Subretinal fibrosis in stargardt's disease: case report

Grandinetti, Alexandre Achille; Portella, Ezequiel; Arana, Jayme; Iskorostenski, Natasha

doi:10.1590/s0004-27492011000600015

Cited by 6 publications

(8 citation statements)

References 7 publications

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“…The presence of fibrotic scarring in the paramacular area [17], the dark choroid, the autofluorescence phenotype and the ERG results are consistent with an ABCA4 related retinopathy. The centrifugal expansion of fundus autofluorescence patterns in Stargardt disease has been described previously by Cukras et al [12,18].…”

Section: Resultsmentioning

confidence: 62%

Whole exome sequencing detects homozygosity for ABCA4 p.Arg602Trp missense mutation in a pediatric patient with rapidly progressive retinal dystrophy

et al. 2014

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BackgroundA pediatric patient presented with rapidly progressive vision loss, nyctalopia and retinal dystrophy. This is the first report of homozygosity for the p.Arg602Trp mutation in the ABCA4 gene. The child became legally blind within a period of 2 years.Case presentationAn eight year-old Hispanic female presented with bilateral decreased vision following a febrile gastrointestinal illness with nausea and vomiting. Extensive workup involved pediatric infectious disease and rheumatology consultations.Initial visual acuity was 20/60 at distance and 20/30 at near in both eyes. Rapidly progressive vision loss occurred during a 2-year period resulting in visual acuities of 20/200 at distance in both eyes. Fundus exam disclosed attenuated vessels and multiple subretinal blister-like elevations. Optical coherence tomography showed far more lesions than were clinically evident with different levels of elevation. Autofluorescence imagery showed dramatic and widespread geographic areas of atrophy. The deposits that appeared drusen-like on clinical exam were hyperfluorescent, consistent with lipofuscin deposits containing A2e (N-retinylidene-N-retinylethanolamine) indicative of RPE cell dysfunction. Electroretinography was consistent with cone dystrophy, with relative preservation of rod function. Blood analysis and rheumatology evaluation found no evidence of a diffuse post-infectious/inflammatory process. The unique and rapid progression of her subretinal blister-like lesions was documented by fluorescein angiography, optical coherence tomography, autofluorescence imagery, and fundus photography. Family pedigree history disclosed consanguinity, her parents being first cousins. DNA analysis by whole exomic sequencing revealed homozygosity of p.Arg602Trp in the ABCA4 gene.ConclusionThe pediatric patient presented with a striking clinical appearance and dramatic rate of progression that was clinically more characteristic of an infectious or inflammatory process. This case expands the diverse range of phenotypes attributed to ABCA4 mutations and further supports the role of whole exome sequencing as a powerful new tool available to aid clinicians in establishing diagnosis for challenging cases.

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Section: Resultsmentioning

confidence: 62%

Whole exome sequencing detects homozygosity for ABCA4 p.Arg602Trp missense mutation in a pediatric patient with rapidly progressive retinal dystrophy

et al. 2014

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“…Subretinal fibrosis can occur following minor ocular trauma in patients with STGD1. [60][61][62][63][64][65] Initially, an orange pigmented region (thought to be lipofuscin) is observed, which gives way to subretinal fibrosis and RPE hypertrophy. 64 Grandinetti et al 65 suggest that ocular trauma causes a release of excess lipofuscin which disrupts the RPE and leads to subretinal fibrosis and RPE hypertrophy.…”

Section: Specific Features Of Abca4rmentioning

confidence: 99%

“…[60][61][62][63][64][65] Initially, an orange pigmented region (thought to be lipofuscin) is observed, which gives way to subretinal fibrosis and RPE hypertrophy. 64 Grandinetti et al 65 suggest that ocular trauma causes a release of excess lipofuscin which disrupts the RPE and leads to subretinal fibrosis and RPE hypertrophy. Similarly, Gass et al 63 suggest that stored lipofuscin leads to engorgement and hypertrophy of the RPE and that trauma causes RPE disruption.…”

