RESUMO
Certain combinations of common variants in exon 3 of OPN1LW and OPN1MW, the genes encoding the apo-protein of the long- and middle-wavelength sensitive cone photoreceptor visual pigments in humans, induce splicing defects and have been associated with dyschromatopsia and cone dysfunction syndromes. Here we report the identification of a novel exon 3 haplotype, G-C-G-A-T-T-G-G (referring to nucleotide variants at cDNA positions c.453, c.457, c.465, c.511, c.513, c.521, c.532, and c.538) deduced to encode a pigment with the amino acid residues L-I-V-V-A at positions p.153, p.171, p.174, p.178, and p.180, in OPN1LW or OPN1MW or both in a series of seven patients from four families with cone dysfunction. Applying minigene assays for all observed exon 3 haplotypes in the patients, we demonstrated that the novel exon 3 haplotype L-I-V-V-A induces a strong but incomplete splicing defect with 3-5% of residual correctly spliced transcripts. Minigene splicing outcomes were similar in HEK293 cells and the human retinoblastoma cell line WERI-Rb1, the latter retaining a cone photoreceptor expression profile including endogenous OPN1LW and OPN1MW gene expression. Patients carrying the novel L-I-V-V-A haplotype presented with a mild form of Blue Cone Monochromacy or Bornholm Eye Disease-like phenotype with reduced visual acuity, reduced cone electroretinography responses, red-green color vision defects, and frequently with severe myopia.
Assuntos
Defeitos da Visão Cromática , Opsinas de Bastonetes/genética , Defeitos da Visão Cromática/genética , Defeitos da Visão Cromática/metabolismo , Éxons/genética , Células HEK293 , Haplótipos , Humanos , Células Fotorreceptoras Retinianas Cones/metabolismo , Opsinas de Bastonetes/metabolismoRESUMO
PURPOSE: Nonsyndromic autosomal recessive optic atrophy (arOA) is extremely rare and its existence was disputed until a locus, optic atrophy 6 (OPA6), was mapped to 8q. Recently, a second locus, OPA7, was found on 11q in several families from North Africa, with one presumably ancestral mutation of transmembrane protein 126A (TMEM126A). Here we report an independently ascertained large consanguineous family of Moroccan descent with three siblings affected with nonsyndromic arOA. METHODS: Assuming autosomal recessive inheritance, we identified a locus on 11q with homozygosity mapping, with a multipoint logarithm of the odds score of 3.84, and sequenced two candidate genes. Direct sequencing of the complete coding sequence of TMEM126A revealed mutation p.Arg55X, homozygous in all affected siblings and heterozygous in both unaffected parents. RESULTS: This mutation was identical to that recently reported in families from North Africa, consistent with a single ancestral origin. In contrast to the recently reported patients, however, the siblings reported in this study had a relatively mild clinical course, with sudden onset in adolescence in the proband. Interestingly, the proband, but not the other affected siblings, had sensory-motor axonal neuropathy with electrophysiological data strongly suggestive of focal demyelinating abnormalities. An unaffected sibling had transient loss of vision after exercise, i.e., Uhthoff's sign of optic neuropathy, and was found to be a heterozygous carrier of the mutation. CONCLUSIONS: Our results confirm genetic heterogeneity in arOA, illustrate clinical variability between families with the p.Arg55X mutation including the description of a mild phenotype in a heterozygote, and underscore the implication of mitochondrial proteins in optic and peripheral neuropathy.
Assuntos
Proteínas de Membrana/genética , Atrofia Óptica/genética , Adolescente , Adulto , Cromossomos Humanos Par 11 , Consanguinidade , Genes Recessivos , Loci Gênicos , Heterozigoto , Homozigoto , Humanos , Atrofia Óptica/etnologia , Linhagem , Análise de Sequência de DNA , IrmãosRESUMO
Ocular neuromyotonia (ONM) is characterized by episodes of binocular diplopia usually triggered by an eye movement requiring contraction of the affected extraocular muscle. It consists of an involuntary, sometimes painful contraction of one or more extraocular muscles. It is most often secondary to radiotherapy of the para-sellar region, although other aetiologies have been reported. Some cases do not have a clearly identified aetiology and are classified as idiopathic. Most cases of ONMs are unilateral but bilateral ONMs have also been described.1-4 We report a case of left ONM in a 55-year-old female patient, several weeks after simultaneous surgical resection of two meningiomas, situated on the right side (Simpson II). The particularity of this case is linked to its puzzling presentation, its similarity with spasm of the near reflex and the putative mechanism through which surgery might have precipitated the symptoms.
