2014-annual-conference-files/Shaine Morris.pdf · Vascular Ehlers-Danlos in the pediatric population Shaine A

Vascular Ehlers-

Danlos in the

pediatric population

Shaine A. Morris, MD, MPH

Pediatric Cardiology

Texas Children’s Hospital, Baylor

College of Medicine

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Objectives

• Learn what Vascular EDS is, and how it is different

than other forms of EDS

• Learn about what affects children with Vascular

EDS

• Learn what might be done to improve the lives of

children with Vascular EDS

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What is Vascular EDS?

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Vascular EDS

• A rare type of EDS (EDS IV) caused by a mutation in

the COL3A1 gene, which encodes part of type III

collagen (compared to classic Ehlers-Danlos, caused

by a COL5A1 mutation).

• Estimated to be present in 1 in 90,000 people

• Collagen is a tough, fiber-like protein that makes

up about a third of body protein.

• Type III collagen is found in extensible connective

tissues such as skin, lung, uterus, intestine and the

vascular system

http://compbio.cs.princeton.edu/csc/

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Vascular EDS

• Collagen is a tough, fiber-like protein that makes

up about a third of body protein.

• Type III collagen is found in extensible connective

tissues such as skin, lung, uterus, intestine and the

vascular system

http://compbio.cs.princeton.edu/csc/

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Type 3 Collagen

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Vascular EDS Overview

• Vascular Ehlers-Danlos syndrome is characterized

by:

– Thin, translucent skin, and easy bruising

– Veins are visible beneath the skin, especially on chest /

abdomen

– Unlike people with other forms of EDS, people with

Vascular EDS have skin that is soft but not overly

stretchy

– Hands and feet may appear aged

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Vascular EDS Overview

– Characteristic facial features

• Protruding eyes

• Thin “pinched” nose and lips

• Sunken cheeks

• Small chin

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Vascular EDS Overview

• Other features associated with Vascular EDS:

– Joint hypermobility (able to bend further than expected

at joints)

– Easy tearing of tendons and muscles

– Painfully swollen veins in the legs

– Lung collapse

– Slow wound healing following injury or surgery

– Arterial, intestinal, and/or uterine fragility

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Genetics of Vascular EDS

• Autosomal dominant inherited disorder caused by

type III procollagen gene (COL3A1) mutations.

– Only need 1 affected gene to have disease

– May get from 1 parent or may be spontaneous aka “de

novo”

– 50% of the COL3A1 mutations are inherited from an

affected parent, and 50% are de novo

– Each child of an affected individual has a 50% chance

of inheriting the mutation and developing the disorder.

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Vascular EDS

• Very hard to diagnose

• The vascular type accounts for less than 4% of all

Ehlers-Danlos cases and is considered the most

severe due to risk of life threatening vascular

ruptures.

• In some reports, up to 70% of cases are

diagnosed due to vascular rupture or dissection,

gastrointestinal perforation, or organ rupture is a

presenting sign.

Page 13: Vascular Ehlers- Danlos in the pediatric populationehlers-danlos.com/2014-annual-conference-files/Shaine Morris.pdf · Vascular Ehlers-Danlos in the pediatric population Shaine A

http://fineartamerica.com/featured/artwork-of-human-arterial-system-john-bavosi.html

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Aortic Dissection

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Aortic dissection

http://www.nejm.org/doi/full/10.1056/NEJMoa063232

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Aortic Dissection in Vascular EDS

• If caught in time, for patients without Vascular

EDS, surgery to replace the aorta is performed

• However, in Vascular EDS, tissue is so friable,

that surgery is often difficult

• Surgery is therefore performed only in most

severe cases, with high risk

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• Chest X-ray will NOT pick up aortic dissection or

rupture

• Must use:

– Chest Computed Tomography/Cat scan/CT scan

OR

– Chest Magnetic Resonance Imaging/MRI/MRA

Aortic Dissection in Vascular EDS

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http://www.tooloop.com/human-anatomy-intestines-liver/

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The Growing Uterus Charts, © 1985, 2006 Childbirth Connection

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Vascular EDS in Children

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Vascular EDS in children

• In children, the features most commonly identified

as the reason for testing are family history, easy

bruising/hematomas, thin skin, and joint

hypermobility

• Infants with the condition may

be born with

– Hip dislocations

– Clubfoot, which causes the foot

to turn inward and downward

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Other features

• In childhood, also may see inguinal hernia,

pneumothorax, and recurrent joint subluxation or

dislocation can occur.

