Classical Ehlers-Danlos syndrome

Other Names: Classic Ehlers-Danlos syndrome; Ehlers-Danlos syndrome type 1 (formerly); Ehlers-Danlos syndrome type 2 (formerly); Ehlers-Danlos syndrome, classic type

Classical Ehlers-Danlos syndrome (EDS) is a genetic connective tissue disorder that is caused by defects in a protein called collagen. Common symptoms include skin hyperextensibility, abnormal wound healing, and joint hypermobility.

Cause

More than 90% of people affected by classical EDS have an identifiable mutation in the COL5A1 gene or the COL5A2 gene that is known to cause the condition. These genes provide instructions for making different components of type V collagen. Collagen is a protein that provides structure and strength to connective tissues throughout the body. Mutations in COL5A1 or COL5A2 lead to defects in the structure and function of type V collagen molecules. This causes the many signs and symptoms associated with classical EDS.

In rare cases, mutations in the genes encoding type I collagen (COL1A1 gene) can be found in people with classical EDS.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

Classical EDS is inherited in an autosomal dominant manner.This means that to have the syndrome, a person needs a mutation in only one copy of the known disease-causing genes in each cell. In some cases, a person with classical EDS inherits the mutation from a parent with the syndrome. 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 classical EDS has a 50% chance with each pregnancy of passing along the mutated gene to his or her child.

Signs and symptoms

The signs and symptoms of classical EDS vary but may include:

• Smooth, velvety skin that is highly elastic (stretchy) and bruises easily
• Abnormal wound healing that may result in wide, atrophic scars (flat and/or depressed scars)
• Joint hypermobility that leads to frequent dislocations and subluxations (partial dislocations)
• Molluscoid pseudotumors (calcified hematomas over pressure points such as the elbow)
• Subcutaneous spheroids (fat-containing cysts that are often found on the forearms and/or shins)
• Hypotonia
• Delayed motor development
• Tissue fragility that may lead to hernias, rectal prolapse, and other complications
• Cardiovascular abnormalities such as mitral valve prolapse or aortic root dilatation (enlargement of the blood vessel that distributes blood from the heart to the rest of the body)
• Pregnancy may be complicated by premature rupture of membranes

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

• Cigarette-paper scars('cigarette paper scarring')
• Fragile skin(Skin fragility)
• Generalized joint laxity(Hypermobility of all joints)
• Hyperextensible skin(Hyperelastic skin)
• Soft, doughy skin
• Striae distensae(Stretch marks)

30%-79% of people have these symptoms

• Chronic constipation(Infrequent bowel movements)
• Fatigue(Tired)
• Gastroesophageal reflux(Acid reflux)
• Muscle spasm
• Muscle weakness(Muscular weakness)
• Muscular hypotonia(Low or weak muscle tone)
• Nausea
• Osteopenia
• Poor wound healing
• Pulp stones
• Vomiting(Throwing up)

5%-29% of people have these symptoms

• Abnormal cornea morphology
• Abnormality of the temporomandibular joint(Abnormality of the jaw joint)
• Acrocyanosis(Persistent blue color of hands, feet, or parts of face)
• Aortic root aneurysm(Bulge in wall of root of large artery that carries blood away from heart)
• Arterial dissection
• Arterial rupture
• Arteriovenous fistula
• Arthralgia(Joint pain)
• Bladder diverticulum
• Blepharochalasis
• Bruising susceptibility(Bruise easily)
• Cervical insufficiency
• Dermatochalasis(Baggy eyes)
• Dilatation of the cerebral artery
• Dislocated radial head
• Ecchymosis
• Epicanthus(Eye folds)
• Hiatus hernia(Stomach hernia)
• Hip dislocation(Dislocated hips)
• Incisional hernia
• Inguinal hernia
• Joint swelling
• Limb pain
• Molluscoid pseudotumors
• Motor delay
• Osteoarthritis(Degenerative joint disease)
• Patellar dislocation(Dislocated kneecap)
• Pes planus(Flat feet)
• Phalangeal dislocation
• Piezogenic pedal papules
• Premature birth(Premature delivery of affected infants)
• Premature rupture of membranes
• Prematurely aged appearance(Precociously senile appearance)
• Prolonged bleeding time
• Rectal prolapse(Rectum protrudes through anus)
• Scoliosis
• Shoulder dislocation
• Subcutaneous spheroids
• Talipes equinovarus(Club feet)
• Umbilical hernia
• Uterine prolapse(Sagging uterus)

Diagnosis

A diagnosis of classical EDS is typically based on the presence of characteristic signs and symptoms. More than 90% of classical EDS patients have mutations in one of the genes encoding type V collagen (the COL5A1 gene or the COL5A2 gene). Rare cases are caused by a mutation in the COL1A1 gene. Genetic testing for a mutation in these genes can then be ordered to confirm the diagnosis in some cases.

Collagen typing performed on a skin biopsy may be recommended if genetic testing is not available or inconclusive. Transmission electron microscopy (TEM) (a very powerful microscopy) findings of collagen flowers on skin biopsy can support the clinical diagnosis, but cannot confirm it. 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. Although this test is generally not helpful in confirming a diagnosis of classical EDS, it can be used to rule out some of the other forms of EDS.

Absence of these findings does not rule-out the diagnosis of classical EDS; however, alternative diagnoses should be considered in the absence of a type V collagen gene mutation or electron microscopy findings.

Treatment

The treatment of classical EDS varies based on the signs and symptoms present in each person. For example, children with hypotonia and/or delayed motor milestones may benefit from physical therapy and occupational therapy. These treatments can also help improve joint stability.

Assistive devices such as braces may also be necessary depending on the severity of joint instability. Anti-inflammatory medications may be prescribed for joint pain. Because classical EDS is associated with fragile skin with abnormal wound healing, people with the syndrome, especially children, may need to wear protective bandages or pads over exposed areas, such as the knees, shins, and forehead. Children and adolescents may be monitored for the development of aortic root dilatation (enlargement of the blood vessel that distributes blood from the heart to the rest of the body).

NIH genetic and rare disease info

• NIH info on Classical Ehlers-Danlos syndrome

Classical Ehlers-Danlos syndrome is a rare disease.

Classical Ehlers-Danlos syndrome Resources
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