Manifestations of Heritable Disorders of Connective Tissue - Full Text View

Sponsor:	National Institute on Aging (NIA)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00270686

Purpose

The purpose of this study is to examine cardiovascular and musculoskeletal complications of heritable connective tissue disorders (HDCT) and the natural history of these complications.

Condition
Ehlers-Danlos Syndrome Marfan Syndrome Stickler Syndrome

Study Type:	Observational
Study Design:	Observational Model: Cohort Time Perspective: Prospective
Official Title:	Clinical and Molecular Manifestations of Heritable Disorders of Connective Tissue

Resource links provided by NLM:

Genetics Home Reference related topics: Ehlers-Danlos syndrome hemophilia Marfan syndrome nonsyndromic deafness Pendred syndrome Stickler syndrome Help Me Understand Genetics

MedlinePlus related topics: Connective Tissue Disorders Ehlers-Danlos Syndrome Marfan Syndrome

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Biospecimen Retention: Samples With DNA

Whole blood, frozen fibroblast cultures from skin or other tissue samples, fixed tissue, plasma

Estimated Enrollment:	300
Study Start Date:	June 2003
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Groups/Cohorts
1 Longitudinal Study Arm: 450 participants who will be involved in extensive testing and will be followed longitudinally. Each participant spends approximately 2 days undergoing clinical evaluations. The clinical visits occur every 1 to 5 years based on the subject's age, medical condition, and ability to travel to the study location.
2 Mutational Analysis Arm: There is an upper limit of 1385 participants for this arm. Participants may come to the NIA Clinical Research Unit for a one-time visit (less than one day in length), or they may enroll off-site by sending in bloods, saliva, or bucca samples for the DNA analysis.
3 Genome Protocol Arm: This arm consists of participants who have been previously enrolled under NHGRI protocol 97-HG-0089, presently inactive. The samples are housed at NIA facilities for use by the PI and collaborators approved by the NIA IRB.

Detailed Description:

The purpose of this research is to investigate a group of genetic disorders called the Hereditary Disorders of Connective Tissue and describe the health problems associated with these conditions. These disorders and their prominent symptoms include:

Marfan Syndrome--vascular dilatation (enlargement) and dissection (a tear in the lining), skeletal abnormalities
Ehlers-Danlos Syndrome--soft fragile skin, bleeding problems, joint laxity (looseness), chronic pain
Stickler Syndrome--premature osteoarthritis, bifid uvula (a split in the fleshy lobe hanging down from the soft palate), cleft palate, hearing loss, vitreoretinal degeneration (degeneration of the retina and the transparent gel that fills the inner portion of the eyeball between the lens and the retina)

People who have a known or strongly suspected diagnosis are eligible to participate. At the NIA Clinical Research Unit which located on the 5th floor at Harbor Hospital, a study investigator will obtain a detailed medical history and perform a physical examination on participants. These evaluations will occur every 2 years for 5 years. Additional studies may include an echocardiogram, ECG, Holter study, bone densitometry, blood and urine tests, magnetic resonance imaging (MRI)/MRA studies and vascular studies. A skin biopsy may be done with a separate consent for some participants. Questionnaires about pain and quality of life will be completed by participants.

Eligibility

Ages Eligible for Study:	12 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

Participants may be self-referred or referred by physician, nurses, genetic counselors, or other health professionals, support groups, and family members. With the exception of male and minority participants we are not actively recruiting new research participants because the number of self-referrals through support groups and enrolled family members have been sufficient.

Criteria

Inclusion Criteria:

Established or strongly suspected diagnosis of Ehlers-Danlos, Marfan, or Stickler syndrome within immediate family
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 (unusually long limbs and digits, deformation of the chest wall), aortic dilatation and/or dissection (a large vessel that comes out of the heart), aneurysms (balloon shaped enlargements) in other vessels, ectopia lentis (dislocation of the lens of the eye), detached retina (separation of the retina from the eyeball), vitreous degeneration (degeneration of the gel that fills the eye) and/or early onset high myopia (near-sightedness), cleft palate, joint laxity and/or dislocation, premature osteoarthritis, skin fragility, striae (stretch marks), easy bruising, and/or hyperextensible skin, scoliosis (curvature of the spine), spondylolisthesis (slippage of the bones of the spine) and/or dural ectasia (distortion of the lining of the spinal cord), high frequency sensorineural hearing loss (inability to hear certain sounds due to nerve impairment)

Exclusion Criteria:

Inability to provide informed consent
Pregnant and nursing women may be limited in their participation in some aspects of the study (e.g. ionizing radiation exposure or MRI) during the time that they are pregnant or nursing

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00270686

Contacts

Contact: NIA Recruiter

410-350-3941

NIAStudiesRecruitment@mail.nih.gov

Locations

United States, Maryland
NIA Clinical Research Unit located at Harbor Hospital	Recruiting
Baltimore, Maryland, United States, 21225
Contact: Leslie Sloper, RN 410-350-7391 sloperlj@mail.nih.gov
Principal Investigator: Nazli McDonnell, MD, PhD

Sponsors and Collaborators

National Institute on Aging (NIA)

Investigators

Principal Investigator:

Nazli McDonnell, MD, PhD

National Institute on Aging (NIA)

More Information

Publications:

McDonnell NB, Gorman BL, Mandel KW, Schurman SH, Assanah-Carroll A, Mayer SA, Najjar SS, Francomano CA. Echocardiographic findings in classical and hypermobile Ehlers-Danlos syndromes. Am J Med Genet A. 2006 Jan 15;140(2):129-36.

