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Disease Profile

Vascular Ehlers-Danlos syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

Q79.6

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Ehlers Danlos syndrome, ecchymotic type; Ehlers Danlos syndrome, arterial type; Ehlers Danlos syndrome, Sack-Barabas type;

Categories

Blood Diseases; Congenital and Genetic Diseases; Connective tissue diseases;

Summary

Vascular Ehlers-Danlos syndrome is an inherited connective tissue disorder that is caused by defects in a protein called collagen. It is generally considered the most severe form of Ehlers-Danlos syndrome (EDS). Common symptoms include thin, translucent skin; easy bruising; characteristic facial appearance; and fragile arteries, muscles and internal organs.[1][2] Vascular EDS is usually caused by a change (mutation) in the COL3A1 gene. Rarely, it may be caused by a mutation in the COL1A1 gene.[3] Inheritance is autosomal dominant.[2] Treatment and management is focused on preventing serious complications and relieving signs and symptoms.[2][4]

Symptoms

The signs and symptoms of vascular Ehlers-Danlos syndrome vary but may include:[2][1]

  • Fragile tissues (including arteries, muscles and internal organs) that are prone to rupture
  • Thin, translucent skin
  • Characteristic facial appearance (thin lips, small chin, thin nose, large eyes)
  • Acrogeria (premature aging of the skin of the hands and feet)
  • Hypermobility of small joints (i.e. fingers and toes)
  • Early-onset varicose veins
  • Pneumothorax
  • Easy bruising
  • Joint dislocations and subluxations (partial dislocations)
  • Congenital dislocation of the hips
  • Congenital clubfoot
  • Receding gums

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal eyelash morphology
Abnormal eyelashes
Abnormality of the eyelashes
Eyelash abnormality

[ more ]

0000499
Abnormal oral frenulum morphology
0000190
Aortic dissection
Tear in inner wall of large artery that carries blood away from heart
0002647
Aplasia/Hypoplasia of the earlobes
Absent/small ear lobes
Absent/underdeveloped ear lobes

[ more ]

0009906
Aplasia/Hypoplasia of the eyebrow
Absence of eyebrow
Lack of eyebrow
Missing eyebrow

[ more ]

0100840
Bladder diverticulum
0000015
Bruising susceptibility
Bruise easily
Easy bruisability
Easy bruising

[ more ]

0000978
Carious teeth
Dental cavities
Tooth cavities
Tooth decay

[ more ]

0000670
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Dermal translucency
0010648
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
Gastrointestinal infarctions
Death of digestive organ tissue due to poor blood supply
0005244
Global developmental delay
0001263
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Hypokalemia
Low blood potassium levels
0002900
Internal hemorrhage
Internal bleeding
0011029
Macule
Flat, discolored area of skin
0012733
Melanocytic nevus
Beauty mark
0000995
Mitral valve prolapse
0001634
Pectus excavatum
Funnel chest
0000767
Peripheral arteriovenous fistula
0100784
Pneumothorax
Collapsed lung
0002107
Protruding ear
Prominent ear
Prominent ears

[ more ]

0000411
Short stature
Decreased body height
Small stature

[ more ]

0004322
Sprengel anomaly
High shoulder blade
0000912
Telecanthus
Corners of eye widely separated
0000506
Thin skin
0000963
30%-79% of people have these symptoms
Arterial dissection
0005294
Arteriovenous fistulas of celiac and mesenteric vessels
0002642
Flat face
Flat facial shape
0012368
Glaucoma
0000501
Premature birth
Premature delivery of affected infants
Preterm delivery

[ more ]

0001622
Proptosis
Bulging eye
Eyeballs bulging out
Prominent eyes
Prominent globes
Protruding eyes

[ more ]

0000520
Respiratory insufficiency
Respiratory impairment
0002093
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot

[ more ]

0001762
Telangiectasia of the skin
0100585
Thin vermilion border
Decreased volume of lip
Thin lips

[ more ]

0000233
Varicose veins
0002619
5%-29% of people have these symptoms
Abnormal intestine morphology
Abnormality of the intestine
0002242
Abnormal pupil morphology
Abnormality of the pupil
Pupillary abnormalities
Pupillary abnormality

[ more ]

0000615
Abnormality of hair texture
0010719
Alopecia
Hair loss
0001596
Aplasia/Hypoplasia of the abdominal wall musculature
Absent/small abdominal wall muscles
Absent/underdeveloped abdominal wall muscles

[ more ]

0010318
Ascending tubular aorta aneurysm
Bulging of wall of large artery located above heart
0004970
Blue sclerae
Whites of eyes are a bluish-gray color
0000592
Cigarette-paper scars
'cigarette paper scarring'
Cigarette paper scarring

