Clinics, Epidemiology and Genetics of Retinitis Pigmentosa

Inherited retinal dystrophies represent the most frequent hereditary disorders of the ocular posterior segment. The chronic eye diseases included in this heterogeneous group of genetic degenerative disorders of the retina are also habitually named retinitis pigmentosa, a term coined by Donders more than 150 years ago. Taking into account all the different forms of retinitis pigmentosa (RP), among the general population, their total prevalence is variably reported in one case for each 2500-7000 persons. In view of that, RP should be labeled as rare or orphan disease even if, for several reasons, it could be considered very atypical within this category of pathologies; firstly given that a worldwide shared consensus on the definition of rare disease does not exist, but also because RP represents one of the most common causes of blindness or severe low-vision in people from 20 to 60 years old. In addition, it is not true that RP is less known or studied than other more frequent eye disorders, and the nearly 7000 references, which appear using " retinitis pigmentosa " in a PubMed search, demonstrate that RP is characterized by a high " desirability " for clinical and experimental researches. On the other hand, it is true that many clinical and welfare problems are common to all RP forms and, above all, that RP requires specific and continuative cares, the fulfillment of which is impossible without a considerable public support participation. Moreover, despite the outstanding scientific advances achieved in the knowledge of RP during the last three decades, evidence-based therapies do not exist for this terrible retinal neuro-degeneration. In other words, RPs are not sufficiently rare as to result in a low research interest, but they are so genotypically intricate and/or phenotypically severe that become very hard to face. At present, the numerous forms of RP are considered the most complex category of retinal diseases. They can be transmitted by all types of monogenic inheritance (autosomal dominant, autosomal recessive, X-linked), even if many cases are diagnosed in patients with no report of affected relatives. These genetic degenerations of the retina are sometimes associated with various non-ocular disorders (syndromic RP), and are characterized by: i) remarkable taxonomic heterogeneity; ii) frequent phenotypic inter-or intra-familial variability; iii) large genotypic multiplicity which becomes more evident examining different ethnic clusters. In fact, although more than 200 causative mutations of RP have been hitherto discovered in more than 100 different genes, the …