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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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    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.

  • 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

    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

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

  • 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

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    Good news?

    • Survival in children with Vascular EDS is high

  • 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

  • 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 for

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