Vascular Ehlers- Danlos in the pediatric population
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1 Vascular Ehlers- Danlos in the pediatric population Shaine A. Morris, MD, MPH Pediatric Cardiology Texas Children s Hospital, Baylor College of Medicine
2 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 xxx00.#####.ppt 7/16/2014 3:29:59 PM
3 What is Vascular EDS? xxx00.#####.ppt 7/16/2014 3:29:59 PM
4 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 xxx00.#####.ppt 7/16/2014 3:29:59 PM
5 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 xxx00.#####.ppt 7/16/2014 3:29:59 PM
6 Type 3 Collagen xxx00.#####.ppt 7/16/2014 3:29:59 PM
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8 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 xxx00.#####.ppt 7/16/2014 3:30:00 PM
9 Vascular EDS Overview Characteristic facial features Protruding eyes Thin pinched nose and lips Sunken cheeks Small chin xxx00.#####.ppt 7/16/2014 3:30:00 PM
10 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 xxx00.#####.ppt 7/16/2014 3:30:00 PM
11 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. xxx00.#####.ppt 7/16/2014 3:30:00 PM
12 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. xxx00.#####.ppt 7/16/2014 3:30:00 PM
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15 Aortic Dissection xxx00.#####.ppt 7/16/2014 3:30:00 PM
16 Aortic dissection xxx00.#####.ppt 7/16/2014 3:30:00 PM
17 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 xxx00.#####.ppt 7/16/2014 3:30:00 PM
18 Aortic Dissection in Vascular EDS 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 xxx00.#####.ppt 7/16/2014 3:30:00 PM
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20 The Growing Uterus Charts, 1985, 2006 Childbirth Connection
21 Vascular EDS in Children xxx00.#####.ppt 7/16/2014 3:30:00 PM
22 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 xxx00.#####.ppt 7/16/2014 3:30:01 PM
23 Other features In childhood, also may see inguinal hernia, pneumothorax, and recurrent joint subluxation or dislocation can occur. xxx00.#####.ppt 7/16/2014 3:30:01 PM
24 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 xxx00.#####.ppt 7/16/2014 3:30:01 PM
25 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 xxx00.#####.ppt 7/16/2014 3:30:01 PM
26 Good news? Survival in children with Vascular EDS is high xxx00.#####.ppt 7/16/2014 3:30:01 PM
27 Survival in Vascular EDS Pepin et al., Genetics in Medicine 2014
28 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 xxx00.#####.ppt 7/16/2014 3:30:01 PM
29 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 xxx00.#####.ppt 7/16/2014 3:30:01 PM
30 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 xxx00.#####.ppt 7/16/2014 3:30:01 PM
31 Prevention Until recently, no medical therapy to help prevent complications of vascular EDS xxx00.#####.ppt 7/16/2014 3:30:01 PM
32 Clinical Trial 2010, study published in the Lancet xxx00.#####.ppt 7/16/2014 3:30:01 PM
33 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 years Medicine was increased in dose as tolerated Followed for 5 years xxx00.#####.ppt 7/16/2014 3:30:01 PM
34 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 xxx00.#####.ppt 7/16/2014 3:30:01 PM
35 Freedom from Events
36 Conclusions of study Celiprolol might be the treatment of choice for physicians aiming to prevent major complications in patients with vascular Ehlers- Danlos syndrome. xxx00.#####.ppt 7/16/2014 3:30:01 PM
37 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 xxx00.#####.ppt 7/16/2014 3:30:01 PM
38 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 xxx00.#####.ppt 7/16/2014 3:30:01 PM
39 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 xxx00.#####.ppt 7/16/2014 3:30:01 PM
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