A Degeneração Retiniana de Início na Vida Adulta é uma doença hereditária da retina (ou seja, passada de pais para filhos) caracterizada por dificuldade de adaptação ao escuro e cegueira noturna, e pela formação de drusas (pequenos depósitos) na retina que surgem na idade adulta. Em seguida, ocorre uma degeneração das células responsáveis pela visão (os cones e bastonetes) que se manifesta por volta dos 50-60 anos de idade, resultando na perda da visão central. Alterações na parte da frente do olho também são observadas, como áreas mais finas na íris (a parte colorida do olho) ao redor da pupila, que deixam a luz passar (defeito de transiluminação), e as zônulas (fibras que seguram a lente natural do olho, o cristalino) que se inserem de forma anormalmente longa na parte da frente. Em estágios avançados da doença, podem ocorrer a formação de novos vasos sanguíneos anormais sob a retina (chamada neovascularização da coroide) e glaucoma.
Introdução
O que você precisa saber de cara
A Degeneração Retiniana de Início na Vida Adulta é uma doença hereditária da retina (ou seja, passada de pais para filhos) caracterizada por dificuldade de adaptação ao escuro e cegueira noturna, e pela formação de drusas (pequenos depósitos) na retina que surgem na idade adulta. Em seguida, ocorre uma degeneração das células responsáveis pela visão (os cones e bastonetes) que se manifesta por volta dos 50-60 anos de idade, resultando na perda da visão central. Alterações na parte da frente do olho também são observadas, como áreas mais finas na íris (a parte colorida do olho) ao redor da pupila, que deixam a luz passar (defeito de transiluminação), e as zônulas (fibras que seguram a lente natural do olho, o cristalino) que se inserem de forma anormalmente longa na parte da frente. Em estágios avançados da doença, podem ocorrer a formação de novos vasos sanguíneos anormais sob a retina (chamada neovascularização da coroide) e glaucoma.
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 12 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 30 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
1 gene identificado com associação a esta condição. Padrão de herança: Autosomal dominant.
Secreted
Late-onset retinal degeneration
Autosomal dominant disorder characterized by onset in the fifth to sixth decade with night blindness and punctate yellow-white deposits in the retinal fundus, progressing to severe central and peripheral degeneration, with choroidal neovascularization and chorioretinal atrophy.
Variantes genéticas (ClinVar)
116 variantes patogênicas registradas no ClinVar.
Classificação de variantes (ClinVar)
Distribuição de 95 variantes classificadas pelo ClinVar.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Degenerescência retiniana de início tardio
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Ensaios clínicos abertos e novidades científicas recentes
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Outros ensaios clínicos
Publicações mais relevantes
Drusenoid macular dystrophies in Singaporean Chinese: first report of Doyne honeycomb retinal dystrophy and late-onset retinal degeneration from Southeast Asia.
We report two ethnic Chinese families affected by distinct drusenoid inherited maculopathies: Doyne Honeycomb Retinal Dystrophy (DHRD) and Late-Onset Retinal Degeneration (L-ORD)-to expand their recognized phenotypic and ethnic spectrum. Affected members underwent multimodal ophthalmic imaging, including fundus photography, autofluorescence, optical coherence tomography, and widefield imaging. Genetic testing involved whole exome and targeted sequencing with haplotype and ancestry analysis. In the DHRD family, two members demonstrated peripapillary drusen, while one also had subretinal drusenoid deposits with minimal progression and no evidence of choroidal neovascularization (CNV). In the L-ORD family, two individuals showed progressive ellipsoid zone loss, outer retinal atrophy, and CNV with spontaneous regression. Pathogenic variants EFEMP1 c.1033C > T (p.Arg345Trp) and C1QTNF5 c.489C > G (p.Ser163Arg) were identified in the DHRD and L-ORD families, respectively. Genetic ancestry revealed no evidence of European admixture. DHRD and L-ORD, although originally believed to originate from European founder variants, are now established as probable mutational hotspots. We have now uncovered the first known family with DHRD in Southeast Asia, and the first L-ORD family without European heritage. Early recognition of inherited retinal diseases should be considered in patients with atypical drusen and family history of vision loss.
iPSC-derived retinal pigment epithelium: an in vitro platform to reproduce key cellular phenotypes and pathophysiology of retinal degenerative diseases.
