Ignite Creation Date:
2024-05-05 @ 11:40 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00106756
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2005-03-29
Brief Title:
Clinical and Genetic Studies of Familial Exudative Vitreoretinopathy
Sponsor:
National Eye Institute NEI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Familial Exudative Vitreoretinopathy Clinical and Molecular Studies
Status:
COMPLETED
Status Verified Date:
2009-06-26
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will examine the extent of the vision problem in familial exudative vitreoretinopathy FEVR and try to identify the genes responsible for this hereditary eye disorder Patients with FEVR have incomplete formation of blood vessels in the periphery of the retina the inner part of the eye that is responsible for vision As a result abnormal vessels can form and retinal detachment and vitreous bleeding can occur causing significant vision loss Vision loss usually begins in childhood gradually worsening over time Some patients eventually become blind
Patients of all ages with FEVR and their family members may be eligible for this study Participants undergo the following tests and procedures
Family history especially regarding eye disease A family tree is drawn
Blood draw for genetic testing related to FEVR
Eye examination to assess visual acuity eye chart test and eye pressure and to examine pupils lens retina and eye movements The pupils are dilated with drops for this examination
Fluorescein angiography to evaluate the eyes blood vessels A yellow dye is injected into an arm vein and travels to the blood vessels in the eyes Pictures of the retina are taken using a camera that flashes a blue light into the eye The pictures show if any dye has leaked from the vessels into the retina indicating possible blood vessel abnormality
Patients affected with FEVR will also undergo DEXA scan to look for osteoporosis X-rays are used to scan the hip forearm and spine for bone density measurements
Patients of all ages with FEVR and their family members may be eligible for this study Participants undergo the following tests and procedures
Family history especially regarding eye disease A family tree is drawn
Blood draw for genetic testing related to FEVR
Eye examination to assess visual acuity eye chart test and eye pressure and to examine pupils lens retina and eye movements The pupils are dilated with drops for this examination
Fluorescein angiography to evaluate the eyes blood vessels A yellow dye is injected into an arm vein and travels to the blood vessels in the eyes Pictures of the retina are taken using a camera that flashes a blue light into the eye The pictures show if any dye has leaked from the vessels into the retina indicating possible blood vessel abnormality
Patients affected with FEVR will also undergo DEXA scan to look for osteoporosis X-rays are used to scan the hip forearm and spine for bone density measurements
Detailed Description:
Background Familial exudative vitreoretinopathy FEVR is a rare hereditary disorder of the retinal vasculature characterized by abrupt cessation of the growth of peripheral retinal capillaries FEVR seems to exhibit significant phenotypic and genotypic variability but since this is a rare disease the clinical and genetic characteristics of the disease have not been extensively studied so far Correlation of phenotypes with certain genotypes have not been made yet Clinical findings can vary from very mild disease with only subtle changes of the peripheral retinal vasculature without symptoms to severe disease with retinal neovascularization retinal exudates vitreoretinal adhesions peripheral vitreous opacities retinal folds and tractional retinal detachment The condition remarkably resembles retinopathy of prematurity but affected patients do not have a history of prematurity or supplementary oxygen use
The disorder is usually inherited as an autosomal dominant trait but few families show x-linked or autosomal recessive inheritance A significant number of patients with autosomal dominant FEVR show linkage to 11q13-q23 EVR1 Two genes in this locus have recently been shown to be associated with the disease FZD4 the gene that encodes for Frizzled-4 the Wnt receptor is one of them It has been estimated by recent studies that 20-30 of patients with autosomal dominant FEVR show mutations in FZD4 LRP5 low-density-lipoprotein receptor-related protein 5 a Wnt co-receptor was recently shown to be mutated in approximately 15 of cases One large autosomal dominant pedigree has shown linkage to 11p13-p12 locus EVR3 and this gene has not yet been identified It now becomes obvious that more genes are associated with the autosomal dominant type of the disease Most of the patients with the x-linked type have mutations in the Norrie disease gene EVR2 The autosomal recessive form of the disease is much rarer and linkage studies have not yet been performed
Aims The objectives of this protocol are to study the clinical characteristics of FEVR and also to assist in identifying the location and sequence of corresponding genes Since one of the genes so far identified LRP5 is also causing the osteoporosis-pseudoglioma syndrome an inherited disorder with severe osteoporosis we would also like to know if FEVR patients especially those with mutations in LRP5 also have some degree of osteoporosis Localization and identification of the responsible gene will help us understand the pathogenesis of FEVR and possibly the mechanism of retinal angiogenesis and lead to potential treatments
Methods Patients as well as available family members are to be evaluated by physical examination and fluorescein angiography in order to clinically characterize the inheritance pattern in each family Blood will be obtained by all participating subjects for the molecular studies
The disorder is usually inherited as an autosomal dominant trait but few families show x-linked or autosomal recessive inheritance A significant number of patients with autosomal dominant FEVR show linkage to 11q13-q23 EVR1 Two genes in this locus have recently been shown to be associated with the disease FZD4 the gene that encodes for Frizzled-4 the Wnt receptor is one of them It has been estimated by recent studies that 20-30 of patients with autosomal dominant FEVR show mutations in FZD4 LRP5 low-density-lipoprotein receptor-related protein 5 a Wnt co-receptor was recently shown to be mutated in approximately 15 of cases One large autosomal dominant pedigree has shown linkage to 11p13-p12 locus EVR3 and this gene has not yet been identified It now becomes obvious that more genes are associated with the autosomal dominant type of the disease Most of the patients with the x-linked type have mutations in the Norrie disease gene EVR2 The autosomal recessive form of the disease is much rarer and linkage studies have not yet been performed
Aims The objectives of this protocol are to study the clinical characteristics of FEVR and also to assist in identifying the location and sequence of corresponding genes Since one of the genes so far identified LRP5 is also causing the osteoporosis-pseudoglioma syndrome an inherited disorder with severe osteoporosis we would also like to know if FEVR patients especially those with mutations in LRP5 also have some degree of osteoporosis Localization and identification of the responsible gene will help us understand the pathogenesis of FEVR and possibly the mechanism of retinal angiogenesis and lead to potential treatments
Methods Patients as well as available family members are to be evaluated by physical examination and fluorescein angiography in order to clinically characterize the inheritance pattern in each family Blood will be obtained by all participating subjects for the molecular studies
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 05-EI-0104 | None | None | None |