Vascular Ehlers-Danlos syndrome

Alternate names

Ehlers Danlos syndrome, ecchymotic type; Ehlers Danlos syndrome, arterial type; Ehlers Danlos syndrome, Sack-Barabas type; EDS4 (formerly); Ehlers-Danlos syndrome type 4 (formerly); EDS IV (formerly); EDS type 4 (formerly); Ehlers-Danlos syndrome type IV (formerly); Sack-Barabas syndrome; EDS IV; EDS type 4; Ehlers-Danlos syndrome type 4; Ehlers-Danlos syndrome type IV; Arterial-ecchymotic EDS; Ehlers-Danlos syndrome, vascular type; Vascular EDS; vEDS

Definition

Ehlers-Danlos syndrome is a group of disorders that affect connective tissues supporting the skin, bones, blood vessels, and many other organs and tissues. Defects in connective tissues cause the signs and symptoms of these conditions, which range from mildly loose joints to life-threatening complications.

Types

The various forms of Ehlers-Danlos syndrome have been classified in several different ways. Originally, 11 forms of Ehlers-Danlos syndrome were named using Roman numerals to indicate the types (type I, type II, and so on). In 1997, researchers proposed a simpler classification (the Villefranche nomenclature) that reduced the number of types to six and gave them descriptive names based on their major features. In 2017, the classification was updated to include rare forms of Ehlers-Danlos syndrome that were identified more recently. The 2017 classification describes 13 types of Ehlers-Danlos syndrome.

Epidemiology

The combined prevalence of all types of Ehlers-Danlos syndrome appears to be at least 1 in 5,000 individuals worldwide. The hypermobile and classical forms are most common; the hypermobile type may affect as many as 1 in 5,000 to 20,000 people, while the classical type probably occurs in 1 in 20,000 to 40,000 people. Other forms of Ehlers-Danlos syndrome are rare, often with only a few cases or affected families described in the medical literature.

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.

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. 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.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

Vascular Ehlers-Danlos syndrome is typically inherited in an autosomal dominant manner. This means that to be affected, a person only needs a change (mutation) in one copy of the responsible gene in each cell. In some cases, an affected person inherits the mutation from an affected parent. Other cases may result from new (de novo) mutations in the gene. These cases occur in people with no history of the disorder in their family. A person with vascular EDS has a 50% chance with each pregnancy of passing along the altered gene to his or her child.

Signs and symptoms

The signs and symptoms of vascular Ehlers-Danlos syndrome vary but may include:

• 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

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Abnormal eyelash morphology(Abnormal eyelashes)
• Abnormal oral frenulum morphology
• Aortic dissection(Tear in inner wall of large artery that carries blood away from heart)
• Aplasia/Hypoplasia of the earlobes(Absent/small ear lobes)
• Aplasia/Hypoplasia of the eyebrow(Absence of eyebrow)
• Bladder diverticulum
• Bruising susceptibility(Bruise easily)
• Carious teeth(dental cavities)
• Cognitive impairment(Abnormality of cognition)
• Cryptorchidism(undescended testes)
• Dermal translucency
• EpicanthusEye folds
• Gastrointestinal infarctions(death of digestive organ tissue due to poor blood supply)
• Global developmental delay
• Hypertelorism(Wide-set eyes)
• Hypokalemia(Low blood potassium levels)
• Internal hemorrhage(nternal bleeding)
• Macule(Flat, discolored area of skin)
• Melanocytic nevus(Beauty mark)
• Mitral valve prolapse
• Pectus excavatum(Funnel chest)
• Peripheral arteriovenous fistula
• Pneumothorax(Collapsed lung)
• Protruding ear(Prominent ear)
• Short stature(Decreased body height)
• Sprengel anomaly(High shoulder blade)
• Telecanthus(Corners of eye widely separated)
• Thin skin

30%-79% of people have these symptoms

• Arterial dissection
• Arteriovenous fistulas of celiac and mesenteric vessels
• Flat face(Flat facial shape)
• Glaucoma
• Premature birth(Premature delivery of affected infants)
• Proptosis(Bulging eye)
• Respiratory insufficiency(Respiratory impairment)
• Talipes equinovarus(Club feet)
• Telangiectasia of the skin
• Thin vermilion border(Decreased volume of lip)
• Varicose veins

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.

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.

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. 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.

Prognosis

The long-term outlook (prognosis) for people with vascular Ehlers-Danlos syndrome is generally poor. It is typically considered the most severe form of EDS and is often associated with a shortened lifespan. Among affected people diagnosed as the result of a complication, 25% have experienced a significant medical complication by age 20 and more than 80% by age 40. The median life expectancy for people affected by vascular EDS is 48 years.

NIH genetic and rare disease info

• NIH info on Vascular Ehlers-Danlos syndrome

Vascular Ehlers-Danlos syndrome is a rare disease.

Vascular Ehlers-Danlos syndrome Resources
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