Retinal pigment epithelium (RPE) atrophy is a significant cause of human blindness worldwide, occurring in polygenic diseases such as age-related macular degeneration (AMD) and monogenic diseases such as Stargardt diseases (STGD1) and late-onset retinal degeneration (L-ORD). The patient-induced pluripotent stem cells (iPSCs)-derived RPE (iRPE) model exhibits many advantages in understanding the cellular basis of pathological mechanisms of RPE atrophy. The iRPE model is based on iPSC-derived functionally mature and polarized RPE cells that reproduce several features of native RPE cells, such as phagocytosis of photoreceptor outer segments (POS) and replenishment of visual pigment. When derived from patients, iRPE are able to recapitulate critical cellular phenotypes of retinal degenerative diseases, such as the drusen-like sub-RPE deposits in the L-ORD and AMD models; lipid droplets and cholesterol accumulation in the STGD1 and AMD models. The iRPE model has helped discover the unexpected role of RPE in understanding retinal degenerative diseases, such as a cell-autonomous function of ABCA4 in STGD1. The iRPE model has helped uncover the pathological mechanism of retinal degenerative diseases, including the roles of alternate complement cascades and oxidative stress in AMD pathophysiology, abnormal POS processing in STGD1 and L-ORD, and its association with lipid accumulation. These studies have helped better understand-the role of RPE in retinal degenerative diseases, and molecular mechanisms underlying RPE atrophy, and have provided a basis to discover therapeutics to target RPE-associated diseases.
Biallelic loss-of-function variants in C19orf44 lead to retinal degeneration.
Inherited retinal diseases (IRDs) are a group of disorders often resulting in progressive vision loss, ultimately leading to blindness. A significant portion of their genetic causes remain unresolved, partly due to undiscovered disease-associated genes or variants. This study aimed to identify novel genetic links to IRDs. All patients underwent comprehensive ophthalmological evaluation, including retinal imaging (fundus autofluorescence and macular optical coherence tomography) and electroretinogram testing. Whole exome sequencing and whole genome sequencing were performed on patients with clinically unsolved IRD, and data were analysed using an in-house pipeline to identify causal variants. Subsequently, Sanger sequencing was performed to confirm identified variants. Three unrelated patients from Europe, Middle East and East Asia were identified with unique late-onset retinal degeneration (Stargardt-like phenotype) associated with biallelic loss-of-function (LoF) variants in C19orf44 (HGNC: 26141), a gene of unknown function. The homozygous variant NM_032207.2:c.549_550del;p.Ser185Profs*2 was identified in two unrelated patients (European and Middle Eastern). Moreover, an East Asian patient had likely compound heterozygous LoF variants (NM_032207.2:c.1168C>T;p.Gln390*/c.976_977del;p.Leu326Lysfs*15). Our findings establish C19orf44 as a novel disease-causing gene for IRD with Stargardt-like phenotype, expanding the genetic landscape of retinal degeneration.
Late-Onset Retinal Degeneration.
Patients with late-onset retinal degeneration (LORD) usually present with nyctalopia in the fifth or sixth decade of life. The fundus shows yellowish-white, punctate deposits, usually progressive and giving rise to scalloped areas of retinal pigment epithelium (RPE) atrophy in the mid-periphery and posterior pole (Fig. 23.1). The anterior segment shows elongated zonules with central lens insertion and transillumination defect in the iris, due to iris atrophy.
C1QTNF5 missense variant causing autosomal dominant gyrate atrophy-like choroidal dystrophy.
