ConditionBones, joints & muscles
Connective Tissue Disorders: Types and How They Differ
Connective tissue disorders are conditions that affect the tissues that support and hold the body together: skin, ligaments, tendons, cartilage, bone and blood vessel walls. They fall into two broad groups. Heritable disorders, such as Ehlers-Danlos syndrome, Marfan syndrome and osteogenesis imperfecta, are caused by gene changes in proteins like collagen and fibrillin. Autoimmune disorders, such as lupus and scleroderma, are caused by the immune system attacking these tissues. Diagnosis and treatment differ greatly between the two.
Also called: Connective tissue diseases, heritable connective tissue disorders, collagen disorders
At a glance
- What they are
- Conditions affecting the body's structural tissues, either inherited or autoimmune.
- Heritable examples
- Ehlers-Danlos syndromes, Marfan syndrome, Loeys-Dietz syndrome, osteogenesis imperfecta, cutis laxa.
- Autoimmune examples
- Lupus, scleroderma, Sjogren's disease, myositis, mixed connective tissue disease.
- Main risks in heritable types
- Aortic aneurysm and dissection, joint dislocations, fractures, eye lens problems.
- Diagnosis
- Clinical criteria, genetic testing, echocardiogram for heritable types; antibody blood tests for autoimmune types.
When to get help
Call 911 or go to the ER
- Sudden severe tearing pain in the chest, back or belly, especially with Marfan, Loeys-Dietz or vascular Ehlers-Danlos syndrome (possible aortic dissection)
- Sudden severe abdominal pain or bleeding in someone with vascular Ehlers-Danlos syndrome (possible artery or bowel rupture)
- Sudden loss of vision, flashes and floaters, or a curtain over vision (possible retinal detachment)
See a doctor within a day or two
- Sudden shortness of breath with chest pain in a tall, thin person (possible collapsed lung)
- Fingers turning black or developing ulcers
- New kidney swelling, foamy urine or chest pain in someone with lupus or scleroderma
Book a routine appointment
- Very flexible joints with frequent dislocations, chronic pain or easy bruising
- Tall stature, long limbs, a chest wall deformity and nearsightedness, or a family history of aortic aneurysm
- Repeated fractures with minor injuries, or blue-tinged whites of the eyes
- Joint pain with rashes, Raynaud phenomenon or dry eyes and mouth
For a detailed guide to autoimmune connective tissue diseases, their symptoms and blood tests, see connective tissue disease (autoimmune).
Heritable vs autoimmune: the key differences
| Heritable | Autoimmune | |
|---|---|---|
| Cause | Gene change in a structural protein | Immune system attacks tissues |
| Onset | Present from birth; signs may appear in childhood or later | Usually adulthood, often 20s to 50s |
| Family history | Often, though new mutations occur | Sometimes; risk partly inherited |
| Typical problems | Loose joints, fragile skin, aortic enlargement, fractures, lens dislocation | Inflammation: joint pain, rashes, organ inflammation |
| Tests | Clinical criteria, genetic testing, echocardiogram | ANA and specific antibodies, inflammatory markers |
| Treatment | Monitoring, preventing complications, surgery | Immune-modifying medicines |
Heritable connective tissue disorders
Ehlers-Danlos syndromes (EDS)
A group of 13 types affecting collagen. Ehlers-Danlos syndrome features joint hypermobility, stretchy or fragile skin, easy bruising and poor wound healing.
- Hypermobile EDS is the most common type. It causes joint instability, subluxations, chronic pain and fatigue. No single gene has been identified, so diagnosis is clinical.
- Classical EDS has more marked skin fragility and wide scars.
- Vascular EDS is rarer but serious, with fragile arteries, bowel and uterus, and a risk of rupture. Thin, translucent skin and extensive bruising are clues.
See also joint hypermobility.
