Study of Heritable Connective Tissue Disorders
Study of Heritable Connective Tissue Disorders
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 microscopic
 examination)

 -  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.
INCLUSION CRITERIA:

 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 syndrome.

 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;

 Premature osteoarthritis;

 Skin fragility, striae, easy bruisability and/or hyperextensibility;

 Pectus excavatum or carinatum;

 Scoliosis, spondylolisthesis, and/or dural ectasia;

 High frequency sensorineural hearing loss.

 EXCLUSION CRITERIA:

 Inability to provide informed consent.