It was recently proposed that the c.538C>G; p.(Q180E) missense variant in the C1QTNF5 gene leads to autosomal dominant gyrate atrophy-like choroidal dystrophy (adGALCD). AdGALCD has a phenotypic overlap with other chorioretinal dystrophies but exhibits not the typical characteristics of late-onset retinal degeneration (L-ORD). Here, we report a 70-year-old female simplex patient with adGALCD. Comprehensive ophthalmic examinations included visual field testing and multimodal retinal imaging with optical coherence tomography (OCT), short-wavelength-, and near-infrared fundus autofluorescence. Genetic testing was performed using whole exome sequencing. The patient presented with bilateral progressive concentric visual field defects and photophobia for about 8 years. Best corrected visual acuity was 20/40 in the right and 20/32 in the left eye, respectively. On fundus examination, symmetric areas of large peripheral and peripapillary chorioretinal atrophy with foveal sparing were observed with corresponding visual field defects. Fundus autofluorescence imaging showed a central island of preserved autofluorescence surrounded by an extinguished signal in the atrophic areas. OCT imaging showed preserved central retinal pigment epithelium and ellipsoid zone with peripapillary and peripheral atrophy of both layers. Genetic testing revealed a heterozygous missense variant p.(Q180E) in the C1QTNF5 gene. We confirm that the c.538C>G; p.(Q180E) missense variant in the C1QTNF5 gene may lead to adGALCD.
Publicações recentes
Drusenoid macular dystrophies in Singaporean Chinese: first report of Doyne honeycomb retinal dystrophy and late-onset retinal degeneration from Southeast Asia.
Biallelic loss-of-function variants in C19orf44 lead to retinal degeneration.
Late-Onset Retinal Degeneration.
C1QTNF5 missense variant causing autosomal dominant gyrate atrophy-like choroidal dystrophy.
Late-Onset Retinal Degeneration: Clinical Features and C1QTNF5/CTRP5 Function.
📚 EuropePMC45 artigos no totalmostrando 61
Drusenoid macular dystrophies in Singaporean Chinese: first report of Doyne honeycomb retinal dystrophy and late-onset retinal degeneration from Southeast Asia.
Ophthalmic geneticsBiallelic loss-of-function variants in C19orf44 lead to retinal degeneration.
Journal of medical geneticsLate-Onset Retinal Degeneration.
Advances in experimental medicine and biologyC1QTNF5 missense variant causing autosomal dominant gyrate atrophy-like choroidal dystrophy.
Ophthalmic geneticsLate-Onset Retinal Degeneration: Clinical Features and C1QTNF5/CTRP5 Function.
Advances in experimental medicine and biologyiPSC-derived retinal pigment epithelium: an in vitro platform to reproduce key cellular phenotypes and pathophysiology of retinal degenerative diseases.
Stem cells translational medicineTreatment Strategy With Gene Editing for Late-Onset Retinal Degeneration Caused by a Founder Variant in C1QTNF5.
Investigative ophthalmology & visual scienceAn incipient late-onset retinal degeneration with a C1QTNF5 mutation: a case report with an 11-year follow-up.
Documenta ophthalmologica. Advances in ophthalmologyLongitudinal Changes of Retinal Structure in Molecularly Confirmed C1QTNF5 Patients With Late-Onset Retinal Degeneration.
Translational vision science & technologyApplication of Electrophysiology in Non-Macular Inherited Retinal Dystrophies.
Journal of clinical medicineOuter retinal corrugations in late-onset retinal degeneration: a diagnostic finding demonstrated with multimodal imaging.
BMJ open ophthalmologyLipidUNet-Machine Learning-Based Method of Characterization and Quantification of Lipid Deposits Using iPSC-Derived Retinal Pigment Epithelium.
Journal of visualized experiments : JoVEMacular neovascularization in inherited retinal diseases: A review.
Survey of ophthalmologyA Novel Mouse Model for Late-Onset Retinal Degeneration (L-ORD) Develops RPE Abnormalities Due to the Loss of C1qtnf5/Ctrp5.
Advances in experimental medicine and biologyMICROPERIMETRY IN FOVEAL-SPARING ATROPHIC LATE-ONSET RETINAL DEGENERATION.
