Alterações genéticas e oftalmológicas na neurofibromatose tipo 2

Abstract

ABSTRACT

Genetic and Ocular Alterations in Neurofibromatosis type 2 Background: Neurofibromatosis type 2 (NF2) is an autosomal-dominant disease, characterized by bilateral vestibular schwannomas, multiple central nervous system (CNS) tumors, skin tumors and juvenile cataract. A well-defined spectrum of ocular features has been specifically associated with NF2. NF2 has a heterogeneous presentation and the disease severity range widely; from a single tumor developed later in life to multiple tumors appearing in the first decade. NF2 disease-causing mutations includes nonsense, splice site and missense mutations. Genotype-phenotype correlations in NF2 have been proposed, with nonsense and frameshift mutations being associated with the most servere clinical presentation. Correlations between truncating mutations and ocular alterations have also been observed. The present study aims to describe ophthalmological and molecular findings in a series of eight patients with a clinical diagnosis of NF2. Methods: Eye examination was performed in 16 NF2 eyes and it included measurement of the visual acuity, biomicroscopy, dilated fundus examination, color fundus photography, infrared photography and spectral domain optical coherence tomography (SD-OCT). Molecular analysis was performed with whole-exome sequencing using DNA derived from peripheral blood mononuclear cells from each individual. Results: Ophthalmological features were observed in all patients, and range widely from subtle retinal alterations identified only by SD-OCT to severe ocular involvement present at birth. Three categories of mutations were found: three patients with premature termination codon (nonsense) mutations, two patients with frameshift mutations and one patient with splice site mutation. Three novel mutations were found. Conclusion: A descriptive study of ocular and molecular characteristics in NF2 patients is of significant value, since there are few previous reports on this subject. The clinical and genetic findings, including three novel mutations add new information on the understanding of genotype-phenotype correlations. Keywords: Epiretinal membrane, Hamartoma, Mutation, Neurofibromatosis type 2, optical coherence tomography, retina, vestibular schwannoma