Assuntos
Síndrome de Isaacs , Diplopia/diagnóstico , Diplopia/etiologia , Movimentos Oculares , Feminino , Humanos , Síndrome de Isaacs/diagnóstico , Síndrome de Isaacs/etiologia , Pessoa de Meia-Idade , Músculos Oculomotores/cirurgia , Nervo OculomotorRESUMO
Purpose: Amblyopia is a major health problem with an estimated 2% to 4% of the population affected. Screening combined with corrective measures, such as correction of refractive error and occlusion of the dominant eye, could reduce this prevalence. A new pediatric vision scanner, the blinq (Rebion, Boston, MA), studies the foveolar quality of fixation of each eye during binocular viewing. Based on the initial premise that poor quality foveolar or non-foveolar fixation is indicative of strabismus and, potentially of amblyopia, this study evaluates the effectiveness of the blinq screening device in detecting these two conditions compared to a standard ophthalmic examination (Gold Standard) based on the recommendations of the American Association for Pediatric Ophthalmology and Strabismus. Material and Methods: A prospective study was performed on a total of 101 children between 2 and 8 years of age. These children were offered a test by the blinq screening device before a standard ophthalmological examination in the ophthalmology department of the Erasmus Hospital in Brussels, Belgium. The two tests were then compared. Results: In a pediatric population heightened with amblyopia and strabismus (prevalence of 33.4%) and based on the Gold Standard Examination, the blinq device showed a specificity of 73.1% (95% confidence interval [CI] = 60.9%-83.2%) with a sensitivity of 91.2% (95% CI = 76.3%-98.1) to detect these conditions. The positive and negative predictive values were 63.3% (95% CI = 53.4%-72.2%) and 94.2% (95% CI = 84.6%-98%) respectively. The positive likelihood ratio (LR+) was 3.39 (95% CI = 2.26-5.11) for a negative likelihood ratio of 0.12 (95% CI = 0.04-0.36). Conclusions: The blinq device has good sensitivity, but insufficient specificity to be used alone in the first line of screening. Whereas other devices on the market detect risk factors that may lead to amblyopia, the blinq pediatric vision scanner detects poor foveolar fixation and strabismus, giving it a potential advantage in sensitivity to directly detect strabismus, including microstrabismus. The blinq does not detect refractive abnormalities, however, and will therefore need to be improved in the future to be used alone in pediatric vision screening. Translational Relevance: The blinq device detects visual axis alignment abnormalities with potential impact in the early detection of strabismus and subsequent associated amblyopia.
Assuntos
Ambliopia , Estrabismo , Seleção Visual , Ambliopia/diagnóstico , Ambliopia/epidemiologia , Criança , Humanos , Estudos Prospectivos , Sensibilidade e Especificidade , Estrabismo/diagnósticoRESUMO
There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis. Paraclinical tests can also be applied retrospectively on stored samples and historical brain or retinal scans, which will be useful for future validation studies. Our criteria have the potential to reduce the risk of misdiagnosis, provide information on optic neuritis disease course that can guide future treatment trial design, and enable physicians to judge the likelihood of a need for long-term pharmacological management, which might differ according to optic neuritis subgroups.
