Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation

Purpose By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). Methods We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. Results We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. Conclusion The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS

Unilateral Coats'-like disease and an intragenic deletion in the TERC gene: A case report

We report a case of a 25-year-old woman with unilateral Coats'-like disease. Her brother was previously diagnosed with an autosomal dominant form of dyskeratosis congenita. Genetic testing was performed by screening the TERC gene for mutations and identified heterozygosity for the n.68_124del mutation. Our case demonstrates that the exudative retinopathy seen in Coats'-like disease can be caused by mutations in a telomere-capping gene TERC as a part of the dyskeratosis congenita spectrum without other systemic involvement. This is an interesting case that illustrates that retinal Coats'-like involvement can be the first manifestation of dyskeratosis congenita.status: publishe

Ophthalmological examination in neurofibromatosis type 1: a long-term retrospective analysis

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Peculiar fundus abnormalities and pathognomonic electrophysiological findings in a 14-month-old boy with NR2E3 mutations

Enhanced S-cone syndrome is a rare, slowly progressive autosomal recessively inherited retinal degeneration related to mutations in the NR2E3 gene. Patients often present with night blindness, visual loss and visual field abnormalities. Patients with enhanced S-cone syndrome exhibit a variable clinical phenotype associated with various degrees of pigmentary changes and foveal schisis. We report a 14-month-old boy with an unusual funduscopic appearance. The diagnosis of enhanced S-cone syndrome was suggested by the uniquely abnormal electroretinographic pattern and was confirmed by the finding of homozygous NR2E3 mutations

Ophthalmic Outcome in a Belgian Cohort of Cystinosis Patients Treated with a Compounded Preparation of Cysteamine Eye Drops: Retrospective Analysis

INTRODUCTION: Treatment of the anterior segment problems in cystinosis is challenging as oral cysteamine is ineffective in the treatment of corneal problems because of its avascular structure. Although cysteamine eye drops have been formulated to counter this issue, the stability of cysteamine in these off-licensed formulations and treatment compliance are major problems. The aim of this retrospective study was to determine the efficacy of a compounded preparation of aqueous 0.5% cysteamine eye drops in the management of corneal complications of cystinosis. METHODS: Data of patients attending the multidisciplinary cystinosis clinic at the University Hospitals Leuven, Belgium between January 2015 and December 2018 were analyzed. All cystinosis patients were treated with the compounded preparation of aqueous 0.5% cysteamine eye drops and oral cysteamine. RESULTS: A total of 12 patients were treated with the compounded preparation of aqueous 0.5% cysteamine eye drops, of whom 75% were aged > 18 years (n = 9). The mean instillation frequency of the cysteamine eye drops was 3.3 drops/eye per day, and the mean number of hospital visits was two per year. All patients showed photophobia, > 30% corneal infiltration, blepharospasm, eye pain and conjunctival hyperemia during the study period. None of these symptoms improved with treatment with aqueous compounded 0.5% cysteamine eye drops. The corneal cystine crystal score was ≥ 2 in all patients at the last  visit. CONCLUSION: Treatment with the compounded preparation of aqueous 0.5% cysteamine eye drops, combined with oral cysteamine, was not effective in reducing corneal cystine crystal deposition and other ocular symptoms in these patients with cystinosis. FUNDING: Recordati Rare Diseases.status: publishe

Choroidal Thickness of the Papillomacular Region in Young Healthy Individuals

PURPOSE: To characterize the choroidal thickness of the papillomacular region in young healthy individuals using spectral-domain optical coherence tomography (SD-OCT). METHODS: Papillary and macular SD-OCT scans were obtained using an enhanced depth imaging mode. Digital retinography was used to assess any overlapping areas and to determine the papillomacular region. Spearman's correlations were used to explore the relationship between the different regional choroidal thicknesses. RESULTS: Sixty-three volunteers aged 21.6 ± 1.1 years were included. There was a significant asymmetry in choroidal thickness throughout the 10-mm length model (p < 0.001). While the choroid was shown to thicken as the distance from the optic disc increased (p < 0.001), each of the 500-µm blocks of the papillomacular region were significantly thinner than their nasal counterparts (p < 0.02 in all pairwise comparisons). CONCLUSION: In young healthy individuals, the choroid under the papillomacular region appears to be thinner than in other areas. These differences could relate to specificities of the retina overlying this region.status: publishe

Posterior amorphous corneal dystrophy caused by a de novo deletion

We present a newborn diagnosed with posterior amorphous corneal dystrophy (PACD). PACD is a rare disorder with partial or complete posterior lamellar corneal opacification. Genetic screening showed a deletion of chromosome 12q21.33-q22 containing the identified four small leucine-rich proteoglycans (SLRP's) associated with this particular dystrophy. Neither parents were carrier of the deletion. To our knowledge, this is the first report of a de novo mutation causing PACD.peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=iopg20status: publishe

Ophthalmological findings in congenital CMV-infection: when to screen, when to treat?

Cytomegalovirus (CMV) is the leading cause of known congenital viral infections. Approximately 90% of congenitally infected newborns exhibit no clinical abnormalities at birth. In 5% to 15%, a wide spectrum of clinical signs is present at birth. Ophthalmological signs are seen in a large percentage of symptomatic patients but rarely in otherwise asymptomatic infants. Chorioretinitis, optic atrophy, and cortical visual impairment are the most frequent causes of visual problems in congenitally infected infants. There is no clear consensus in the literature on screening or treatment modalities concerning the ophthalmological aspects of congenital CMV. Further prospective studies are needed to set up guidelines for ophthalmological screening and treatment of infants with congenital CMV.status: publishe

Negative commercial screening test for paraneoplastic antibodies in a case of opsoclonus

International audienc

Choroidal abnormalities in café-au-lait syndromes: A new differential diagnostic tool ?

The best known café-au-lait syndrome is neurofibromatosis type 1 (NF1). Legius syndrome (LS) is another, rarer syndrome with café-au-lait macules (CALMs). In young patients their clinical picture is often indistinguishable. We investigated the presence of choroidal abnormalities in syndromes with CALMs as a candidate tool for a more efficient diagnosis. 34 patients with NF1 (14 with a truncating mutation, 14 with a non-truncating mutation and 6 with unknown mutation) and 11 patients with LS. All patients underwent an ophthalmological examination. Infrared images were performed. Choroidal nodules were diagnosed in 65% of the NF1 group. 71% of NF1 patients with a truncating mutation and 50% of patients with a non-truncating mutation were found to have nodules. Choroidal nodules were seen in 18% of the LS patients, never more than one nodule/eye was detected in this group. Choroidal nodules are more abundantly present in NF1 genotypes with truncating mutations. In contrast, the number of choroidal nodules in LS is comparable with their presence in healthy individuals. Especially at an early age, when the clinical picture is incomplete, the detection of choroidal nodules are of diagnostic value, and help in an appropriate genetic counselling and follow up. These results support the suggestion to include choroidal nodules to the diagnostic criteria for NF1.status: publishe