ENFERMEDAD DE STARGARDT PDF
Stargardt disease is the most common form of inherited juvenile macular degeneration. The progressive vision loss associated with Stargardt disease is caused. Stargardt disease is the most common form of inherited juvenile macular degeneration. ¿Qué es la enfermedad de Stargardt? Written By. Definition. Stargardt disease (STGD) is the most common childhood recessively inherited macular dystrophy. The condition has a genetic basis.
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CC HPO: A locus for Stargardt disease mapped to chromosome 13q34 and designated STGD2 was found to be in error; the disorder in the family in which the linkage was made was correctly mapped to chromosome 6q14 STGD3. One patient with a diagnosis of juvenile macular degeneration was found to be compound heterozygous for mutations in the CNGB3 gene on chromosome 8q.
FFM has enfer,edad later age of onset. If loss of visual acuity begins in the first 2 decades, the designation Stargardt disease is preferred; if it begins later in life and has a more progressive course, the term FFM is preferred Weleber, Stargardt disease is one of the most frequent causes of macular degeneration in childhood.
It has onset between 7 and 12 years, a rapidly progressive course, and a poor final visual outcome.
Although visual acuity is severely reduced, peripheral visual fields remain normal throughout life. Degeneration limited to the macular area of the retina was described in multiple sibs by Ford and by Walsh Fundus flavimaculatus, which is a form of fleck fundus disease seederives its name from the occurrence of many yellow spots rather uniformly distributed over the fundus.
In some older patients the flecks fade with stargarddt as atrophy of the retinal pigment epithelium RPE increases.
Round, linear, or pisciform lesions are distributed in the posterior pole, sometimes with extension to the equator, and with macular involvement. Network atrophy of the retinal pigment epithelium, and choroidal vascular atrophy are features. Central visual loss, loss of color vision, statgardt, paracentral scotoma, and slow dark adaptation are features. This is probably an autosomal recessive disorder. Klien and Krill observed a ‘familial incidence No parental consanguinity was described.
In 1 efnermedad the father and 2 daughters were affected. In the instance of an affected brother and sister, the father was black and the mother white. Krill and Deutman concluded that recessive macular dystrophy was the disorder described and beautifully illustrated stargarxt Stargardtand efermedad was the disorder that Franceschetti renamed fundus flavimaculatus. Krill and Deutman suggested the possibility statgardt a rarer, phenotypically indistinguishable, autosomal dominant form.
Hadden and Gass presented evidence that fundus flavimaculatus is the same as the Stargardt form of macular dystrophy. Pearce reported 4 families with 9 affected persons. In 1 instance, 2 affected persons married and both of their children were affected. Carpel and Kalina described 3 affected sisters. Isashiki and Ohba remarked on variable expression. Among the 3 children of normal first-cousin parents were a year-old boy with bull’s eye macular change and sparse fundus flavimaculatus type flecks, and an year-old girl with numerous fleck lesions of FFM throughout the posterior fundus and virtually no macular change.
As pointed out by WeleberRosehr found that 2 of the original patients described by Stargardtwhen seen almost 50 years later, still did not complain of night blindness and their visual fields were, at most, only mildly constricted. The macular regions showed marked atrophy in each patient, and 1 patient had peripheral pigment clumping and drusen. Whereas Stargardt disease shows juvenile to young adult age of onset, the clinically similar retinal disorder fundus flavimaculatus ennfermedad displays later age of onset and slower progression.
Stargardt Disease | National Eye Institute
Histologically the disorder is characterized by subretinal deposition of lipofuscin-like material. As pointed out by MeitingerStargardt disease had always been considered to be a retinal degeneration originating in the retinal pigment epithelium, which underlies the photoreceptors, predominantly cones, of the macula.
Thus, the findings of Allikmets et al. To understand better the shared characteristics of Stargardt macular dystrophy and fundus flavimaculatus, Armstrong et al. They found that morphologic changes and retinal function degeneration were more severe in patients with FFM than in patients with STGD. At least 1 disease -causing mutation in the ABCA4 gene was found in 11 of the patients. Central scotomas were present in all patients, although the fovea was spared in df.
The earliest cone spacing abnormalities were observed in regions of homogeneous AF, normal visual function, and normal outer retinal structure. Outer retinal structure and AF were most normal near the optic disc. Longitudinal studies showed progressive increases in AF followed by reduced AF associated with losses of visual sensitivity, outer retinal layers, and cones.
Cone loss predominated closer to the fovea with a greater contribution from rod loss in the periphery. Median ages of onset and baseline examination were 8. Median baseline logarithm of the minimum angle of resolution visual acuity was 0. SD-OCT detected foveal outer retinal disruption in all 21 patients with available images. Among the patients were 37 with 2 or more ABCA4 mutations, 7 with 1 ABCA4 mutation and the presence of yellow-white flecks, and 7 not known to have an ABCA4 mutation but with yellow-white flecks and either a dark choroid or an atrophic macular lesion.
