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Abstract Background Syndromic genetic disorders affecting vision can also cause hearing loss, and Usher syndrome is by far the most common etiology. However, many other conditions can present dual sensory impairment. Accurate diagnosis is essential for providing patients with genetic counseling, prognostic information, and appropriate resources. This study aimed to describe the genetic profile of combined inherited deaf-blindness in Portugal. Methods This was a cross-sectional study conducted at a tertiary hospital in Portugal. Patients were identified through the national, web-based inherited retinal dystrophies registry (IRD-PT, retina.com.pt). Demographics, clinical, and genetic data were retrieved from individual patient records. Genetic variants were classified according to the American College of Medical Genetics and Genomics; only likely pathogenic or pathogenic variants were considered relevant for solved cases. Results Eighty-four patients (58.3% males; mean age 40.0 ± 17.9 years) from 71 families were included. Usher syndrome was the most frequent etiology (71.4%) followed by Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract syndrome (6.0%), Autosomal dominant optic atrophy plus (4.8%) and cone-rod dystrophy and hearing loss (4.8%). Other less frequent etiologies included Alport syndrome (2.4%), Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (2.4%), Heimler syndrome (2.4%), Senior-Loken syndrome (1.2%), Waardenburg syndrome (1.2%), Maternally inherited diabetes and deafness (1.2%), and Stickler syndrome (1.2%). The overall diagnostic yield of deleterious variants in our deaf–blind cohort was 73.2%. A total of 55 genetic variants were identified across 16 different genes; 11 of these variants are novel and herein reported for the first time. Conclusions This is the first study to describe the genetic profile of patients with dual sensory impairment in Portugal, highlighting the genetic heterogeneity associated with inherited deaf-blindness. Usher syndrome was the most prevalent cause in this cohort. Nevertheless, several other less frequent causes must also be considered. This study showed a high diagnostic yield and reported 11 novel genetic variants, thereby contributing to expand the mutational spectrum of these conditions.

Abstract Purpose To evaluate self-reported visual function in retinitis pigmentosa (RP) patients with and without cystoid macular edema (CME) and to explore associations between cystoid spaces (CS), retinal morphometric parameters, and clinical data using swept-source optical coherence tomography (SS-OCT). Methods In this cross-sectional case-control study (1:3) conducted at an Inherited Retinal Degenerations referral center in Portugal, RP patients with and without CME (matched for age and gender) completed the Michigan Retinal Degeneration Questionnaire (MRDQ) and underwent SS-OCT. Morphometric analysis, including ellipsoid zone area (EZA), was performed by two independent graders. In the CME group, detailed CS analysis was conducted. Correlations between clinical data - age, gender, best-corrected visual acuity (BCVA) - and MRDQ domains were evaluated. Results The study included 23 RP patients with CME (60.87% male, mean age 44.65 ± 13.58 years) and 69 without CME (49.28% male, mean age 47.94 ± 14.39 years). No significant differences were found between groups in almost all MRDQ domains, BCVA, or EZA. Age positively correlated with 4 MRDQ domains in both groups. BCVA negatively correlated with nearly all MRDQ domains. While EZA showed a negative correlation in both groups, it was significant only in RP without CME. In the CME group, centrally located, outer nuclear layer-involving and large CS were associated with worse BCVA but better EZA. Conclusion MRDQ responses strongly correlated with clinical parameters. CME does not seem to affect self-reported visual function in RP patients, and CS may not worsen visual function. Thus, aggressive treatment of CME in RP may not be necessary.