Novel clinical presentation of a CRX rod-cone dystrophy

2021 ◽  
Vol 14 (4) ◽  
pp. e233711
Author(s):  
Luis Alonso Gonzalez-Gonzalez ◽  
Hannah Scanga ◽  
Elias Traboulsi ◽  
Ken K Nischal
Keyword(s):  
Optic Nerve ◽  
Clinical Presentation ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Dystrophy ◽  
Young Male ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic ◽  
Cone Dystrophy ◽  
Single Family

We describe a novel clinical presentation of a CRX rod-cone dystrophy in a single family. Two boys ages 6 and 12 years presented with clinical and optical coherence tomography features suggestive of X-linked retinoschisis, but with optic nerve swelling without increased intracranial pressure. One patient had an electronegative electroretinogram (ERG) and the other had rod-cone dysfunction. Neither had retinoschisin (RS1) gene mutations. Biological mother and sister presented with retinal pigment epithelium (RPE) changes and abnormal cone-rod ERG responses. On further testing, next generation sequencing with array comparative genomic hybridisation showed a deletion in exon 4 of the CRX gene. Cystoid maculopathy in young male children can be difficult to distinguish from RS1-associated schisis. Phenotypic variants within a family must prompt a thorough retinal dystrophy evaluation even with electronegative ERG in the presenting child. This novel phenotype for CRX presents with optic nerve swelling and cystoid maculopathy in men, and RPE changes in women.

Retinal dystrophy associated with Danon disease and pathogenic mechanism through LAMP2-mutated retinal pigment epithelium

2019 ◽  
Vol 30 (3) ◽  
pp. 570-578 ◽  
Author(s):  
Masaya Fukushima ◽  
Tatsuya Inoue ◽  
Takashi Miyai ◽  
Ryo Obata
Keyword(s):  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Intracellular Localization ◽  
Retinal Dystrophy ◽  
Wild Type Mouse ◽  
Biological Study ◽  
Mouse Retina ◽  
Cone Dystrophy ◽  
Danon Disease

Introduction: Lysosome-associated membrane protein 2 plays an important role in autophagy and lysosomal function and its mutation is responsible for pathogenesis of Danon disease, which can cause retinopathy, though its pathophysiological contribution to retinal dysfunction remains unclear. The purpose of our research is to report the first case of Japanese Danon disease retinopathy and to understand how LAMP2 dysfunction contributes to pathogenesis of retinopathy. Methods: One case underwent ophthalmic examination including slit-lamp exam, fundus imaging, visual field testing, and electroretinogram. In molecular biological study, relative messenger RNA expression levels of three splicing variants of Lamp2 or LAMP2 in wild type mouse retina and retinal pigment epithelium, human retinal pigment epithelium cell line adult retinal pigment epithelium-19 were quantified. LAMP2 was knocked down by small interfering RNA in adult retinal pigment epithelium-19 and its effect to LC3, an autophagy marker, was assessed by Western blotting. Intracellular localization of LAMP2 and LC3 in untreated and LAMP2-knocked-down adult retinal pigment epithelium-19 was analyzed by confocal microscopy. Results: Our case manifested cone dystrophy in both eyes. In mice, expression of Lamp2a and Lamp2b was significantly higher in retinal pigment epithelium than that in neural retina. Expression of Lamp2a and Lamp2b were significantly higher than that of Lamp2c in mouse retinal pigment epithelium. Adult retinal pigment epithelium-19 cells showed similar LAMP2 expression pattern to mouse retinal pigment epithelium. LAMP2 knockdown in adult retinal pigment epithelium-19 reduced LC3-II amount and the number and size of autophagosome. Discussion: We report a Japanese case of Danon disease retinopathy, and our study implies that LAMP2 plays an important role in autophagosome formation in retinal pigment epithelium.

scholarly journals Giant Idiopathic Angioid Streaks

2020 ◽  
Author(s):  
Brijesh Takkar ◽  
Anubha Rathi ◽  
Pradeep Venkatesh ◽  
Atul Kumar
Keyword(s):  
Imaging Techniques ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Young Male ◽  
Significant Finding ◽  
Angioid Streaks ◽  
Retinal Hemorrhages ◽  
Swept Source ◽  
Steroid Abuse ◽  
Membrane Complex

Purpose: To present a case of gigantic idiopathic angioid streaks. Case Report: A young male presented with macular choroidal neovascular membrane (CNVM) and peripheral retinal hemorrhages secondary to angioid streaks. Swept source optical coherence tomography (SSOCT) and ultrawide field imaging were performed. The latter revealed extension of the angioid streaks up to the equator in both eyes. SSOCT showed breaks in the retinal pigment epithelium-Bruch’s membrane complex in the area of peripheral retinal hemorrhages. The patient was extensively worked up for systemic associations, and the only significant finding was a long history of steroid abuse in the past. Conclusion: Advanced imaging techniques helped to diagnose angioid streaks in this patient. The possible role of steroid abuse in accentuating the presentation of angioid streaks may be explored further.