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Complications in children with Vascular EDS

• Same as adults, but less common

– Aneurysms (anywhere)

– Dissection and rupture of vessels

– Less common intestinal and uterine rupture

– Significant vaginal bleeding after intercourse

– Lung collapse

– Groin hernias

– Joint dislocations

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Can we predict the course?

• Specific mutation may matter (how it alters the

Type III collagen

– If mutation results in <15% of expected levels

• More likely to have gut/uterine involvement

• Younger age at first event

Shalhub et al., J Vasc Surgery 2014

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Good news?

• Survival in children with Vascular EDS is high

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Survival in Vascular EDS

Pepin et al., Genetics in Medicine 2014

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Good news-surgery

• Although surgery on the aorta and other vessels is

difficult, it can be successful

– 13 yo had multiple aortic surgeries for aortic

aneurysms

– 15 yo had successful repair after rupture of right

subclavian artery (arm artery)

– 13 yo had stent placed in artery to intestines after

dissection, successful

Fukui et al., Annals of Thoracic Surgery 2014, Verbert et al., Acta Chir Belg 2013

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Watching can work too

• Several examples of no intervention for dissection

and later resolution

– 12 yo boy with femoral (leg) artery dissection

– Resolved with close medical and imaging follow up

Singh et al, Eur J Vasc Endovasc Surgery 2012

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Surgery in Children with Vascular EDS

• When the diagnosis is known

– Surgery is more successful

– Survival is higher

Shalhub et al., J Vasc Surgery 2014

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Prevention

• Until recently, no medical therapy to help prevent

complications of vascular EDS

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Clinical Trial

• 2010, study published in the Lancet

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Clinical trial

• Studied celiprolol

– Beta blocker: slows heart rate

– Enrolled 53 patients in France and Belgium (8

centers) with vascular EDS, assigned them

randomly to celiprolol or placebo

– Ages 15-65 years

– Medicine was increased in dose as tolerated

– Followed for 5 years

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Clinical trial

• Drug in 25 patients, 28 with no drug (placebo)

• Looked at how many patients in each group had

dissection or rupture of an artery

• Drug: 5/25 (20%) had event

• Placebo: 14/28 (50%) had event

Page 35: Vascular Ehlers- Danlos in the pediatric populationehlers-danlos.com/2014-annual-conference-files/Shaine Morris.pdf · Vascular Ehlers-Danlos in the pediatric population Shaine A

Freedom from Events

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Conclusions of study

• Celiprolol might be the treatment of choice for

physicians aiming to prevent major

complications in patients with vascular Ehlers-

Danlos syndrome.

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Summary

• Vascular EDS is rare, but very serious

• Caused by a problem with collagen formation

• Common features are thin, translucent skin, easy

bruising, and aged hands and feet

• Often picked up in adults due to arterial, intestinal

or uterine rupture

• Most often picked up in children due to family

history, easy bruising, clubfoot, hip dislocations,

skin findings

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Summary

• In cases of suspected dissection/rupture, CT scan

or MRI should be performed

• Knowing the diagnosis of vascular EDS

significantly improved outcomes

• Surgery can be done if necessary

• Celiprolol, a beta blocker medication, may prevent

adverse events in patients with vascular EDS

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Recommendations

• Seek immediate treatment for sudden unexplained pain

• Periodic screening with CT or MRI should be considered

(not invasive angiography)

• Avoid: heavy lifting, contact sports weight training

• Make sure all potentially affected family members are

screened (knowing the diagnosis saves lives)

• Unless pregnancy is intended, strict birth control regimens

should be used in sexually active young women

• Seek treatment at experienced centers when possible

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