scholarly journals Unique combination of clinical features in a large cohort of 100 patients with retinitis pigmentosa caused by FAM161A mutations

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Avigail Beryozkin ◽  
Samer Khateb ◽  
Carlos Alberto Idrobo-Robalino ◽  
Muhammad Imran Khan ◽  
Frans P. M. Cremers ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Clinical Features ◽  
Outer Nuclear Layer ◽  
Single Gene ◽  
Fundus Autofluorescence ◽  
Severe Disease ◽  
Visual Fields ◽  
Future Application ◽  
Initial Symptom ◽  
Clinical Records

Abstract FAM161A mutations are the most common cause of autosomal recessive retinitis pigmentosa in the Israeli-Jewish population. We aimed to characterize the spectrum of FAM161A-associated phenotypes and identify characteristic clinical features. We identified 114 bi-allelic FAM161A patients and obtained clinical records of 100 of these patients. The most frequent initial symptom was night blindness. Best-corrected visual acuity was largely preserved through the first three decades of life and severely deteriorated during the 4th–5th decades. Most patients manifest moderate-high myopia. Visual fields were markedly constricted from early ages, but maintained for decades. Bone spicule-like pigmentary changes appeared relatively late, accompanied by nummular pigmentation. Full-field electroretinography responses were usually non-detectable at first testing. Fundus autofluorescence showed a hyper-autofluorescent ring around the fovea in all patients already at young ages. Macular ocular coherence tomography showed relative preservation of the outer nuclear layer and ellipsoid zone in the fovea, and frank cystoid macular changes were very rare. Interestingly, patients with a homozygous nonsense mutation manifest somewhat more severe disease. Our clinical analysis is one of the largest ever reported for RP caused by a single gene allowing identification of characteristic clinical features and may be relevant for future application of novel therapies.

scholarly journals Microglia dynamics in retinitis pigmentosa model: formation of fundus whitening and autofluorescence as an indicator of activity of retinal degeneration

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kenichi Makabe ◽  
Sunao Sugita ◽  
Michiko Mandai ◽  
Yoko Futatsugi ◽  
Masayo Takahashi
Keyword(s):  
Retinitis Pigmentosa ◽  
Retinal Degeneration ◽  
Outer Nuclear Layer ◽  
Fundus Autofluorescence ◽  
Fundus Photography ◽  
Photoreceptor Outer Segments ◽  
Diagnostic Interpretation ◽  
Model Formation ◽  
Thinning Rate

Abstract In patients with retinitis pigmentosa (RP), color fundus photography and fundus autofluorescence (FAF) have been used to estimate the disease progression. To understand the origin and the diagnostic interpretation of the fundus color and FAF, we performed in vivo imaging of fundus color and FAF together with histological analyses of the retinal degeneration process using the RP model mice, rd10. FAF partly represented the accumulation of microglia in the photoreceptor outer segments. Fundus whitening suggested the presence of apoptotic cells, which spatiotemporally preceded increase in FAF. We observed two patterns of FAF localization, arcuate and diffuse, each indicating different pattern of apoptosis, wavy and diffuse, respectively. Diffuse pattern of apoptosis was suppressed in dark-raised rd10 mice, in which outer nuclear layer (ONL) loss was significantly suppressed. The occupancy of FAF correlated with the thinning rate of the ONL. Fractalkine, a microglia chemotactic factor, was detected in apoptotic photoreceptors, suggesting chemokine-induced recruitment of microglia into the ONL, which paralleled with accelerated ONL loss and increased FAF occupancy. Thus, we propose that the degree of photoreceptor apoptosis and the rate of ONL thinning in RP patients might be read from the fundus color and the FAF.

scholarly journals Genetic and Clinical Findings in an Ethnically Diverse Cohort with Retinitis Pigmentosa Associated with Pathogenic Variants in CERKL

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1497
Author(s):  
Susan M. Downes ◽  
Tham Nguyen ◽  
Vicky Tai ◽  
Suzanne Broadgate ◽  
Mital Shah ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Fundus Autofluorescence ◽  
Age At Onset ◽  
Visual Fields ◽  
Case Series ◽  
Clinical Findings ◽  
Fundus Photography ◽  
Presenting Symptoms ◽  
Ceramide Kinase ◽  
Pathogenic Variants

