Genotype-phenotype relationship in retinopathy: a perspective from a pediatric age group.

Introduction: Monocentric retrospective case series to describe clinical and molecular peculiarities in a series of pediatric patients in attempting a possible genotype-phenotype correlation.

Methods: We included 13 pediatric patients from 7 unrelated families (ages 1-18) with biallelic pathogenic and likely pathogenic variants in RDH12 gene. For all our patients segregation analyses were performed in their parents and affected siblings. According to their cooperation, patients underwent a complete ophtalmic examination and imaging with full field standard electroretinography (ffERG), spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF).

Results: According to previous studies, we did not observe a conclusive genotype-phenotype correlation in our series, nevertheless we reported 2 new RDH12 likely pathogenic variants. Also, we report clinical data on pediatric patients, with the fundus imaging in the youngest child (2 yo) described in the literature in whom retinal dystrophic changes are already present.

Discussion: This study includes a collection of genotypic and phenotypic data from children with RDH12-associated IRD. These findings will help further characterize RDH12-related retinopathy. Determining the time window of onset of dystrophic changes is critical to research the correct timing for administering possible therapies. More extensive and functional studies are needed in view of the opportunity of gene replacement therapy for RDH12 associated IRD.