Retina (Philadelphia, Pa.)MACULAR NEOVASCULARIZATION IN A CASE OF LATE-ONSET RETINAL DEGENERATION TREATED WITH AFLIBERCEPT.
Retinal cases & brief reportsEstablishment and characterization of an iPSC line (UCLi023-A) derived from a Late-Onset Retinal Degeneration patient carrying a founder mutation in C1QTNF5.
Stem cell researchAnterior segment phenotypic changes in late-onset retinal degeneration with Ser163Arg mutation in CTRP5/C1QTNF5.
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle OphthalmologieExtensive temporal subretinal drusenoid deposits as an early manifestation of late-onset retinal degeneration.
Canadian journal of ophthalmology. Journal canadien d'ophtalmologieHomozygous Knockout of Cep250 Leads to a Relatively Late-Onset Retinal Degeneration and Sensorineural Hearing Loss in Mice.
Translational vision science & technologyApplication of multicolour reflectance imaging for the characterisation of inherited retinal disorders.
European journal of ophthalmologyDistinct Phenotypic Consequences of Pathogenic Mutants Associated with Late-Onset Retinal Degeneration.
The American journal of pathologyLate-Onset Retinal Degeneration: Clinical Perspectives.
Clinical ophthalmology (Auckland, N.Z.)Specific ablation of Hippo signalling component Yap1 in retinal progenitors and Müller cells results in late onset retinal degeneration.
Journal of cellular physiologySingle-cell-resolution map of human retinal pigment epithelium helps discover subpopulations with differential disease sensitivity.
Proceedings of the National Academy of Sciences of the United States of AmericaAMPK modulation ameliorates dominant disease phenotypes of CTRP5 variant in retinal degeneration.
Communications biologyMASSIVE ADVANCING NONEXUDATIVE TYPE 1 CHOROIDAL NEOVASCULARIZATION IN CTRP5 LATE-ONSET RETINAL DEGENERATION: Longitudinal Findings on Multimodal Imaging and Implications for Age-Related Macular Degeneration.
Retina (Philadelphia, Pa.)Longitudinal phenotypic study of late-onset retinal degeneration due to a founder variant c.562C>A p.(Pro188Thr) in the C1QTNF5 gene.
Ophthalmic geneticsAutosomal Dominant Gyrate Atrophy-Like Choroidal Dystrophy Revisited: 45 Years Follow-Up and Association with a Novel C1QTNF5 Missense Variant.
International journal of molecular sciencesReticular Pseudodrusen in Late-Onset Retinal Degeneration.
Ophthalmology. RetinaQUANTITATIVE ANALYSIS OF LONGITUDINAL CHANGES IN MULTIMODAL IMAGING OF LATE-ONSET RETINAL DEGENERATION.
Retina (Philadelphia, Pa.)CHARACTERIZING THE NATURAL HISTORY OF FOVEAL-SPARING ATROPHIC LATE-ONSET RETINAL DEGENERATION.
Retina (Philadelphia, Pa.)THE PROGRESSION OF MACULAR STRUCTURAL AND FUNCTIONAL CHANGES IN LATE-ONSET RETINAL DEGENERATION.
Retinal cases & brief reportsQuantifying the Separation Between the Retinal Pigment Epithelium and Bruch's Membrane using Optical Coherence Tomography in Patients with Inherited Macular Degeneration.
Translational vision science & technologyStudies of the Periciliary Membrane Complex in the Syrian Hamster Photoreceptor.
Advances in experimental medicine and biologyMissense variants in the conserved transmembrane M2 protein domain of KCNJ13 associated with retinovascular changes in humans and zebrafish.
Experimental eye researchLate-onset retinal degeneration pathology due to mutations in CTRP5 is mediated through HTRA1.
Aging cellLate-onset night blindness with peripheral flecks accompanied by progressive trickle-like macular degeneration.
Documenta ophthalmologica. Advances in ophthalmologyChoroidal Neovascularization in Late-Onset Retinal Macular Degeneration.