Autosomal recessive retinitis pigmentosa is caused by mutations in over 40 genes, one of which is the ceramide kinase-like gene (CERKL). We present a case series of six patients from six unrelated families diagnosed with inherited retinal dystrophies (IRD) and with two variants in CERKL recruited from a multi-ethnic British population. A retrospective review of clinical data in these patients was performed and included colour fundus photography, fundus autofluorescence (AF) imaging, spectral domain–optical coherence tomography (SD–OCT), visual fields and electroretinogram (ERG) assessment where available. Three female and three male patients were included. Age at onset ranged from 7 years old to 45 years, with three presenting in their 20s and two presenting in their 40s. All but one had central visual loss as one of their main presenting symptoms. Four patients had features of retinitis pigmentosa with significant variation in severity and extent of disease, and two patients had no pigment deposition with only macular involvement clinically. Seven variants in CERKL were identified, of which three are novel. The inherited retinopathies associated with the CERKL gene vary in age at presentation and in degree of severity, but generally are characterised by a central visual impairment early on.

scholarly journals Multimodal Imaging Characteristics of ADRP in a Family with p.Thr58Arg Substituted RHO Mutation

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Misty Ruppert ◽  
John Pyun ◽  
K. V. Chalam ◽  
David Sierpina
Keyword(s):  
Retinitis Pigmentosa ◽  
Multimodal Imaging ◽  
Fundus Autofluorescence ◽  
Visual Fields ◽  
Retinal Dystrophy ◽  
Young Patients ◽  
Photoreceptor Cells ◽  
Wide Field ◽  
Photoreceptor Layer ◽  
Imaging Characteristics

Background. Autosomal dominant retinitis pigmentosa (adRP) is a rare cause of progressive visual impairment in young patients and is frequently a result of RHO gene mutations. p.Thr58Arg rhodopsin mutation leads to misfolding of rhodopsin, subsequent accumulation in the endoplasmic reticulum, and leads to consecutive atrophy of photoreceptor cells through apoptosis. Materials and Methods. We describe multimodal imaging findings in a 58-year-old female with adRP due to a c.173 C > G, p.Thr58Arg rhodopsin mutation (confirmed on genotyping), including ultra-wide-field fundus autofluorescence (UWF-FAF), color scanning laser ophthalmoscopy, structural optical coherence tomography (OCT), OCT-angiography (OCT-A), electroretinography (ERG), and visual field testing (HVF). Additionally, we compare the patient’s phenotypic findings to those of her offspring, who was also affected by adRP. Results. The 58-year-old female and her son with symptoms of nyctalopia and decreased vision showed macular pigmentary changes in a bull’s-eye pattern along with bone spicules in periphery with retinal atrophy. Genotyping confirmed p.Thr58Arg rhodopsin mutation. Wide area of dystrophic retina was noted on UWF-FAF, along with corresponding atrophy of photoreceptor layer on OCT. OCTA revealed complete nonperfusion of the superficial capillary plexus in areas of retinal dystrophy. ERG revealed increased latency and decreased amplitudes; HVF revealed constriction of visual fields consistent with retinal findings. Conclusions. Multimodal imaging is extremely helpful in delineating the extent of retinal dystrophy and comparable to ERG for monitoring of progress in retinitis pigmentosa. Photoreceptor layer thickness (measured with OCT) strongly correlated with ERG and can be used as a secondary surrogate for monitoring the disease progress.

scholarly journals Clinical Phenotype of PDE6B-Associated Retinitis Pigmentosa

2021 ◽  
Vol 22 (5) ◽  
pp. 2374
Author(s):  
Laura Kuehlewein ◽  
Ditta Zobor ◽  
Katarina Stingl ◽  
Melanie Kempf ◽  
Fadi Nasser ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Genetic Testing ◽  
Retinitis Pigmentosa ◽  
Fundus Autofluorescence ◽  
Retinal Disease ◽  
New Drugs ◽  
Autofluorescence Imaging ◽  
Full Field ◽  
Tertiary Referral Center ◽  
The Right

