Author: Margarida Ribeiro (Portugal)
Co-authors: Carla Ferreira, Ana Paula Costa, Paulo Rocha, Fernando Falcão-Reis, Sérgio Estrela Silva
Purpose
Retinitis pigmentosa (RP) is one of the most common hereditary retinal dystrophies. Although genetically and phenotypically heterogeneous, it is typically characterized by a diffuse progressive bilateral dysfunction of predominantly rod photoreceptors with subsequent degeneration of cone photoreceptors and the retinal pigment epithelium. Therefore, this condition evolves into a centripetal, asymmetrical but diffuse pattern. Sector RP is an atypical form of RP that is present in circumscribed areas, usually with bone spicules distribution in the inferior quadrants of the retina. The present study intended to describe clinical, structural and genetic features of a three-generation family composed of three elements with typical RP and one member with sector RP.
Setting/Venue
Description of a familial case series from a single tertiary referral central in Portugal (Department of Ophthalmology of Centro Hospitalar e Universitário São João).
Methods
Four members of a three-generation family underwent ophthalmological examination including best corrected visual acuity (BCVA) and multimodal imaging of structural features with fundus photography, fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD - OCT). Functional evaluation included visual field and electroretinographic testing. All patients underwent genetic testing to identify the molecular etiology of their disease.
Results
All four patients were molecularly confirmed, with identification of a new variant of the RHO gene - c.545G>A[p.(Gly182Asp)], representing a replacement of one amino acid of glycine for an aspartic acid. All members were heterozygous for this autosomal dominant mutation. Among the three patients (from three different generations) with the typical form of RP, it was observed that the oldest family member presented worse BCVA (51 letters oculus dexter (OD) and 48 letters oculus sinister (OS) in the ETDRS score) and more diffuse anatomical, visual field and electroretinographic impairment, with foveal involvement, in comparison to the second (BCVA of 73 letters OD and 83 letters OS and structural and functional involvement into the macular periphery, preserving the fovea) and the third (BCVA of 85 letters OD and OS, no macular involvement) generation members. The patient with sector RP, corresponding to the first member of the second generation, presented a BCVA of 82 letters OD and 72 letters OS, normal electroretinographic findings and visual field and impairment and anatomical findings limited to the inferior and nasal peripheral retina.
Conlusions
To date, this is the first case of a single member with sector RP among a three-generation family with autosomal dominant RP with the same new mutation. This finding supports the well documented clinical heterogeneity for mutations of the same nature. There is a clear gradient of severity according to age and throughout generation, with worse functional and structural outcome in the older member among family members with typical RP. The patient with sector RP presented relatively good outcomes. This three-generation case series reflects the progressive behaviour of RP, with diffuse RP presenting worse outcomes than sectoral RP, an atypical form with slower rate of progression. Althought there is no current treatment, it is important to detect these patients in order to elucidate patients’ expectations and prognosis, provide genetic counseling and inform them of potential participation in the increasing numbers of trials of novel therapeutics and possible access to future treatments.
Financial Disclosure
NONE
Comments
-