[ more ]

0001073
Congenital hip dislocation
Dislocated hip since birth
0001374
Cystocele
Bladder hernia
Dropped bladder

[ more ]

0100645
Deeply set eye
Deep set eye
Deep-set eyes
Sunken eye

[ more ]

0000490
Excessive wrinkled skin
0007392
Gingival overgrowth
Gum enlargement
0000212
Gingivitis
Inflamed gums
Red and swollen gums

[ more ]

0000230
Hemoptysis
Coughing up blood
0002105
High, narrow palate
Narrow, high-arched roof of mouth
Narrow, highly arched roof of mouth

[ more ]

Cause

Vascular Ehlers-Danlos syndrome is typically caused by a change (mutation) in the COL3A1 gene. Rarely, it may be caused by a mutation in the COL1A1 gene.[3]

The COL3A1 gene provides instructions for making a component of type III collagen. Collagen is a protein that provides structure and strength to connective tissues throughout the body. Type III collagen, specifically, is found in tissues such as the skin, lungs, intestinal walls, and the walls of blood vessels. Mutations in the COL3A1 gene lead to defects in type III collagen and/or reduced amounts of type III collagen. This causes the many signs and symptoms associated with vascular EDS.[5] The COL1A1 gene provides instructions for making part of type I collagen. Type I collagen is the most abundant form of collagen in the human body.[6]

Diagnosis

A diagnosis of vascular Ehlers-Danlos syndrome is typically based on the presence of characteristic signs and symptoms. Genetic testing for a change (mutation) in the COL3A1 gene (usually) or the COL1A1 gene (rarely) can be ordered to confirm the diagnosis.[1][2]

Collagen typing performed on a skin biopsy may be recommended if genetic testing is inconclusive. Collagen is a tough, fiber-like protein that makes up about a third of body protein. It is part of the structure of tendons, bones, and connective tissues. People with vascular EDS typically have abnormalities in type III collagen.[1][2]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    The treatment and management of vascular Ehlers-Danlos syndrome (EDS) aims to relieve signs and symptoms and prevent serious complications. For example, people with vascular EDS have tissue fragility that puts them at high risk for rupturing of arteries, muscles and internal organs. It is therefore important to seek immediate medical attention for any sudden, unexplained pain because emergency surgery may be needed. Pregnant women with vascular EDS should be followed by a maternal-fetal medicine specialist at a center for high-risk pregnancies.[4][2]

    Periodic screening may be recommended to diagnose aneurysms or other problems that may not cause obvious symptoms. The risk of injury should be minimized by avoiding contact sports, heavy lifting, and weight training. Elective surgery is also discouraged.[2]

    GeneReview's Web site offers more specific information about the treatment and management of vascular EDS. Please click on the link to access this resource.

    Please speak to your healthcare provider if you have any questions about your personal medical management plan.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Social Networking Websites

      • The Ehlers-Danlos, Marfan and Related CTDs New England/MA Facebook Support Group offers educational and peer support through this forum.
      • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
        • Genetics Home Reference (GHR) contains information on Vascular Ehlers-Danlos syndrome. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
            Ehlers-Danlos Syndrome
            Genetics of Ehlers-Danlos Syndrome
          • MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Vascular Ehlers-Danlos syndrome. Click on the link to view a sample search on this topic.

            References

            1. Pauker SP & Stoler J. Clinical manifestations and diagnosis of Ehlers-Danlos syndromes. UpToDate. February 22, 2016; https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-ehlers-danlos-syndromes.
            2. Melanie G Pepin, MS, CGC and Peter H Byers, MD. Ehlers-Danlos Syndrome Type IV. GeneReviews. May 2011; https://www.ncbi.nlm.nih.gov/books/NBK1494/.
            3. Malfait F, Francomano C, Byers P et al. The 2017 international classification of the Ehlers–Danlos syndromes. Am J Med Genet C Semin Med Genet. March, 2017; 175(1):8-26. https://onlinelibrary.wiley.com/doi/10.1002/ajmg.c.31552/full.
            4. Pauker SP & Stoler J. Overview of the management of Ehlers-Danlos syndromes. UpToDate. 2016; https://www.uptodate.com/contents/overview-of-the-management-of-ehlers-danlos-syndromes.
            5. COL3A1. Genetics Home Reference. May 2006; https://ghr.nlm.nih.gov/gene/COL3A1.
            6. COL1A1. Genetics Home Reference. April 2013; https://ghr.nlm.nih.gov/gene/COL1A1.

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