Spectrum and frequencies of extraocular features reported in CEP290-associated ciliopathy – A systematic review

Pathogenic variants in the CEP290 gene may result in a broad spectrum of diseases, ranging from lethal neonatal syndromes to isolated retinopathy. A detailed review of the clinical spectrum with the incidence of affected extraocular systems has not yet been published. A review of published papers was carried out to provide a comprehensive report on systemic signs and symptoms associated with CEP290 ciliopathies and to explore the genotype-phenotype correlation. Genetic and clinical data were collected on patients with biallelic variants in the CEP290 gene and the extraocular tissues affected. Genotype-phenotype analysis was performed. Two hundred thirty-five patients were included in the analysis. The most frequently reported organs affected, after the eye, were the central nervous system (82.6%, 194/235), followed by the kidney (53.2%, 125/235), skeletal system (15.3% 36/235), and a large spectrum of other, less frequently reported clinical manifestations. Patients with two variants that together predictably resulted in a low amount of CEP290 protein showed a significant association with having two or more extraocular organ systems affected. This is the most extensive report to date on patients with CEP290-ciliopathy and affected extraocular tissues. Based on these findings and previous publications, systemic screening is proposed, together with a clinical pathway for patients with CEP290-related ciliopathy.