Insights into Novel Choroidal and Retinal Clinical Signs in Neurofibromatosis Type 1

Abstract

Neurofibromatosis type 1 (NF1) is a rare inherited neurocutaneous disorder with a major impact on the skin, nervous system and eyes. The ocular diagnostic hallmarks of this disease include iris Lisch nodules, ocular and eyelid neurofibromas, eyelid café-au-lait spots and optic pathway gliomas (OPGs). In the last years, new manifestations have been identified in the ocular district in NF1 including choroidal abnormalities (CAs), hyperpigmented spots (HSs) and retinal vascular abnormalities (RVAs). Recent advances in multi-modality imaging in ophthalmology have allowed for the improved characterization of these clinical signs. Accordingly, CAs, easily detectable as bright patchy nodules on near-infrared imaging, have recently been added to the revised diagnostic criteria for NF1 due to their high specificity and sensitivity. Furthermore, subclinical alterations of the visual pathways, regardless of the presence of OPGs, have been recently described in NF1, with a primary role of neurofibromin in the myelination process. In this paper, we reviewed the latest progress in the understanding of choroidal and retinal abnormalities in NF1 patients. The clinical significance of the recently revised diagnostic criteria for NF1 is discussed along with new updates in molecular diagnosis. New insights into NF1-related neuro-ophthalmic manifestations are also provided based on electrophysiological and optical coherence tomography (OCT) studies.

The Surprises of Molecular Testing in Neurofibromatosis Type 1: Rare Association between Two Mutational Variants

“…Choroidal abnormalities are more common in adults (80-90%). In children, they occur at a much lower rate (60-78.6%), but compared to Lisch nodules, they are much more common [17,34,36]. The case presented by the authors shows ocular refractive disorders: myopia and astigmatism, respectively Lisch nodules.…”

“…Neurofibromin is a regulator of the RAS/MAPK signaling pathway. If it loses its function, outof-control RAS activity occurs, leading to uncontrolled cell division and the triggering of tumorigenesis by disrupting the cell cycle [17].…”

The Importance of Molecular Testing in Neurofibromatosis Type 1: Rare Association between Two Mutational Variants in NF1 Gene and CRX Gene. Case Report and Short Literature Review

“…Neurofibromin is a regulator of the RAS/MAPK signaling pathway. If it loses its function, outof-control RAS activity occurs, leading to uncontrolled cell division and the triggering of tumorigenesis by disrupting the cell cycle [19].…”