Genomic characterisation of multiple myeloma: study of a Portuguese cohort

2021 ◽  
pp. jclinpath-2020-207204
Author(s):  
Alexandra Couto Oliveira ◽  
Ilda Patrícia Ribeiro ◽  
Luís Miguel Pires ◽  
Ana Cristina Gonçalves ◽  
Artur Paiva ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Prognostic Value ◽  
Clinical Presentation ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic ◽  
Genomic Alterations ◽  
Genomic Complexity ◽  
Genome Wide ◽  
Trisomy 9

Multiple myeloma (MM) genomic complexity reflects in the variable patients’ clinical presentation. Genome-wide studies seem to be a reasonable alternative to identify critical genomic lesions. In the current study, we have performed the genomic characterisation of a Portuguese cohort of patients with MM by array comparative genomic hybridisation. Overall, the most frequently detected alterations were 13q deletions, gains of 1q, 19p, 15q, 5p and 7p and trisomy 9. Even though some identified genomic alterations were previously associated with a prognostic value, other abnormalities remain with unknown, but putative significance for patients’ clinical practice. These genomic alterations should be further assessed as possible biomarkers.

Diffuse Pigmented Lesions in the Outer Retina: An Unusual Fundus Appearance

2019 ◽  
Vol 4 (3) ◽  
pp. 243-247
Author(s):  
Matthew D. Benson ◽  
Uriel Rubin ◽  
Marvi Cheema ◽  
Ian M. MacDonald ◽  
Matthew T.S. Tennant ◽  
...  
Keyword(s):  
Phenotypic Diversity ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Dystrophy ◽  
Full Field ◽  
Panel Testing ◽  
Pigmented Lesions ◽  
Hereditary Retinal Dystrophy ◽  
Ultrasound Findings ◽  
Chest X Ray

Purpose: This report describes and provides a differential diagnosis for a patient with unusual bilateral retinal pigmented lesions. Methods: A 40-year-old woman was found to have multiple flat, gray lesions scattered across her fundi, becoming larger and more confluent toward the periphery. There were small drusenlike deposits in her foveae. The hyperpigmented lesions demonstrated hypoautofluorescence with thickening of the retinal pigment epithelium and disruption of the overlying layers on optical coherence tomography (OCT). Full-field electroretinography revealed generalized reduced a- and b-wave amplitudes. Results: Chest x-ray, breast ultrasound, mammography, and pelvic ultrasound findings were negative for malignant etiologic factors. Panel testing results for hereditary retinal dystrophy were negative. Conclusions: Although the clinical and OCT appearance of the lesions is similar to congenital grouped pigmentation, the symmetric and bilateral nature of ocular findings coupled with electroretinographic changes suggest a possible retinal dystrophy. This case adds to the phenotypic diversity of pigmented fundus lesions.

Expanding the retinal phenotype of RP1: from retinitis pigmentosa to a novel and singular macular dystrophy

2019 ◽  
Vol 104 (2) ◽  
pp. 173-181 ◽  
Author(s):  
Marina Riera ◽  
Víctor Abad-Morales ◽  
Rafael Navarro ◽  
Sheila Ruiz-Nogales ◽  
Pilar Méndez-Vendrell ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Retinitis Pigmentosa ◽  
Pigment Epithelium ◽  
Fundus Autofluorescence ◽  
Retinal Pigment ◽  
Retinal Dystrophy ◽  
Macular Dystrophy ◽  
Nucleotide Polymorphisms ◽  
Autofluorescence Imaging ◽  
New Genotype

PurposeThis study aimed to identify the underlying genetic cause(s) of inherited retinal dystrophy (IRD) in 12 families of Kuwaiti origin affected by macular dystrophy and four Spanish patients affected by retinitis pigmentosa (RP).MethodsClinical diagnoses were based on standard ophthalmic evaluations (best-corrected visual acuity, retinography, fundus autofluorescence imaging, optical coherence tomography, electroretinography and visual field tests). Panel-based whole exome sequencing was used to simultaneously analyse 224 IRD genes in one affected member of each family. The putative causative variants were confirmed by Sanger sequencing and cosegregation analyses. Haplotype analysis was performed using single nucleotide polymorphisms.ResultsA homozygous missense mutation c.606C>A (p.Asp202Glu) in RP1 was found to be the molecular cause of IRD in all 12 families from Kuwait. These patients exhibited comparable symptoms, including progressive decline in visual acuity since adolescence. Fundus autofluorescence images revealed bilateral macular retinal pigment epithelium disturbances, with neither perimacular flecks nor peripheral alterations. A shared haplotype spanning at least 1.1 Mb was identified in all families, suggesting a founder effect. Furthermore, RP1 variants involving nonsense and/or frameshifting mutations (three of them novel) were identified in three Spanish autosomal-recessive RP families and one dominant RP pedigree.ConclusionThis study describes, for the first time, a macular dystrophy phenotype caused by an RP1 mutation; establishing a new genotype-phenotype correlation in this gene, expanding its mutation spectrum and further highlighting the clinical heterogeneity associated with IRD.

