Ehlers-Danlos syndromes are hereditary collagen disorders characterized by joint hypermobility, dermal hyperelasticity, and widespread tissue fragility. Diagnosis is clinical. Treatment is supportive.
Inheritance is usually autosomal dominant, but Ehlers-Danlos syndromes are heterogeneous. Different gene mutations affect the amount, structure, or assembly of different collagens. Mutations can exist in the genes that encode different types of collagen (eg, type I, III, or V) or collagen-modifying enzymes (eg, lysyl hydroxylase, a collagen-cleaving protease).
There are 6 major types:
Hypermobile
Classic
Vascular
Kyphoscoliosis
Arthrochalasia
Dermatosparaxis
Hypermobile, classic, and vascular types are the most common.
There are also 7 rare types.
Symptoms and Signs of Ehlers-Danlos Syndromes
Symptoms and signs of Ehlers-Danlos syndromes vary widely, but certain manifestations are considered characteristic of different types.
Predominant symptoms include hypermobile joints, abnormal scar formation and wound healing, fragile vessels, and velvety, hyperextensible skin. Skin can be stretched several centimeters but returns to normal when released.
Wide papyraceous scars often overlie bony prominences, particularly elbows, knees, and shins; scarring is less severe in the hypermobile type. Molluscoid pseudotumors (fleshy outgrowths) frequently form on top of scars or at pressure points.
Extent of joint hypermobility varies but may be marked in the arthrochalasis, classic, and hypermobile types.
Bleeding tendency is rare, although the vascular type is characterized by vascular rupture and bruising.
Subcutaneous calcified spherules may be palpated or seen on x-rays.
Ускладнення синдромів Елерса-Данлоса
Minor trauma may cause wide gaping wounds but little bleeding; surgical wound closure may be difficult because sutures tend to tear out of the fragile tissue. Surgical complications occur because of deep tissue fragility.
Sclera may be fragile, leading to perforation of the globe in the kyphoscoliosis type.
Bland synovial effusions, sprains, and dislocations occur frequently. Spinal kyphoscoliosis occurs in 25% of patients (especially in those with the kyphoscoliosis type), thoracic deformity in 20%, and talipes equinovarus in 5%. About 90% of affected adults have pes planus (flat feet). Developmental dysplasia of the hip (formerly congenital dislocation of the hip) occurs in 1%; the arthrochalasis type is characterized by bilateral developmental dysplasia of the hip.
Gastrointestinal (GI) hernias and diverticula are common. Rarely, portions of the GI tract spontaneously hemorrhage and perforate, and dissecting aortic aneurysm and large arteries spontaneously rupture.
Valvular prolapse is a common complication in the most severe type (vascular type).
In pregnant women, tissue extensibility may cause premature birth, cervical incompetence, and possibly uterine rupture; if the fetus is affected, fetal membrane is fragile, sometimes resulting in early rupture. Maternal tissue fragility may complicate episiotomy or cesarean delivery. Antenatal, perinatal, and postnatal bleeding may occur.
Other potentially serious complications include arteriovenous fistula, ruptured viscus, and pneumothorax or pneumohemothorax.
Diagnosis of Ehlers-Danlos Syndromes
Clinical criteria
Confirmatory genetic testing
Echocardiography and/or other vascular imaging to screen for cardiovascular complications
Most but not all types of Ehlers-Danlos syndrome involve one or both of the following:
Joint hypermobility
Skin hyperextensibility
Thus, diagnosis of Ehlers-Danlos syndromes may be suspected in patients who present with complaints such as frequent joint dislocations, poor wound healing, and/or frequent or unusual scarring. However, joint hypermobility is common among the general population. Also, other connective tissue disorders with similar joint and/or skin manifestations (eg, Marfan syndrome, cutis laxa) should be considered.
Screening patients with simple questions regarding joint hypermobility may be helpful (1):
Can you now, or could you ever, place your hands flat on the floor without bending your knees?
Can you now, or could you ever, bend your thumb to touch your forearm?
As a child, did you amuse your friends by contorting your body into strange shapes or could you do the splits?
As a child or teenager, did your kneecap or shoulder dislocate on more than one occasion?
Do you consider yourself “double-jointed”?
A positive answer on 2 or more of these questions strongly suggests hypermobility, which can be further assessed by physical examination using the Beighton scoring system. This tool assesses hypermobility in 4 pairs of joints (5th fingers, thumbs, elbows, knees) and the spine. One point is scored for each joint manifesting the defined hypermobility criterion; a score ≥ 5 is considered to indicate hypermobility (2).
Skin hyperextensibility is assessed in standardized areas. Skin is considered hyperextensible if it can be stretched > 1.5 cm on the distal forearm and dorsum of the hands, > 3 cm on the neck, elbow, and knees, and > 1 cm on the palm (2).
There are major and minor clinical criteria for each Ehlers-Danlos type (2), typically including presence or absence of joint hypermobility and skin hyperextensibility. However, there is much variability both within and among the different types, and diagnosis should be confirmed by genetic testing, which is now available for most subtypes.
Ultrastructural examination of skin biopsy can help in diagnosing the classic, hypermobile, and vascular types.
Echocardiography and other vascular imaging are done to check for heart disorders (eg, valvular prolapse, arterial aneurysm) that are associated with some of the types.
Довідкові матеріали щодо діагностики
1. Hakim AJ, Grahame R: A simple questionnaire to detect hypermobility: An adjunct to the assessment of patients with diffuse musculoskeletal pain. Int J Clin Pract 57(3):163–166, 2003. PMID: 12723715
2. The Ehlers-Danlos Society: EDS types: 2017 International Diagnostic Criteria. Accessed 10/11/2022.
Prognosis for Ehlers-Danlos Syndromes
Life span is usually normal with most types.
Potentially lethal complications occur in certain types (eg, arterial rupture in the vascular type).
Treatment of Ehlers-Danlos Syndromes
Early recognition and treatment of complications
There is no specific treatment for Ehlers-Danlos syndromes.
Trauma should be minimized. Protective clothing and padding may help.
If surgery is done, hemostasis must be meticulous. Wounds are carefully sutured, and tissue tension is avoided.
Obstetric supervision during pregnancy and delivery is mandatory. Genetic counseling should be provided.
Ключові моменти
Ehlers-Danlos syndromes are genetic disorders of connective tissue with 13 identified clinical types.
Patients typically have hypermobile joints, hyperextensible skin, and/or fragile skin and connective tissue.
Fragile connective tissue may predispose cardiac valvular regurgitation, scleral rupture, arterial dissection or rupture, uterine rupture, and other complications.
Diagnosis is made using clinical criteria and typically confirmed by genetic testing.
Додаткова інформація
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
Beighton scoring system for assessing joint hypermobility in Ehlers-Danlos syndrome
American Journal of Medical Genetics Part C: Seminars in Medical Genetics: The 2017 EDS Classification
