The purposes of this study are to identify the genes responsible for inherited connective
tissue disorders and learn about the range of medical problems they cause. It will
investigate whether specific gene changes cause specific medical problems and will establish
diagnostic criteria (signs and symptoms) for the individual syndromes.
Children and adults with a known or suspected inherited connective tissue disorder (Marfan,
Ehlers-Danlos or Stickler syndrome, or other closely related disorders) and their family
members may be eligible for this study.
Patients enrolled in the study will have a medical history, physical examination and blood
tests, as well as other procedures that may include:
- Echocardiogram (ultrasound of the heart)
- X-rays and other imaging studies, such as magnetic resonance imaging (MRI) or
computerized tomography (CT) scans
- Lung function studies
- Urine tests
- Skin biopsy (removal of a small piece of tissue, under local anesthetic, for
- Examination by various specialists (e.g., in ophthalmology, gastroenterology,
rehabilitation medicine) as needed
- Questionnaires regarding chronic pain and fatigue, quality of life, and the impact of
the connective tissue disorder on the patient and family.
(Patients who wish to enroll but cannot travel to NIH may have a more limited participation,
including review of medical records, telephone interview regarding personal and family
history, and collection of a specimen (blood, skin biopsy, or other) for genetic testing.
Patients will be notified of genetic testing results that show a change responsible for
their connective tissue disorder. If they wish, the information will also be sent to their
local health care provider, along with recommendations for additional tests or treatment
options. No treatment is offered as part of this study.
Participating family members who do not themselves have a connective tissue disorder will
provide a small blood sample for gene testing and be interviewed by telephone about their
personal and family health history. Those whose blood test results show a gene change
associated with a connective tissue disorder will be invited to NIH for a discussion of the
findings or referred to a genetic center in their area.
We will investigate the clinical manifestations and molecular genetic defects of heritable
connective tissue disorders, concentrating on the Marfan, Stickler, and Ehlers-Danlos
syndromes. Although each of these conditions has been known for many years, the full
spectrum of the associated phenotypes continues to be expanded and the genetic etiology of
these conditions has not been completely elucidated. In addition, many patients have
features overlapping two or more of the described syndromes, precluding unequivocal
diagnosis. The goals of this study are to further define and characterize the full
phenotype and natural history of these disorders, and to perform genetic linkage, gene
identification, mutation detection, and genotype/phenotype correlations in affected
individuals and families. Individuals suspected to have Marfan, Stickler or Ehlers-Danlos
syndrome or a closely related disorder, as well as interested family members, will be
enrolled. Participants will undergo genetic analyses and periodic clinical assessment. The
expected outcomes will be improved clinical descriptions of the conditions and gene and
mutation identification with analysis of genotype/phenotype correlations.
Individuals and their family members will be offered enrollment if they have a suspected
or established diagnosis of Marfan, Stickler, Ehlers-Danlos, or a closely related
Personal or family history of one or more of the following features in a pattern
suggestive of a heritable connective tissue disorder:
Marfanoid body habitus;
Aortic dilatation and/or dissection;
Ectopia lentis, detached retina, vitreous degeneration and/or early onset high myopia;
Posterior cleft palate; joint laxity and/or dislocation;
Skin fragility, striae, easy bruisability and/or hyperextensibility;
Pectus excavatum or carinatum;
Scoliosis, spondylolisthesis, and/or dural ectasia;
High frequency sensorineural hearing loss.
Inability to provide informed consent.