Assuntos
Esclerose Múltipla , Neuromielite Óptica , Neurite Óptica , Humanos , Estudos Retrospectivos , Neurite Óptica/diagnóstico , Neuromielite Óptica/diagnóstico , Esclerose Múltipla/complicações , Autoanticorpos , Aquaporina 4RESUMO
Background: Knobloch syndrome (OMIM 267750) is a rare autosomal recessive disorder due to genetic defects in the COL18A1 gene. The triad of high myopia, occipital defect, vitreoretinal degeneration has been described as pathognomonic for this condition. Patients with Knobloch syndrome have also extraocular problems as brain and kidney malformations. High genetic and phenotypic variation has been reported in the affected patients.Materials and Methods: Here we provide detailed clinical description of 3 individuals with Knobloch syndrome. Ocular examination and fundus imaging have been performed. Detailed information about systemic conditions has been provided.Results: Mutations in COL18A1 were identified in all three patients. Patient 1 had congenital hip dislocation and patient 2 had renal atrophy, cardiac insufficiency and difficult skin healing.Conclusions: With this report we add to the clinical and genetic knowledge of this rare condition.
Assuntos
Colágeno Tipo XVIII/genética , Encefalocele/patologia , Mutação , Degeneração Retiniana/patologia , Descolamento Retiniano/congênito , Adolescente , Pré-Escolar , Encefalocele/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Degeneração Retiniana/genética , Descolamento Retiniano/genética , Descolamento Retiniano/patologiaRESUMO
We report the clinical and radiologic features of a 31-year-old woman who suffered incongruous binasal and bitemporal visual field defects and severe sudden visual loss due to hypoperfusion of bilateral lateral geniculate bodies following anaphylactic shock induced by 500 mg amoxicillin per os. Complete neuroophthalmologic examinations were performed regularly for visual acuity, color vision, pupillary reflexes, and visual fields. Additional testing was performed by means of MR imaging of the brain and CSF analysis. Follow-up was performed for 12 months. Vision loss was acute and severe, its onset bilateral and simultaneous. The patient recovered visual acuity of 1.0 within 7 weeks. Color vision was abnormal in both eyes but gradually improved to normal. Visual fields were characterized by incongruous binasal and bitemporal defects, but they reduced progressively. Cerebral MR imaging confirmed the presence of symmetrical lesions confined exclusively within both lateral geniculate bodies. These lesions were best seen on T1-weighted and fluid-attenuated inversion recovery images as high-signal-intensity areas suggestive of hemorrhagic ischemia. CSF analysis was normal and aseptic. Blood tests and cultures excluded any microbial infection. We conclude that shock may induce a bilateral isolated ischemia of the lateral geniculate bodies, resulting in incongruous binasal and bitemporal visual field defects and severe visual loss. MR imaging is the optimal imaging technique to confirm the diagnosis and for follow-up.
Assuntos
Amoxicilina/efeitos adversos , Anafilaxia/induzido quimicamente , Cegueira Cortical/etiologia , Isquemia Encefálica/etiologia , Hipersensibilidade a Drogas/complicações , Corpos Geniculados/irrigação sanguínea , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Adulto , Amoxicilina/uso terapêutico , Anafilaxia/complicações , Cegueira Cortical/diagnóstico , Isquemia Encefálica/diagnóstico , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiologia , Diagnóstico Diferencial , Dominância Cerebral/fisiologia , Feminino , Corpos Geniculados/patologia , Humanos , Giro Para-Hipocampal/irrigação sanguínea , Giro Para-Hipocampal/patologia , Campos Visuais/efeitos dos fármacosRESUMO
Leber hereditary optic neuropathy is a well-known mitochondrial disorder that leads to bilateral subacute visual failure. Although visual impairment is often the sole clinical feature, additional and severe neurologic abnormalities also have been documented for this disease. We report on a 13-year-old boy who has presented with severe visual failure since early childhood in a context of prematurity. In the first years of his life, clinical features included delayed psychomotor development and ataxia. The clinical presentation, which was initially attributed to prematurity, worsened thereafter, and the child developed acute neurologic degradation with the typical radiological findings of Leigh syndrome. The mitochondrial DNA point mutation 11778G>A was identified in the ND4 gene. The probable influence of environmental background on clinical expression of Leber optic neuropathy, particularly those of prematurity and oxygen therapy, is discussed in our manuscript.