Ophthalmology. RetinaLongitudinal adaptive optics fluorescence microscopy reveals cellular mosaicism in patients.
JCI insightPhagosomal and mitochondrial alterations in RPE may contribute to KCNJ13 retinopathy.
Scientific reportsMultimodal imaging of late-onset retinal degeneration complicated by bilateral choroidal neovascularization.
Eye (London, England)Mouse Idh3a mutations cause retinal degeneration and reduced mitochondrial function.
Disease models & mechanismsCone Photoreceptor Cell Segmentation and Diameter Measurement on Adaptive Optics Images Using Circularly Constrained Active Contour Model.
Investigative ophthalmology & visual scienceWhole-exome sequencing revealed HKDC1 as a candidate gene associated with autosomal-recessive retinitis pigmentosa.
Human molecular geneticsUsherin defects lead to early-onset retinal dysfunction in zebrafish.
Experimental eye researchCo-Expression of Wild-Type and Mutant S163R C1QTNF5 in Retinal Pigment Epithelium.
Advances in experimental medicine and biologyNovel pathogenic mutations in C1QTNF5 support a dominant negative disease mechanism in late-onset retinal degeneration.
Scientific reportsCataract surgery in patients with late-onset retinal degeneration.
Journal of cataract and refractive surgeryAbsence of Sigma 1 Receptor Accelerates Photoreceptor Cell Death in a Murine Model of Retinitis Pigmentosa.
Investigative ophthalmology & visual scienceBiallelic Mutation of ARHGEF18, Involved in the Determination of Epithelial Apicobasal Polarity, Causes Adult-Onset Retinal Degeneration.
American journal of human geneticsLONGITUDINAL STRUCTURAL CHANGES IN LATE-ONSET RETINAL DEGENERATION.
Retina (Philadelphia, Pa.)Distinct Genetic Risk Profile of the Rapidly Progressing Diffuse-Trickling Subtype of Geographic Atrophy in Age-Related Macular Degeneration (AMD).
Investigative ophthalmology & visual scienceLoss of CTRP5 improves insulin action and hepatic steatosis.
American journal of physiology. Endocrinology and metabolismCanine genome assembly correction facilitates identification of a MAP9 deletion as a potential age of onset modifier for RPGRIP1-associated canine retinal degeneration.
Mammalian genome : official journal of the International Mammalian Genome SocietyPathological Effects of Mutant C1QTNF5 (S163R) Expression in Murine Retinal Pigment Epithelium.
Investigative ophthalmology & visual scienceA novel homozygous truncating GNAT1 mutation implicated in retinal degeneration.
The British journal of ophthalmologyApplication of Whole Exome Sequencing in Six Families with an Initial Diagnosis of Autosomal Dominant Retinitis Pigmentosa: Lessons Learned.
PloS oneImprovement of retinal function in L-ORD after prolonged dark adaptation.
Canadian journal of ophthalmology. Journal canadien d'ophtalmologie[Management of a choroidal neovascular membrane with aflibercept in a patient with a rare, autosomal dominant late-onset retinal degeneration: case report].
Journal francais d'ophtalmologiePresence of rd8 mutation does not alter the ocular phenotype of late-onset retinal degeneration mouse model.
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Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Drusenoid macular dystrophies in Singaporean Chinese: first report of Doyne honeycomb retinal dystrophy and late-onset retinal degeneration from Southeast Asia.
- iPSC-derived retinal pigment epithelium: an in vitro platform to reproduce key cellular phenotypes and pathophysiology of retinal degenerative diseases.
- Biallelic loss-of-function variants in C19orf44 lead to retinal degeneration.
- Late-Onset Retinal Degeneration.
- C1QTNF5 missense variant causing autosomal dominant gyrate atrophy-like choroidal dystrophy.
- Late-Onset Retinal Degeneration: Clinical Features and C1QTNF5/CTRP5 Function.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:67042(Orphanet)
- OMIM OMIM:605670(OMIM)
- MONDO:0011579(MONDO)
- GARD:4357(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Q32136602(Wikidata)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
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