Marfan syndrome
Marfan syndrome is caused by changes in the FBN1 (fibrillin-1) gene. Features include:
- tall stature with long arms, legs and fingers
- chest wall deformity (sunken or protruding breastbone) and scoliosis
- dislocated eye lenses and severe nearsightedness
- enlargement of the aortic root, which can lead to dissection
Loeys-Dietz syndrome
Loeys-Dietz syndrome causes aggressive aneurysms throughout the arterial tree, widely spaced eyes, a split uvula and twisted arteries. Aneurysms can dissect at smaller sizes than in Marfan syndrome.
Osteogenesis imperfecta
Osteogenesis imperfecta ("brittle bone disease") causes bones that fracture easily, often with blue-gray whites of the eyes, hearing loss and short stature.
Other heritable disorders
- Cutis laxa: loose, sagging skin, sometimes with lung and vessel problems
- Stickler syndrome: joint, eye (high myopia, retinal detachment) and hearing problems
- Pseudoxanthoma elasticum: yellowish skin papules, eye and vessel problems
Autoimmune connective tissue diseases
These include systemic lupus erythematosus, scleroderma, Sjogren's disease, dermatomyositis and polymyositis, and mixed connective tissue disease. They cause inflammation in many organs, with joint pain, fatigue, rashes, Raynaud phenomenon and dryness. They are covered in detail on the autoimmune page linked above.
Diagnosis of heritable disorders
- Clinical criteria: for example, the Ghent criteria for Marfan syndrome and the 2017 EDS criteria for hypermobile EDS.
- Beighton score: a 9-point test of joint flexibility.
- Genetic testing: confirms most types other than hypermobile EDS.
- Echocardiogram and other imaging: measure the aortic root and look for aneurysms; CT or MRI angiography for Loeys-Dietz and vascular EDS.
- Eye examination: slit-lamp exam for lens dislocation.
Relatives may be offered screening once a diagnosis is made.
Management of heritable disorders
There is no cure, but complications can be reduced:
- regular imaging of the aorta, and medicines such as beta blockers or angiotensin receptor blockers to slow aortic enlargement
- preventive aortic surgery when the aorta reaches a set size
- physical therapy to strengthen muscles around loose joints
- pain management, including approaches for chronic pain and fatigue in hypermobile EDS
- bisphosphonates and fracture care in osteogenesis imperfecta
- activity advice: avoiding heavy lifting, intense isometric exercise and contact sports in vascular conditions
- pregnancy planning, since pregnancy carries higher aortic and uterine risks in some types
Frequently asked questions
What are connective tissue disorders?
They are conditions affecting the tissues that support the body, such as skin, ligaments, cartilage, bones and blood vessels. Some are inherited, like Ehlers-Danlos and Marfan syndromes, and others are autoimmune, like lupus and scleroderma.
What is the difference between Ehlers-Danlos and Marfan syndrome?
Ehlers-Danlos syndromes mainly cause joint hypermobility and stretchy, fragile skin, from collagen problems. Marfan syndrome, from a fibrillin-1 gene change, causes tall stature, long limbs, lens dislocation and aortic enlargement. Both can affect joints and blood vessels.
Are connective tissue disorders genetic?
Heritable connective tissue disorders are genetic, caused by changes in genes for structural proteins, and often run in families. Autoimmune connective tissue diseases are not directly inherited, though genetic factors increase susceptibility.
How are connective tissue disorders diagnosed?
Heritable disorders are diagnosed with clinical criteria, genetic testing and imaging such as an echocardiogram. Autoimmune disorders are diagnosed with symptoms, examination and blood tests such as ANA and specific antibodies, plus organ tests.
Sources
This guide was written from current patient and clinical guidance, including:
- MedlinePlus Genetics: Ehlers-Danlos syndrome; Marfan syndrome; Loeys-Dietz syndrome
- The Ehlers-Danlos Society: 2017 International Classification of the Ehlers-Danlos Syndromes
- The Marfan Foundation: What is Marfan syndrome?
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): Heritable Disorders of Connective Tissue
- American College of Rheumatology: Patient fact sheets