An Update on the Ophthalmologic Features in the Phakomatoses

Abdolrahimzadeh, Solmaz; Plateroti, Andrea Maria; Recupero, Santi Maria; Lambìase, Alessandro

doi:10.1155/2016/3043026

Cited by 31 publications

(21 citation statements)

References 109 publications

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“…Diagnostic ophthalmological findings comprise multiple retinal hamartomas as a major criterion and multiple achromic patches as minor ones [ 4 ]. They have been reported in 39–50% of TSC patients and may be found at any age [ 1 , 29 , 30 ]. In the group of ‘early TSC diagnosis’ we found multiple retinal hamartomas in 5 (5/82, 6.1%) and achromic patches in 2 (2/82, 2.4%) patients.…”

Section: Discussionmentioning

confidence: 99%

Early diagnosis of tuberous sclerosis complex: a race against time. How to make the diagnosis before seizures?

Słowińska

Jóźwiak

Peron

et al. 2018

Orphanet J Rare Dis

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BackgroundTuberous sclerosis complex (TSC) is a genetic disorder with an incidence of 1:6000 live births and associated with the development of benign tumors in several organs. It is also characterized by high rates of neurological and neuropsychiatric abnormalities, including epilepsy affecting 70–90% of patients and being one of the major risk factors of intellectual disability. The first seizures in TSC patients appear usually between the 4th and the 6th months of life. Recent studies have shown the beneficial role of preventative antiepileptic treatment in TSC patients, with the possibility for improvement of cognitive outcome. Moreover, European recommendations suggest early introduction of Vigabatrin if ictal discharges occur on EEG recordings, with or without clinical manifestation.The aim of this study was to define the most useful approach to make the diagnosis of TSC before seizure onset (before age 4th months), in order to start early EEG monitoring with possible preventative treatment intervention.MethodsWe performed a retrospective review of children who were suspected of having TSC due to single or multiple cardiac tumors as the first sign of the disease. We analyzed the medical records in terms of conducted clinical tests and TSC signs, which were observed until the end of the 4th month of age. Subsequently, we described the different clinical scenarios and recommendations for early diagnosis.Results82/100 children were diagnosed with TSC within the first 4 months of life. Apart from cardiac tumors, the most frequently observed early TSC signs were subependymal nodules (71/100, 71%), cortical dysplasia (66/100, 66%), and hypomelanotic macules (35/100, 35%). The most useful clinical studies for early TSC diagnosis were brain magnetic resonance imaging (MRI), skin examination and echocardiography. Genetic testing was performed in 49/100 of the patients, but the results were obtained within the first 4 months of life in only 3 children.ConclusionsEarly diagnosis of TSC, before seizure onset, is feasible and it is becoming pivotal for epilepsy management and improvement of cognitive outcome. Early TSC diagnosis is mostly based on clinical signs. Brain MRI, echocardiography, skin examination and genetic testing should be performed early in every patient suspected of having TSC.

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Section: Discussionmentioning

confidence: 99%

Early diagnosis of tuberous sclerosis complex: a race against time. How to make the diagnosis before seizures?

Słowińska

Jóźwiak

Peron

et al. 2018

Orphanet J Rare Dis

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“… 3 , 4 More recently, abnormalities in the retinal and choroidal vasculature have been appreciated with an estimated prevalence between 60% and 100% of persons with NF1. 5 – 11 Retinal capillaries and feeder vessels appear tortuous and disorganized and are often found in close proximity to choroidal abnormalities. Similarly, Shields et al 12 , 13 have identified an association between retinal vasoproliferative tumors (RVPT) and NF1, which is often associated with visual disturbances.…”

mentioning

confidence: 99%

Neurofibromin Deficiency Induces Endothelial Cell Proliferation and Retinal Neovascularization

Zhang

Hudson

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PurposeNeurofibromatosis type 1 (NF1) is the result of inherited mutations in the NF1 tumor suppressor gene, which encodes the protein neurofibromin. Eye manifestations are common in NF1 with recent reports describing a vascular dysplasia in the retina and choroid. Common features of NF1 retinopathy include tortuous and dilated feeder vessels that terminate in capillary tufts, increased endothelial permeability, and neovascularization. Given the retinal vascular phenotype observed in persons with NF1, we hypothesize that preserving neurofibromin may be a novel strategy to control pathologic retinal neovascularization.MethodsNf1 expression in human endothelial cells (EC) was reduced using small hairpin (sh) RNA and EC proliferation, migration, and capacity to form vessel-like networks were assessed in response to VEGF and hypoxia. Wild-type (WT), Nf1 heterozygous (Nf1+/−), and Nf1flox/+;Tie2cre pups were subjected to hyperoxia/hypoxia using the oxygen-induced retinopathy model. Retinas were analyzed quantitatively for extent of retinal vessel dropout, neovascularization, and capillary branching.ResultsNeurofibromin expression was suppressed in response to VEGF, which corresponded with activation of Mek-Erk and PI3-K-Akt signaling. Neurofibromin-deficient EC exhibited enhanced proliferation and network formation in response to VEGF and hypoxia via an Akt-dependent mechanism. In response to hyperoxia/hypoxia, Nf1+/− retinas exhibited increased vessel dropout and neovascularization when compared with WT retinas. Neovascularization was similar between Nf1+/− and Nf1flox/+;Tie2cre retinas, but capillary drop out in Nf1flox/+;Tie2cre retinas was significantly reduced when compared with Nf1+/− retinas.ConclusionsThese data suggest that neurofibromin expression is essential for controlling endothelial cell proliferation and retinal neovascularization and therapies targeting neurofibromin-deficient EC may be beneficial.

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“…Bu nedenle erişkinlerde NF-1'in en sık görülen bulgusudur. Beş yaşında %22, 20 yaş ve üzerinde %96 oranında görüldüğü-nü bildirmiştir [13] . Bir çalışmada 369 vakada Lisch nodülü sıklığı %63.2 olarak rapor etmişlerdir [14] .…”

Section: Discussionunclassified

“…NF-1'li olgularda en sık görülen beyin tümörü optik gliomlardır. Çoğu asemptomatiktir [13] . Duffner ve ark.…”

Section: Discussionunclassified

Neurofibromatosis type-1: Evaluation of 49 cases

Çarman¹

2017

Haydarpasa Numune Med J

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An Update on the Ophthalmologic Features in the Phakomatoses

Cited by 31 publications

References 109 publications

Early diagnosis of tuberous sclerosis complex: a race against time. How to make the diagnosis before seizures?

Early diagnosis of tuberous sclerosis complex: a race against time. How to make the diagnosis before seizures?

Neurofibromin Deficiency Induces Endothelial Cell Proliferation and Retinal Neovascularization

Neurofibromatosis type-1: Evaluation of 49 cases

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