vascular ehlers- danlos in the pediatric...
TRANSCRIPT
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
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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 <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
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 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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