Assuntos
Senilidade Prematura/genética , DNA Mitocondrial/genética , Amaurose Congênita de Leber/genética , Mutação/genética , Adolescente , Senilidade Prematura/complicações , Encéfalo/patologia , Humanos , Amaurose Congênita de Leber/complicações , Imageamento por Ressonância Magnética , MasculinoAssuntos
Oftalmopatias Hereditárias/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Mutação de Sentido Incorreto , Miopia/genética , Cegueira Noturna/genética , Receptores de Glutamato/genética , Adulto , Consanguinidade , Eletrorretinografia , Éxons/genética , Oftalmopatias Hereditárias/diagnóstico , Oftalmopatias Hereditárias/fisiopatologia , Feminino , Seguimentos , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Humanos , Masculino , Miopia/diagnóstico , Miopia/fisiopatologia , Cegueira Noturna/diagnóstico , Cegueira Noturna/fisiopatologia , Linhagem , Retina/fisiopatologiaRESUMO
There are five possible ocular signs or complaints of a life or sight threatening neuro-ophthalmological condition: diplopia, isolated anisocoria, transient visual loss, severe pain in head or neck (with or without photophobia) and oscillopsia/nystagmus. In this review, the ocular signs and symptoms of neuro-ophthalmological emergencies are described together with their practical work-up and the risks associated with missing the diagnosis. Concerning diplopia, the associated signs pointing to a possible threatening condition are emphasized. Six focus points resuming core messages are displayed throughout this review.
Assuntos
Emergências , Neurologia , Oftalmologia , Transtornos da Visão , Humanos , Transtornos da Visão/complicações , Transtornos da Visão/diagnóstico , Transtornos da Visão/terapiaRESUMO
Eye disorders are frequently associated with renal diseases, mostly linked to underlying causes such as hypertension, diabetes or autoimmune diseases. Conversely, advanced uraemic states may also lead to progressive vision impairment. The present report concerns a 50-year-old patient who presented with a bilateral, painless, progressive vision loss, a moderate systemic inflammation and chronic renal failure due to hypertension nephrosclerosis. Steroids were given and haemodialysis was initiated, resulting in vision improvement. At 4 months later when the steroids were stopped, the patient developed dyspnoea, cough, fever and fatigue of unclear origin. A lung biopsy showed non-caseating granuloma consistent with pulmonary sarcoidosis. Re-challenge with steroids rapidly improved the respiratory disease. Ophthalmological examinations performed early and later in the course excluded anterior ischaemic optic neuropathy and ocular manifestations of sarcoidosis, leading to a diagnosis of uraemic optic neuropathy. This rare ophthalmological disorder should be promptly recognised since haemodialysis and steroid therapy are highly effective.
RESUMO
It is well known that refractive anomalies play a prominent role in the genesis of amblyopia. The current aim of early visual screening is to look for these refractive anomalies along with strabismus and media opacities. This update reviews the frequency of refractive anomalies in the preschool-aged population, their amblyogenic potential, and the different methods of refractive screening, including the required equipment, costs, and diagnostic performance.
Assuntos
Erros de Refração/diagnóstico , Seleção Visual/métodos , Ambliopia/etiologia , Pré-Escolar , Humanos , Lactente , Erros de Refração/complicaçõesRESUMO
Congenital stationary night blindness (CSNB) is a group of rare, non-progressive conditions of the retina characterized by abnormal rod function causing impaired night vision. Among them, the Schubert-Bornschein subgroup, itself divided into a complete and an incomplete form, is characterized by a specific electrophysiological pattern. Complete, Schubert-Bornschein CSNB is usually transmitted as a monogenic trait, and most familial cases result from mutations of the NYX gene located on the X chromosome. We report a very rare family with consanguineous, first-cousin parents, where a son and a daughter are affected with this condition, indicating autosomal recessive inheritance. As the family was too small for genome-wide linkage, we considered several candidate loci, including the sidekick SDK1 and SDK2 genes. The latter determine lamina-specific connectivity in the retina, a histological substrate of the ON pathway implicated in complete, Schubert-Bornschein CSNB. Although linkage was excluded in our family, observations like the present one may lead to the identification of a new molecular cause for this condition.