Milhorat TH, Bolognese PA, Nishikawa M, McDonnell NB, Francomano CA. Syndrome of occipitoatlantoaxial hypermobility, cranial settling, and chiari malformation type I in patients with hereditary disorders of connective tissue. J Neurosurg Spine. 2007 Dec;7(6):601-9.

Milhorat TH, Bolognese PA, Nishikawa M, Francomano CA, McDonnell NB, Roonprapunt C, Kula RW. Association of Chiari malformation type I and tethered cord syndrome: preliminary results of sectioning filum terminale. Surg Neurol. 2009 Jul;72(1):20-35. Erratum in: Surg Neurol. 2009 Nov;72(5):556.

Matt P, Schoenhoff F, Habashi J, Holm T, Van Erp C, Loch D, Carlson OD, Griswold BF, Fu Q, De Backer J, Loeys B, Huso DL, McDonnell NB, Van Eyk JE, Dietz HC; GenTAC Consortium. Circulating transforming growth factor-beta in Marfan syndrome. Circulation. 2009 Aug 11;120(6):526-32. Epub 2009 Jul 27.

Brooke BS, Arnaoutakis G, McDonnell NB, Black JH 3rd. Contemporary management of vascular complications associated with Ehlers-Danlos syndrome. J Vasc Surg. 2010 Jan;51(1):131-8; discussion 138-9. Epub 2009 Oct 30.

Chen W, Kim MS, Shanbhag S, Arai A, VanRyzin C, McDonnell NB, Merke DP. The phenotypic spectrum of contiguous deletion of CYP21A2 and tenascin XB: quadricuspid aortic valve and other midline defects. Am J Med Genet A. 2009 Dec;149A(12):2803-8.

McDonnell NB. Hereditary Disorders of Connective Tissue. Maryland Family Doctor. Volume 45, No. 1 Summer 2008, 16-17.

Ainsworth SR, Aulicino PL. A survey of patients with Ehlers-Danlos syndrome. Clin Orthop. 1993 Jan;(286):250-6.

Beighton P, de Paepe A, Danks D, Finidori G, Gedde-Dahl T, Goodman R, Hall JG, Hollister DW, Horton W, McKusick VA, et al. International Nosology of Heritable Disorders of Connective Tissue, Berlin, 1986. Am J Med Genet. 1988 Mar;29(3):581-94. No abstract available.

Dietz HC, Pyeritz RE, Hall BD, Cadle RG, Hamosh A, Schwartz J, Meyers DA, Francomano CA. The Marfan syndrome locus: confirmation of assignment to chromosome 15 and identification of tightly linked markers at 15q15-q21.3. Genomics. 1991 Feb;9(2):355-61.

Dietz HC, Cutting GR, Pyeritz RE, Maslen CL, Sakai LY, Corson GM, Puffenberger EG, Hamosh A, Nanthakumar EJ, Curristin SM, et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 1991 Jul 25;352(6333):337-9.

Francomano CA, Liberfarb RM, Hirose T, Maumenee IH, Streeten EA, Meyers DA, Pyeritz RE. The Stickler syndrome: evidence for close linkage to the structural gene for type II collagen. Genomics. 1987 Dec;1(4):293-6.

Francomano CA, Liberfarb RM, Hirose T, Maumenee IH, Streeten EA, Meyers DA, Pyeritz RE. The Stickler syndrome is closely linked to COL2A1, the structural gene for type II collagen. Pathol Immunopathol Res. 1988;7(1-2):104-6. No abstract available.

Matt P, Schoenhoff F, Habashi J, Holm T, Van Erp C, Loch D, Carlson OD, Griswold BF, Fu Q, De Backer J, Loeys B, Huso DL, McDonnell NB, Van Eyk JE, Dietz HC; GenTAC Consortium. Circulating transforming growth factor-beta in Marfan syndrome. Circulation. 2009 Aug 11;120(6):526-32. Epub 2009 Jul 27.

Milhorat TH, Bolognese PA, Nishikawa M, Francomano CA, McDonnell NB, Roonprapunt C, Kula RW. Association of Chiari malformation type I and tethered cord syndrome: preliminary results of sectioning filum terminale. Surg Neurol. 2009 Jul;72(1):20-35. Erratum in: Surg Neurol. 2009 Nov;72(5):556.

Responsible Party:	Nazli McDonnell, M.D., Ph.D. Principle Investigator, National Institute of Aging
ClinicalTrials.gov Identifier:	NCT00270686 History of Changes
Other Study ID Numbers:	AG0060
Study First Received:	December 27, 2005
Last Updated:	October 26, 2010
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

genetics
hereditary disorders
connective tissue

Additional relevant MeSH terms:

Marfan Syndrome
Arachnodactyly
Connective Tissue Diseases
Ehlers-Danlos Syndrome
Genetic Diseases, Inborn
Arthritis
Hearing Loss, Sensorineural
Retinal Detachment
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases

Abnormalities, Multiple
Congenital Abnormalities
Limb Deformities, Congenital
Musculoskeletal Abnormalities
Hemostatic Disorders
Vascular Diseases
Hemorrhagic Disorders
Hematologic Diseases
Skin Abnormalities
Skin Diseases, Genetic
Collagen Diseases
Skin Diseases
Joint Diseases
Hearing Loss
Hearing Disorders

ClinicalTrials.gov processed this record on February 09, 2012