In this retrospective, longitudinal, observational cohort study, we investigated the phenotypic and genotypic features of retinitis pigmentosa associated with variants in the PDE6B gene. Patients underwent clinical examination and genetic testing at a single tertiary referral center, including best-corrected visual acuity (BCVA), kinetic visual field (VF), full-field electroretinography, full-field stimulus threshold, spectral domain optical coherence tomography, and fundus autofluorescence imaging. The genetic testing comprised candidate gene sequencing, inherited retinal disease gene panel sequencing, whole-genome sequencing, and testing for familial variants by Sanger sequencing. Twenty-four patients with mutations in PDE6B from 21 families were included in the study (mean age at the first visit: 32.1 ± 13.5 years). The majority of variants were putative splicing defects (8/23) and missense (7/23) mutations. Seventy-nine percent (38/48) of eyes had no visual acuity impairment at the first visit. Visual acuity impairment was mild in 4% (2/48), moderate in 13% (6/48), and severe in 4% (2/48). BCVA was symmetrical in the right and left eyes. The kinetic VF measurements were highly symmetrical in the right and left eyes, as was the horizontal ellipsoid zone (EZ) width. Regarding the genetic findings, 43% of the PDE6B variants found in our patients were novel. Thus, this study contributed substantially to the PDE6B mutation spectrum. The visual acuity impairment was mild in 83% of eyes, providing a window of opportunity for investigational new drugs. The EZ width was reduced in all patients and was highly symmetric between the eyes, making it a promising outcome measure. We expect these findings to have implications on the design of future PDE6B-related retinitis pigmentosa (RP) clinical trials.

scholarly journals Excision of Greater Superficial Petrosal Nerve Schwannoma Via a Pure Endoscopic Endonasal Approach

2021 ◽  
pp. 014556132110263
Author(s):  
Zhenlin Wang ◽  
Siyuan Zhang ◽  
Yan Qi ◽  
Lianjie Cao ◽  
Pu Li ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Clinical Features ◽  
Middle Cranial Fossa ◽  
Nerve Sheath Tumor ◽  
Endoscopic Endonasal Approach ◽  
Endonasal Approach ◽  
Endoscopic Endonasal ◽  
Greater Superficial Petrosal Nerve ◽  
Clinical Records

Greater superficial petrosal nerve (GSPN) schwannomas are an exceedingly rare nerve sheath tumor. The current literature search was conducted using Medline and Embase database by key search terms. Only 31 cases have been reported in the literature so far. Facial palsy, hearing loss, and xerophthalmia accounted for 48.4% (15), 41.9% (13), and 29% (9) of all cases, respectively. The middle cranial fossa approach was used in all previous reports. A retrospective review of 2 GSPN schwannomas patients treated by endoscopic endonasal approach (EEA) in our center was collected. Clinical records, including clinical features, pre- and postoperative images, surgery, and follow-up information, were reviewed. In all cases, clinical features including facial numbness and headache were found, with tinnitus in case 1, hearing loss, xerophthalmia in case 2. Imaging studies showed a solid mass that originated in the anterior of the petrous bone. Two patients were treated by EEA. Furthermore, no recurrence was found during the follow-up period (15-29 months) in both of the 2 cases after the operation. Complete resection of GSPN schwannomas can be achieved via the pure EEA. Endoscopic endonasal approach for radical removal of tumors is safe and feasible.

Clinical, cellular, and molecular characterisation of cardiac rhabdomyoma in tuberous sclerosis

2021 ◽  
pp. 1-9
Author(s):  
Hamood N. Al Kindi ◽  
Ayman M. Ibrahim ◽  
Mohamed Roshdy ◽  
Besra S. Abdelghany ◽  
Dina Yehia ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Clinical Features ◽  
Tuberous Sclerosis Complex ◽  
Potential Role ◽  
Severe Disease ◽  
Cardiac Rhabdomyoma ◽  
Urgent Surgery ◽  
Pathogenic Mutations ◽  
Personalised Treatment

Abstract Background: Rhabdomyoma is the most common cardiac tumour in children. It is usually associated with tuberous sclerosis complex caused by mutations in TSC-1 or TSC-2 genes. This tumour typically regresses by unknown mechanisms; however, it may cause inflow or outflow obstruction that necessitates urgent surgery. Here we investigate the clinical features and the genetic analysis of patients with tuberous sclerosis complex presenting with large rhabdomyoma tumours. We also investigate the potential role of autophagy and apoptosis in the pathogenesis of this tumour. Methods: All the patients with cardiac rhabdomyoma referred to Aswan Heart Centre from 2010 to 2018 were included in this study. Sanger sequencing was performed for coding exons and the flanking intronic regions of TSC1 and TSC2 genes. Histopathological evaluation, immunohistochemistry, and western blotting were performed with P62, LC3b, caspase3, and caspase7, to evaluate autophagic and apoptotic signaling. Results: Five patients were included and had the clinical features of tuberous sclerosis complex. Three patients, who were having obstructive tumours, were found to have pathogenic mutations in TSC-2. The expression of two autophagic markers, P62 and LC3b, and two apoptotic markers, caspase3 and caspase7, were increased in the tumour cells compared to normal surrounding myocardial tissue. Conclusion: All the patients with rhabdomyoma were diagnosed to have tuberous sclerosis complex. The patients who had pathogenic mutations in the TSC-2 gene had a severe disease form necessitating urgent intervention. We also demonstrate the potential role of autophagy and apoptosis as a possible mechanism for tumourigenesis and regression. Future studies will help in designing personalised treatment for cardiac rhabdomyoma.

