Syndromic hereditary retinal dystrophies are defined by the association of ophthalmological damage with manifestations in one or more other organs, making up a highly heterogeneous group of pathologies on a genetic and biological level. Often regarded as exceptional and anecdotal, scientific work on rare syndromes involving retinal degeneration is, on the contrary, a very important field for gaining a better understanding of retinal physiology and the mechanisms that lead to retinal cell death. Advances in molecular genetics, notably in high-throughput sequencing, and advances in in vitro, in vivo and even in silico modelling , are bringing to light biological pathways that are sometimes unprecedented as being linked to retinal physiology, potentially pointing the way to therapeutic targets.
Various categories of syndromes will be discussed from clinical, biological and pathophysiological angles. First, we'll look at the causes of syndromic retinopathies linked to very general cellular dysfunctions, known as ubiquitous retinopathies, such as the biological pathways linked to DNA repair (i.e. Cockayne syndrome) or to the dysfunction of organelles such as mitochondria, lysosomes or peroxisomes. Secondly, we will look at the categories of syndromes that we call sensory in the broadest sense of the term, applied not only to clinical manifestations, but also to the cellular level. Usher's syndromes will help us to understand a double clinical sensory impairment, while the rapidly expanding group of ciliopathies (i.e.: Bardet-Biedl syndrome, Alström syndrome) will highlight the importance of the primary cilium, the cell's true sensory organelle.
These various syndromes reveal the extreme sensitivity of the photoreceptor cell to disorders of ubiquitous biological pathways, or to very specific pathways such as dysfunction of the connector cilium. These syndromes also underline the extreme diversity of causes of hereditary retinal dystrophies, as well as the need to find therapies to alleviate the visual handicap combined with other, often very severe, handicaps.