Section: Specific Features Of Abca4rmentioning

confidence: 99%

The role of multimodal imaging and vision function testing inABCA4-related retinopathies and their relevance to future therapeutic interventions

et al. 2021

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The aim of this review article is to describe the specific features of Stargardt disease and ABCA4 retinopathies (ABCA4R) using multimodal imaging and functional testing and to highlight their relevance to potential therapeutic interventions. Standardised measures of tissue loss, tissue function and rate of change over time using formal structured deep phenotyping in Stargardt disease and ABCA4R are key in diagnosis, and prognosis as well as when selecting cohorts for therapeutic intervention. In addition, a meticulous documentation of natural history will be invaluable in the future to compare treated with untreated retinas. Despite the familiarity with the term Stargardt disease, this eponymous classification alone is unhelpful when evaluating ABCA4R, as the ABCA4 gene is associated with a number of phenotypes, and a range of severity. Multimodal imaging, psychophysical and electrophysiologic measurements are necessary in diagnosing and characterising these differing retinopathies. A wide range of retinal dystrophy phenotypes are seen in association with ABCA4 mutations. In this article, these will be referred to as ABCA4R. These different phenotypes and the existence of phenocopies present a significant challenge to the clinician. Careful phenotypic characterisation coupled with the genotype enables the clinician to provide an accurate diagnosis, associated inheritance pattern and information regarding prognosis and management. This is particularly relevant now for recruiting to therapeutic trials, and in the future when therapies become available. The importance of accurate genotype-phenotype correlation studies cannot be overemphasised. This approach together with segregation studies can be vital in the identification of causal mutations when variants in more than one gene are being considered as possible. In this article, we give an overview of the current imaging, psychophysical and electrophysiological investigations, as well as current therapeutic research trials for retinopathies associated with the ABCA4 gene.

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“…In the literature, there are few articles that report on cases with STGD associated with subretinal fibrosis. In only 1 case, these lesions were not associated with a trauma, and none of the cases reported genetic analysis for the ABCA4 gene [9, 10, 11, 12, 13, 14, 15]. …”

Section: Introductionmentioning

confidence: 99%

Subretinal Fibrosis in Stargardts Disease with Fundus Flavimaculatus and ABCA4 Gene Mutation

Rossi

Testa

Attanasio

et al. 2012

Case Rep Ophthalmol

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Purpose: To report on 4 patients affected by Stargardt’s disease (STGD) with fundus flavimaculatus (FFM) and ABCA4 gene mutation associated with subretinal fibrosis. Methods: Four patients with a diagnosis of STGD were clinically examined. All 4 cases underwent a full ophthalmologic evaluation, including best-corrected visual acuity measured by the Snellen visual chart, biomicroscopic examination, fundus examination, fundus photography, electroretinogram, microperimetry, optical coherence tomography and fundus autofluorescence. All patients were subsequently screened for ABCA4 gene mutations, identified by microarray genotyping and confirmed by conventional DNA sequencing of the relevant exons. Results: In all 4 patients, ophthalmologic exam showed areas of subretinal fibrosis in different retinal sectors. In only 1 case, these lesions were correlated to an ocular trauma as confirmed by biomicroscopic examination of the anterior segment that showed a nuclear cataract dislocated to the superior site and vitreous opacities along the lens capsule. The other patients reported a lifestyle characterized by competitive sport activities. The performed instrumental diagnostic investigations confirmed the diagnosis of STGD with FFM in all patients. Moreover, in all 4 affected individuals, mutations in the ABCA4 gene were found. Conclusions: Patients with the diagnosis of STGD associated with FFM can show atypical fundus findings. We report on 4 patients affected by STGD with ABCA4 gene mutation associated with subretinal fibrosis. Our findings suggest that this phenomenon can be accelerated by ocular trauma and also by ocular microtrauma caused by sport activities, highlighting that lifestyle can play a role in the onset of these lesions.

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Subretinal fibrosis in stargardt's disease: case report

Cited by 6 publications

References 7 publications

Whole exome sequencing detects homozygosity for ABCA4 p.Arg602Trp missense mutation in a pediatric patient with rapidly progressive retinal dystrophy

Whole exome sequencing detects homozygosity for ABCA4 p.Arg602Trp missense mutation in a pediatric patient with rapidly progressive retinal dystrophy

The role of multimodal imaging and vision function testing inABCA4-related retinopathies and their relevance to future therapeutic interventions

Subretinal Fibrosis in Stargardts Disease with Fundus Flavimaculatus and ABCA4 Gene Mutation

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Subretinal fibrosis in stargardt's disease: case report

Cited by 6 publications

References 7 publications

Whole exome sequencing detects homozygosity for ABCA4 p.Arg602Trp missense mutation in a pediatric patient with rapidly progressive retinal dystrophy

Whole exome sequencing detects homozygosity for ABCA4 p.Arg602Trp missense mutation in a pediatric patient with rapidly progressive retinal dystrophy

The role of multimodal imaging and vision function testing inABCA4-related retinopathies and their relevance to future therapeutic interventions

Subretinal Fibrosis in Stargardts Disease with Fundus Flavimaculatus and ABCA4 Gene Mutation

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Subretinal Fibrosis in Stargardts Disease with Fundus Flavimaculatus and ABCA4 Gene Mutation