Connective Tissue Disease

 What Research Is Being Done on HDCTs?  Heritable Disorders of Connective Tissue

Scientists are working to better understand these disorders at several levels:

(1) to identify the genes in which the mutations reside,

(2) to identify the mutations that result in the clinical condition,

(3) to understand how these mutations result in the condition, and

(4) to use all available information about the condition to plan new therapies and test their use and value, both in animal models and in affected individuals.

Because most of these conditions are uncommon, and individuals with them are widely scattered, it is often difficult to gather information about the clinical course of the disorder and assemble enough people to plan effective clinical trials.


The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health (NIH), is the lead Federal agency for connective tissue research. Several other NIH institutes are also studying HDCTs. NIAMS supports research through grants to scientists around the country, in national and international clinical trials, and at the NIH campus. This is some of the research underway:

NIAMS is conducting an in-depth natural history study of people who have Marfan syndrome (which leads to abnormally long bones), nail-patella syndrome (a congenital skeletal disorder), Stickler syndrome (which causes eye and joint problems), and Ehlers-Danlos syndrome (which causes skin and blood vessel problems). All of these disorders have multiple, interrelated symptoms. NIAMS scientists are closely observing the people in this study over a long period to get a more complete picture of the diseases. They hope to improve their understanding of the genetic origins of the symptoms, of disease progression, and of mutations in patients and their relatives. Scientists expect their findings to apply to other HDCTs as well.

Specific areas of research and findings arising from this long-term study include:

    • examining the efficacy of screening for dural ectasia (an enlargement of the membrane that surrounds the spinal cord) in the diagnosis of Marfan syndrome
    • analyzing the prevalence of spinal and hip abnormalities in Stickler syndrome, and their relationship to chronic pain
    • documenting an increased risk of failure of the femoral head (the ball portion at the top of the thigh bone) in children with Stickler syndrome
    • developing proposed diagnostic criteria for Stickler syndrome based on clinical and molecular studies in this population
    • identifying a connective tissue disorder with features resembling Marfan syndrome, Stickler syndrome, and Ehlers-Danlos syndrome
    • studying the mechanism of chronic musculoskeletal pain in people with HDCTs and exploring ways, including mindfulness-based stress reduction, to ameliorate it
    • looking at some specific musculoskeletal complications of aging in patients with HDCTs, such as the prevalence and severity of osteoporosis and osteoarthritis
    • using molecular genetic studies to identify both new genes contributing to Stickler syndrome and Ehlers-Danlos syndrome, and mutations in previously recognized genes.
  • NIAMS is examining gene defects that lead to abnormal elastin, the connective tissue protein that allows arteries, muscles, and other organs to respond in certain ways to movement. So far, the investigators have shown how elastin gene mutations cause two specific diseases: a skin disease (cutis laxa) and a blood vessel disease (supravalvular aortic stenosis). Scientists hope to learn more about how mutations affect elastin fiber and tissue growth. They also hope to find out how gene defects lead to the development of elastin disease.
  • NIAMS is supporting a study looking for ways to treat diseases such as osteogenesis imperfecta by using gene therapy. Stem cells, which have the potential to develop into more specialized cells, would replace bone cells that have gene defects. This research is being conducted on specially bred mice.
  • NIAMS is encouraging the establishment of new research registries for connective tissue disorders and other conditions. Through these registries, demographic and medical data from patients and families could be collected and used in research on disorders. Epidermolysis bullosa is one of the disorders for which the Institute has already established a research registry.


  • Other NIAMS-supported research pertains to:

    • the chemistry and biology of elastin genes
    • collagen gene defects (several types) that cause bone diseases
    • collagen IV gene defects in mice and humans (Alport syndrome)
    • proteoglycans, a group of proteins that maintain tissue stiffness
    • fibroblasts, cells that form the fibrous tissues in the body
    • cartilage, joints, and skin layers.
  •  Ongoing studies of aneurysms (weak spots in blood vessel walls that threaten to burst) are taking place at several NIH Institutes. Aneurysms can prove deadly to people with Marfan syndrome and other HDCTs. NIAMS has supported these studies by pioneering development of a breed of mice prone to aneurysms. Scientists hope the mutant mice will improve understanding of aneurysms and ways to prevent them.


  • The National Heart, Lung, and Blood Institute supported the 14th Gordon Research Conference on Elastin and Elastic Fibers, which brought together basic scientists and clinicians to exchange data on the makeup of and problems associated with these critical components of connective tissue. The conference produced new insights and stimulated interdisciplinary discussions that could potentially help those living with the more than 200 connective tissue diseases.

  • Studies have shown that the blood pressure medication losartan prevents aortic aneurysms in a mouse model of Marfan syndrome. New studies receiving funding from the National Heart, Lung, and Blood Institute are now underway to determine whether the drug has the same beneficial effect in people.


  • At the National Institute of Child Health and Human Development, scientists are working with young patients who have osteogenesis imperfecta. They hope to learn more about the genetics of the disease and the natural history of the many secondary features involved, as well as rehabilitation techniques. Animal models and human clinical trials are also evaluating the use of bisphosphonates to treat this condition. Bisphosphonates are a group of drugs now used widely to treat osteoporosis.

  • The National Human Genome Research Institute is conducting a clinical study of mind-body therapy for chronic pain in people with Ehlers-Danlos syndrome.

  • The National Eye Institute is supporting research on alterations in the gene that causes pseudoxanthoma elasticum (PXE).

  •  Scientists at the National Institute of Dental and Craniofacial Research are carrying out clinical studies on fibrous dysplasia of bone.
from Ehlers-Danlos National Foundation
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