Unusual presentation of early-onset X-linked retinoschisis: Report after 1 year of multimodal follow-up

2020 ◽  
pp. 112067212091672
Author(s):  
Andrea Lembo ◽  
Giacomo Maria Bacci ◽  
Massimiliano Serafino ◽  
Stefano Lucentini ◽  
Roberto Caputo ◽  
...  
Keyword(s):  
Retinal Detachment ◽  
Early Onset ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Dystrophy ◽  
Unusual Presentation ◽  
Macular Dystrophy ◽  
Wide Field ◽  
The Right

Purpose: To describe the unusual presentation, diagnosis, and clinical course of an early-onset X-linked infantile retinoschisis Case report: A 6-month-old infant presented with strabismus and poor fixation. After the detection of bilateral intraretinal hemorrhage and diffuse dystrophic retinal pattern at indirect ophthalmoscopy, the patient received a complete evaluation under anesthesia. Retinal wide-field imaging, spectral domain optical coherence tomography, and electroretinogram were performed and revealed a retinoschisis involving the posterior pole and the inferior periphery in the right eye. In the left eye, an inferior retinal detachment extending to the macula was detected. Blood sample and genetic counseling were required in the strong suspicion of an inherited retinal dystrophy. Genetic tests confirmed the diagnosis of X-linked retinoschisis (RS1 gene mutation). After consultation with a pediatric vitreoretinal surgeon, a wait and see strategy was chosen. The follow up visits showed a surprisingly good natural course of the disease. Conclusion: X-linked retinoschisis is a well-known inherited retinal disease potentially affecting young children as early as 3 months old. In this case, the stunning presentation (diffuse retinal pigment epithelium dystrophic changes resembling a macular dystrophy) and the positive course of the disease (resolution of macular retinal detachment in the left eye and stability of schisis in the right eye) arise some interesting considerations about the necessity of an early surgical treatment.

CRB1-associated retinal dystrophies in a Belgian cohort: genetic characteristics and long-term clinical follow-up

2021 ◽  
pp. bjophthalmol-2020-316781
Author(s):  
Mays Talib ◽  
Caroline Van Cauwenbergh ◽  
Julie De Zaeytijd ◽  
David Van Wynsberghe ◽  
Elfride De Baere ◽  
...  
Keyword(s):  
Visual Function ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Posterior Uveitis ◽  
Cone Dystrophy ◽  
Macular Dystrophy ◽  
Genetic Characteristics ◽  
Retinal Dystrophies ◽  
Retinal Structure

AimTo investigate the natural history in a Belgian cohort of CRB1-associated retinal dystrophies.MethodsAn in-depth retrospective study focusing on visual function and retinal structure.ResultsForty patients from 35 families were included (ages: 2.5–80.1 years). In patients with a follow-up of >1 year (63%), the mean follow-up time was 12.0 years (range: 2.3–29.2 years). Based on the patient history, symptoms and/or electroretinography, 22 patients (55%) were diagnosed with retinitis pigmentosa (RP), 15 (38%) with Leber congenital amaurosis (LCA) and 3 (8%) with macular dystrophy (MD), the latter being associated with the p.(Ile167_Gly169del) mutation (in compound heterozygosity). MD later developed into a rod-cone dystrophy in one patient. Blindness at initial presentation was seen in the first decade of life in LCA, and in the fifth decade of life in RP. Eventually, 28 patients (70%) reached visual acuity-based blindness (<0.05). Visual field-based blindness (<10°) was documented in 17/25 patients (68%). Five patients (13%) developed Coats-like exudative vasculopathy. Intermediate/posterior uveitis was found in three patients (8%). Cystoid maculopathy was common in RP (9/21; 43%) and MD (3/3; 100%). Macular involvement, varying from retinal pigment epithelium alterations to complete outer retinal atrophy, was observed in all patients.ConclusionBi-allelic CRB1 mutations result in a range of progressive retinal disorders, most of which are generalised, with characteristically early macular involvement. Visual function and retinal structure analysis indicates a window for potential intervention with gene therapy before the fourth decade of life in RP and the first decade in LCA.

Sign in / Sign up

Export Citation Format

Share Document