Studies of Heritable Disorders of Connective Tissue
| Status: | Completed |
|---|---|
| Conditions: | Arthritis, Other Indications, Neurology, Orthopedic, Women's Studies |
| Therapuetic Areas: | Neurology, Rheumatology, Orthopedics / Podiatry, Other, Reproductive |
| Healthy: | No |
| Age Range: | 2 - Any |
| Updated: | 4/17/2018 |
| Start Date: | January 21, 2003 |
| End Date: | January 2, 2015 |
Clinical and Molecular Manifestations of Heritable Disorders of Connective Tissue
Background:
- Heritable disorders of connective tissue are genetic conditions that can affect the skin
and other parts of the body. They are related to mutations in genes that are responsible for
building tissues. The symptoms differ among disorders. Researchers want to study which genes
may be responsible for different disorders. They will be performing a long-term (up to 10
years) study and a study that requires a single visit. These studies will look at how these
disorders affect the body and what genes may cause these conditions.
Objectives:
- To perform one-time and long-term studies of people who have heritable disorders of
connective tissue.
Eligibility:
- Individuals at least 2 years of age who have or may have a heritable disorder of connective
tissue.
Design:
- Participants will be screened with a physical exam, medical history, and blood samples.
- Participants will be on one of two parts of this study. The longitudinal arm will
require long-term study over about 10 years. The mutational analysis arm will involve a
single visit.
- Longitudinal arm participants must be at least 12 years of age. They will have study
visits at regular intervals for up to 10 years. The tests given at these visits may
include all or some of the following:
- Blood, saliva, urine, and skin samples
- Heart and lung function tests
- Magnetic resonance imaging scans of the neck, chest, spine, and abdomen
- Other imaging studies such as x-rays, bone density scans, and ultrasounds
- Questionnaires about sleep, pain, and quality of life
- Photographs of affected areas.
- Mutational analysis arm participants will have a single study visit. They will provide
blood and saliva samples. They will provide tissue from a skin biopsy. They will also
let the researchers take photos of any affected body parts. They will complete
questionnaires about sleep, pain, and quality of life.
- Heritable disorders of connective tissue are genetic conditions that can affect the skin
and other parts of the body. They are related to mutations in genes that are responsible for
building tissues. The symptoms differ among disorders. Researchers want to study which genes
may be responsible for different disorders. They will be performing a long-term (up to 10
years) study and a study that requires a single visit. These studies will look at how these
disorders affect the body and what genes may cause these conditions.
Objectives:
- To perform one-time and long-term studies of people who have heritable disorders of
connective tissue.
Eligibility:
- Individuals at least 2 years of age who have or may have a heritable disorder of connective
tissue.
Design:
- Participants will be screened with a physical exam, medical history, and blood samples.
- Participants will be on one of two parts of this study. The longitudinal arm will
require long-term study over about 10 years. The mutational analysis arm will involve a
single visit.
- Longitudinal arm participants must be at least 12 years of age. They will have study
visits at regular intervals for up to 10 years. The tests given at these visits may
include all or some of the following:
- Blood, saliva, urine, and skin samples
- Heart and lung function tests
- Magnetic resonance imaging scans of the neck, chest, spine, and abdomen
- Other imaging studies such as x-rays, bone density scans, and ultrasounds
- Questionnaires about sleep, pain, and quality of life
- Photographs of affected areas.
- Mutational analysis arm participants will have a single study visit. They will provide
blood and saliva samples. They will provide tissue from a skin biopsy. They will also
let the researchers take photos of any affected body parts. They will complete
questionnaires about sleep, pain, and quality of life.
Heritable disorders of connective tissue are a heterogenous group of genetic conditions
caused by defects of extracellular matrix elements such as collagen, elastin,
mucopolysaccharides or related biomolecules. The genetic cause of many connective tissue
disorders has been elucidated, while others are yet to be discovered or further defined.
While clinical diagnostic criteria have been established for several of the connective tissue
syndromes, many share features that overlap the known descriptions of other connective tissue
disorders. Therefore, further characterization and phenotype/genotype correlation is needed
to adequately diagnose and find treatments for these yet-to-be genotyped disorders.
An aim of this work is the examination of the cardiovascular, musculoskeletal and
neurological complications of heritable connective tissue disorders (HDCT) and the natural
history of these complications. Through mutational analysis for genes known to cause the
HDCT, as well as identification of new genes, we will assess the relationship between
specific mutations and their associated disease phenotypes. Through the analysis of tissue
specimens obtained from patients with HDCT, we will identify the biochemical pathways that
lead to connective tissue fragility. We will continue to assess the severity, prevalence, and
pattern of pain and related psychological and quality of life dimensions in HDCT.
The resulting understanding of genotype/phenotype correlations and biochemical pathways will
enhance our understanding of connective tissue biology. This knowledge has the potential to
lead to new treatments for not only patients with HDCT, but also for pathological conditions
associated with the weakness of connective tissues in aging.
caused by defects of extracellular matrix elements such as collagen, elastin,
mucopolysaccharides or related biomolecules. The genetic cause of many connective tissue
disorders has been elucidated, while others are yet to be discovered or further defined.
While clinical diagnostic criteria have been established for several of the connective tissue
syndromes, many share features that overlap the known descriptions of other connective tissue
disorders. Therefore, further characterization and phenotype/genotype correlation is needed
to adequately diagnose and find treatments for these yet-to-be genotyped disorders.
An aim of this work is the examination of the cardiovascular, musculoskeletal and
neurological complications of heritable connective tissue disorders (HDCT) and the natural
history of these complications. Through mutational analysis for genes known to cause the
HDCT, as well as identification of new genes, we will assess the relationship between
specific mutations and their associated disease phenotypes. Through the analysis of tissue
specimens obtained from patients with HDCT, we will identify the biochemical pathways that
lead to connective tissue fragility. We will continue to assess the severity, prevalence, and
pattern of pain and related psychological and quality of life dimensions in HDCT.
The resulting understanding of genotype/phenotype correlations and biochemical pathways will
enhance our understanding of connective tissue biology. This knowledge has the potential to
lead to new treatments for not only patients with HDCT, but also for pathological conditions
associated with the weakness of connective tissues in aging.
- INCLUSION CRITERIA:
- Individuals and their family members will be offered enrollment if they have an
established or suspected diagnosis of Marfan, Stickler, or Ehlers-Danlos syndrome, or
Overlap connective tissue disorder.
- Determination of eligibility will be made by review of prior records.
- In some cases, a screening evaluation to establish the diagnosis may be performed
subjects may be excluded from further participation if the diagnosis is ruled out.
Cytogenetic analysis may be necessary to rule out a chromosomal abnormality that has
overlapping features with HDCT.
- Clinical inclusion criteria require: 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 bruising and/or hyperextensibile skin, pectus excavatum or carinatum, scoliosis,
spondylolisthesis and/or dural ectasia, Chiari I Malformation, high frequency
sensorineural hearing loss, fibromuscular dysplasia of arteries, aneurysms.
EXCLUSION CRITERIA:
- The only exclusion criterion is inability to provide informed consent, or the absence
of a guardian who is authorized to provide informed consent in the case of minor
subjects.
- There will be no exclusion based upon age, gender, ethnicity, socioeconomic status, or
any other factor except ability 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.
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