Clinical features, pathogenesis and treatment of long-haul COVID‑19 impact on nervous system

2021 ◽  
pp. 14-22
Author(s):  
A. N. Barinov ◽  
L. S. Moshkhoeva ◽  
E. V. Parkhomenko ◽  
E. V. Emikh ◽  
I. P. Yastrebtseva
Keyword(s):  
Nervous System ◽  
Cognitive Impairment ◽  
Cognitive Therapy ◽  
Clinical Features ◽  
Severe Disease ◽  
Vitamin B ◽  
Difficulty Breathing ◽  
Current Outbreak ◽  
Ethylmethylhydroxypyridine Succinate

The current outbreak of coronavirus SARS-CoV‑2 (COVID-19) has raised great concern worldwide, but its impact on nervous system still needs more investigation. Thirty per cent of symptomatic patients with COVID‑19 will have symptoms that last longer than the typical two weeks, 10 % have symptoms longer than 3 months and this is called ‘long-COVID’. These symptoms affect not only people with severe disease, but also those with milder cases. Many long-haulers experience the same symptoms they had during their initial fight with COVID‑19, such as fatigue, cognitive impairment (or brain fog), difficulty breathing, headache, depression, insomnia and loss of the sense of taste and\or smell. Treatment of those complications with citicoline, ethylmethylhydroxypyridine succinate and vitamin B improves these symptoms in patients but most of them also need cognitive therapy for dehypochondrisation.

scholarly journals A 13-year-old Female with Bardet- Biedl Syndrome - A Case Report

2015 ◽  
Vol 26 (1) ◽  
pp. 31-34
Author(s):  
Syed Nesar Ahmed ◽  
Md Abu Shahin ◽  
Romal Chowdhury ◽  
Alamgir Mustak Ahammad ◽  
Md Nahiduzzaman Shazzad ◽  
...  
Keyword(s):  
Case Report ◽  
Retinitis Pigmentosa ◽  
Rare Disease ◽  
Clinical Features ◽  
Night Blindness ◽  
Learning Difficulties ◽  
Laboratory Findings ◽  
Bardet Biedl Syndrome

Bardet Biedl syndrome is a rare disease. A case report is presented here where a 13 years old girl presented with obesity, night blindness, learning difficulties and polydactyly. Obesity and night blindness started from since childhood. Her milestones of development were normal but having some learning difficulties. Her parents are healthy as well as her siblings. On examination she looks apathy, extreme obese, having polydactyly and retinitis pigmentosa and high B.P. On laboratory findings there is only dyslipidaemia. On the basis of clinical features she was diagnosed as a case of Bardet-Biedl syndrome.Bangladesh J Medicine Jan 2015; 26 (1) : 31-34

scholarly journals Epidemiology and clinical features of coronavirus disease 2019 in children

2020 ◽  
Vol 63 (4) ◽  
pp. 125-132 ◽  
Author(s):  
Soo-Han Choi ◽  
Han Wool Kim ◽  
Ji-Man Kang ◽  
Dong Hyun Kim ◽  
Eun Young Cho
Keyword(s):  
Infectious Disease ◽  
Children And Adolescents ◽  
Clinical Features ◽  
Severe Disease ◽  
Respiratory Illness

Coronavirus disease-2019 (COVID-19), which started in Wuhan, China, in December 2019 and declared a worldwide pandemic on March 11, 2020, is a novel infectious disease that causes respiratory illness and death. Pediatric COVID-19 accounts for a small percentage of patients and is often milder than that in adults; however, it can progress to severe disease in some cases. Even neonates can suffer from COVID-19, and children may spread the disease in the community. This review summarizes what is currently known about COVID-19 in children and adolescents.

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