The mean age at onset was 7. On fluorescein angiography FAa dark choroid was found in 21 of 29 patients. On fundus autofluorescence FAFthere was centrifugal expansion of disseminated atrophic spots, which progressed to eventual profound chorioretinal atrophy.
No correlation between ffERG abnormalities and rate of visual loss was found. Thirteen of 25 patients had progressive ffERG abnormalities. Similarly, mean sensitivity within 2 degrees of the foveal region was significantly better in eyes with hyper-FAF than in eyes with hypo-FAF.
Commenting on the work of Radu et al. He suggested that it is not a coincidence that the macula of the retina also has the highest concentration of cis-retinal-containing visual pigment, a feature reflecting, in part, the packing density of cone and rod photoreceptor cells.
The heightened capacity for photon absorption conferred by the density of visual pigment in the macula translates into a higher probability that all-trans-retinal will be available for A2E formation. Sparrow noted that the well-known cause of birth defects by orally administered isotretinoin would be problematic for female patients with STGD who might be treated with this agent.
None stargardf the 80 controls had these missense mutations. Three other patients had other missense polymorphisms. The RPE participates in the continual renewal of visual pigments and of photoreceptor outer segments.
The best-studied molecules that cycle between photoreceptors and the RPE are the retinoids. Histopathologic studies of the eyes in Stargardt diseaseand its somewhat enffermedad variant fundus flavimaculatus FFMshow massive accumulation of lysosomal material similar to lipofuscin within RPE cells.
Orphanet: Enfermedad de Stargardt
Slowing of retinoid cycle kinetics was not present in all patients; when present, it was not homogeneous across the retina; and the extent of slowing correlated well with the degree of degeneration.
The orderly relationship between these phenotypic features permitted the development of a model of disease sequence in retinal degeneration due to ABCA4 mutation, which stargxrdt lipofuscin accumulation as a key early component of disease expression with abnormal slowing of the rod and cone retinoid cycle occurring at later stages of the disease sequence.
Stargardt disease is the most common hereditary recessive macular dystrophy, with an estimated incidence of 1 in 10, Blacharski, By genetic linkage analysis, using CA n microsatellite markers of known chromosomal location Weissenbach et al. The enfermerad maximum lod score was 6.
From linkage studies, Gerber et al. They considered 1p13 to be the likely location of the gene that is mutant stargarvt these allelic disorders.
The age at onset ranged starggardt 17 to 60 years in adult patients. The maximum 2-point lod score for all families combined was 5. In 1 family they encountered an affected female who, on the basis of haplotype analysis, carried only 1 disease allele.
Stargardt disease/Fundus flavimaculatus
They reported apparent nonpenetrance in a year-old male. Some families exhibited concordance of ABCA4 alleles with the macular degeneration phenotype, but others did not. Exudative ARMD was uncommon among both probands and sibs. The patient’s father was heterozygous for the mutation.
In a patient with juvenile macular degeneration in whom mutation in the ABCA4 gene was excluded Briggs et al. Stargardt disease had not previously been associated with mutations in the cone channel subunits.
Pal Singh et al. Affected individuals in both families had early-onset visual loss, diminished rod and cone electroretinographic responses, and widespread atrophy of the retinal pigment epithelium. They also found a higher proportion of definitely or possibly deleterious variants in these children compared with 64 adult-onset ABCA4-positive STGD patients.
They found that nonsense mutations truncating the ABCA4 protein consistently led to Stargardt diseasewhereas all mutations they identified in the ABCA4 gene in fundus flavimaculatus were missense mutations affecting uncharged amino acids. In the patient with RP19, a partial deletion of the maternal ABCA4 gene was presumed to be the source of a null allele, although this was not conclusively proven. Whereas phenotypic differences were not obvious on the basis of either qualitative fundus autofluorescence AF or SD-OCT, with quantitative AF qAFthe 2 groups of patients were clearly distinguishable.
Stargardt disease has sometimes been called central retinitis pigmentosa or retinitis pigmentosa with macular involvement. However, ordinary retinitis pigmentosa does not affect the macula. Long-term follow-up of Stargardt ‘s disease and fundus flavimaculatus.
Genotype-phenotype analysis of ABCR variants in macular degeneration probands and siblings. Histopathology and immunocytochemistry of the neurosensory retina in fundus flavimaculatus. Retinal Dystrophies and Degenerations. A family study of fundus flavimaculatus. Cone photoreceptor abnormalities correlate with vision loss in patients with Stargardt disease.
Mutations in ABCA4 result in accumulation of lipofuscin before slowing of the retinoid cycle: Case of Stargardt disease caused by uniparental isodisomy. Charles C Thomas pub. Ueber tapeto-retinale Degenerationen in Kindesalter. Entwicklung und Fortschitt in der Augenkeilkunde. Clinical and molecular characteristics of childhood-onset Stargardt disease. A gene for late-onset fundus flavimaculatus with macular dystrophy maps to chromosome 1p Fundus flavimaculatus and Stargardt ‘s disease.
Genetic fine mapping of the gene for recessive Stargardt disease.