Pathogenic NR2F1 variants cause a developmental ocular phenotype recapitulated in a mutant mouse model.

Pathogenic NR2F1 variants cause a rare autosomal dominant neurodevelopmental disorder referred to as the Bosch-Boonstra-Schaaf Optic Atrophy Syndrome. Although visual loss is a prominent feature seen in affected individuals, the molecular and cellular mechanisms contributing to visual impairment are still poorly characterized. We conducted a deep phenotyping study on a cohort of 22 individuals carrying pathogenic NR2F1 variants to document the neurodevelopmental and ophthalmological manifestations, in particular the structural and functional changes within the retina and the optic nerve, which have not been detailed previously. The visual impairment became apparent in early childhood with small and/or tilted hypoplastic optic nerves observed in 10 cases. High-resolution optical coherence tomography imaging confirmed significant loss of retinal ganglion cells with thinning of the ganglion cell layer, consistent with electrophysiological evidence of retinal ganglion cells dysfunction. Interestingly, for those individuals with available longitudinal ophthalmological data, there was no significant deterioration in visual function during the period of follow-up. Diffusion tensor imaging tractography studies showed defective connections and disorganization of the extracortical visual pathways. To further investigate how pathogenic NR2F1 variants impact on retinal and optic nerve development, we took advantage of an Nr2f1 mutant mouse disease model. Abnormal retinogenesis in early stages of development was observed in Nr2f1 mutant mice with decreased retinal ganglion cell density and disruption of retinal ganglion cell axonal guidance from the neural retina into the optic stalk, accounting for the development of optic nerve hypoplasia. The mutant mice showed significantly reduced visual acuity based on electrophysiological parameters with marked conduction delay and decreased amplitude of the recordings in the superficial layers of the visual cortex. The clinical observations in our study cohort, supported by the mouse data, suggest an early neurodevelopmental origin for the retinal and optic nerve head defects caused by NR2F1 pathogenic variants, resulting in congenital vision loss that seems to be non-progressive. We propose NR2F1 as a major gene that orchestrates early retinal and optic nerve head development, playing a key role in the maturation of the visual system.

Macular Hole After Poppers (Alkyl Nitrate) Inhalation in a Child.

The authors present the first case of macular hole (MH) after a single inhalation of poppers. A 13-year-old girl presented with vision loss in the left eye (OS). Pediatric and neurology exams were normal. Funduscopy revealed bilateral papilledema and yellow foveal spot OS. Optic neuritis was diagnosed and treated. Due to foveal alteration, optical coherence tomography was performed, and MH was diagnosed. Twenty-three-gauge pars plana vitrectomy, peeling of the internal limiting membrane, and SF6 exchange were performed. Postoperatively, vision restoration and MH closure were observed. Although MH mechanism in the poppers context is unknown, the classic surgery is effective. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:897-900.].

Hipertensión intracraneal idiopática familiar: a propósito de dos casos pediátricos / Familial idiopathic intracranial hypertension: two paediatric case reports

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