Figure 1

Clinical classification of patients with inherited syndromic retinopathies (ISR) and molecular findings obtained in this study. The two charts summarize initial and reassessed clinical classifications, before and after molecular testing, respectively. Four main phenotypic categories of cases were considered: i) clinically-defined ciliopathy syndromes, represented in dark blue color; ii) ciliopathy-like cases, in which retinal degeneration was found in association with multiple ciliopathy-like features (in light blue color); iii) patients with a clear diagnosis of a non-ciliopathy RD, represented in green, and iv) miscellaneous cases (in red color) with a variety of phenotypes that involved RD with one or more unspecific systemic symptoms, in which an obvious diagnosis could not be clearly established. The different levels of circles of the right chart (from inner to outside) reflect molecular yield depending on these 4 clinical categories and the mutated genes. Inner circle in grey shapes represents the fraction of solved (30%, 14/47) vs unsolved (70%, 33/47) cases after molecular testing. Second circle indicates the yield of molecular characterization based on the initial classification. Third level shows the causal genes found in this study and their respective color indicate the associated syndromic retinal disease. Outer level indicated the final classification of the solved cases. *CEP41, USH2A, and VSP13B cases, which were initially included in the miscellanea group, were re-classified after genetic testing. Dual diagnosis of USH2A biallelic pathogenic variants and de novo 17q21.31 mosonomy associated with Usher and Koolen de Vries syndromes, respectively. ALMS: Alström syndrome; BBS: Bardet-Biedl Syndrome; ID: Intellectual Disability; ISR: inherited syndromic retinopathies; RD: Retinal Dystrophy; SLS: Senior-Løcken syndrome; USH: Usher syndrome; ZSSD: Zellweger syndrome spectrum disorder.